A Survey of Parental Perception and Pattern of Action in Response to Influenza-like Illness in Their Children: Including Healthcare Use and Vaccination in Korea

PubMed Central

2017-01-01

Seasonal influenza is a significant cause of morbidity and mortality of children in Korea. However, few data are available on parental perception and action toward childhood influenza. This study aimed to characterize parental perception and patterns of action in response to influenza and influenza-like illnesses (ILIs), including vaccination and healthcare use. This prospective study involved a random survey of parents whose children were aged 6–59 months. The survey was conducted in October 2014. The study included 638 parents of 824 children younger than 6 years. Most parental information of influenza came from mass media (28.2%) and social media (15.5%). The factor that most often motivated parents to vaccinate their children against influenza was promotion of the government or mass media (36.6%). Negative predictors of immunization included safety concerns about influenza vaccination (28.1%) and mistrust in the vaccine's effectiveness (23.3%). Therefore, correct information about influenza and vaccination from mass media will be one of the cornerstones for implementing a successful childhood immunization program and reducing morbidity and mortality in Korea. Furthermore, to enroll younger children in vaccination programs, and to minimize coverage gaps, public concerns about vaccine safety should be resolved. The demographic data in the present study will be used to provide a deeper insight into a parental perception and will help health care providers increase influenza immunization rate. PMID:28049230

Impact of school flu vaccine program on student absences.

PubMed

Plaspohl, Sara S; Dixon, Betty T; Streater, James A; Hausauer, Elizabeth T; Newman, Christopher P; Vogel, Robert L

2014-02-01

Literature provides evidence that school attendance correlates with academic performance and student success. Influenza is a contributing factor to school absences. Primary prevention for influenza includes immunization. School-located influenza vaccine (SLIV) programs provide greater access for students to be immunized. A retrospective review of preexisting data from four academic years was conducted to examine the relationship between SLIV participation and absenteeism among students at eight public elementary schools in Effingham County, Georgia. Results identified differences in average frequency of absences between SLIV and non-SLIV years as well as between SLIV participants and nonparticipants for the 2 SLIV years. Implications for practice include the potential for increased herd immunity among students, which may also extend to other parties within the school community and at home, thus promoting overall wellness and future student success.

Universal Vaccines and Vaccine Platforms to Protect against Influenza Viruses in Humans and Agriculture

PubMed Central

Rajão, Daniela S.; Pérez, Daniel R.

2018-01-01

Influenza virus infections pose a significant threat to public health due to annual seasonal epidemics and occasional pandemics. Influenza is also associated with significant economic losses in animal production. The most effective way to prevent influenza infections is through vaccination. Current vaccine programs rely heavily on the vaccine's ability to stimulate neutralizing antibody responses to the hemagglutinin (HA) protein. One of the biggest challenges to an effective vaccination program lies on the fact that influenza viruses are ever-changing, leading to antigenic drift that results in escape from earlier immune responses. Efforts toward overcoming these challenges aim at improving the strength and/or breadth of the immune response. Novel vaccine technologies, the so-called universal vaccines, focus on stimulating better cross-protection against many or all influenza strains. However, vaccine platforms or manufacturing technologies being tested to improve vaccine efficacy are heterogeneous between different species and/or either tailored for epidemic or pandemic influenza. Here, we discuss current vaccines to protect humans and animals against influenza, highlighting challenges faced to effective and uniform novel vaccination strategies and approaches. PMID:29467737

Economic evaluation of pediatric influenza immunization program compared with other pediatric immunization programs: A systematic review

PubMed Central

Gibson, Edward; Begum, Najida; Sigmundsson, Birgir; Sackeyfio, Alfred; Hackett, Judith; Rajaram, Sankarasubramanian

2016-01-01

ABSTRACT This study compared the economic value of pediatric immunisation programmes for influenza to those for rotavirus (RV), meningococcal disease (MD), pneumococcal disease (PD), human papillomavirus (HPV), hepatitis B (Hep B), and varicella reported in recent (2000 onwards) cost-effectiveness (CE) studies identified in a systematic review of PubMed, health technology, and vaccination databases. The systematic review yielded 51 economic evaluation studies of pediatric immunisation — 10 (20%) for influenza and 41 (80%) for the other selected diseases. The quality of the eligible articles was assessed using Drummond's checklist. Although inherent challenges and limitations exist when comparing economic evaluations of immunisation programmes, an overall comparison of the included studies demonstrated cost-effectiveness/cost saving for influenza from a European-Union-Five (EU5) and United States (US) perspective; point estimates for cost/quality-adjusted life-years (QALY) from dominance (cost-saving with more effect) to ≤45,444 were reported. The economic value of influenza programmes was comparable to the other vaccines of interest, with cost/QALY in general considerably lower than RV, Hep B, MD and PD. Independent of the perspective and type of analysis, the economic impact of a pediatric influenza immunisation program was influenced by vaccine efficacy, immunisation coverage, costs, and most significantly by herd immunity. This review suggests that pediatric influenza immunisation may offer a cost effective strategy when compared with HPV and varicella and possibly more value compared with other childhood vaccines (RV, Hep B, MD and PD). PMID:26837602

Economic evaluation of pediatric influenza immunization program compared with other pediatric immunization programs: A systematic review.

PubMed

Gibson, Edward; Begum, Najida; Sigmundsson, Birgir; Sackeyfio, Alfred; Hackett, Judith; Rajaram, Sankarasubramanian

2016-05-03

This study compared the economic value of pediatric immunisation programmes for influenza to those for rotavirus (RV), meningococcal disease (MD), pneumococcal disease (PD), human papillomavirus (HPV), hepatitis B (Hep B), and varicella reported in recent (2000 onwards) cost-effectiveness (CE) studies identified in a systematic review of PubMed, health technology, and vaccination databases. The systematic review yielded 51 economic evaluation studies of pediatric immunisation - 10 (20%) for influenza and 41 (80%) for the other selected diseases. The quality of the eligible articles was assessed using Drummond's checklist. Although inherent challenges and limitations exist when comparing economic evaluations of immunisation programmes, an overall comparison of the included studies demonstrated cost-effectiveness/cost saving for influenza from a European-Union-Five (EU5) and United States (US) perspective; point estimates for cost/quality-adjusted life-years (QALY) from dominance (cost-saving with more effect) to ≤45,444 were reported. The economic value of influenza programmes was comparable to the other vaccines of interest, with cost/QALY in general considerably lower than RV, Hep B, MD and PD. Independent of the perspective and type of analysis, the economic impact of a pediatric influenza immunisation program was influenced by vaccine efficacy, immunisation coverage, costs, and most significantly by herd immunity. This review suggests that pediatric influenza immunisation may offer a cost effective strategy when compared with HPV and varicella and possibly more value compared with other childhood vaccines (RV, Hep B, MD and PD).

Biomimetic Antigenic Nanoparticles Elicit Controlled Protective Immune Response to Influenza

PubMed Central

Patterson, Dustin P.; Rynda-Apple, Agnieszka; Harmsen, Ann L.; Harmsen, Allen G.; Douglas, Trevor

2013-01-01

Here we present a biomimetic strategy towards nanoparticle design for controlled immune response through encapsulation of conserved internal influenza proteins on the interior of virus like particles (VLPs) to direct CD8+ cytotoxic T cell protection. Programmed encapsulation and sequestration of the conserved nucleoprotein (NP) from influenza on the interior of a VLP, derived from the bacteriophage P22, results in a vaccine that provides multi-strain protection against 100 times lethal doses of influenza in an NP specific CD8+ T cell-dependent manner. VLP assembly and encapsulation of the immunogenic NP cargo protein is the result of a genetically programmed self-assembly making this strategy amendable to the quick production of vaccines to rapidly emerging pathogens. Addition of adjuvants or targeting molecules were not required for eliciting the protective response. PMID:23540530

Use of Seasonal Influenza Vaccination and Its Associated Factors among Elderly People with Disabilities in Taiwan: A Population-Based Study.

PubMed

Chang, Yu-Chia; Tung, Ho-Jui; Hsu, Shang-Wei; Chen, Lei-Shin; Kung, Pei-Tseng; Huang, Kuang-Hua; Chiou, Shang-Jyh; Tsai, Wen-Chen

2016-01-01

Influenza immunization among elderly people with disabilities is a critical public health concern; however, few studies have examined the factors associated with vaccination rates in non-Western societies. By linking the National Disability Registration System and health service claims dataset from the National Health Insurance program, this population-based study investigated the seasonal influenza vaccination rate among elderly people with disabilities in Taiwan (N = 283,172) in 2008. A multivariate logistic regression analysis was conducted to adjust for covariates. Nationally, only 32.7% of Taiwanese elderly people with disabilities received influenza vaccination. The strongest predictor for getting vaccinated among older Taiwanese people with disabilities was their experience of receiving an influenza vaccination in the previous year (adjusted odds ratio [AOR] = 6.80, 95% confidence interval [CI]: 6.67-6.93). Frequent OPD use (AOR = 1.85, 95% CI: 1.81-1.89) and undergoing health examinations in the previous year (AOR = 1.66, 95% CI: 1.62-1.69) also showed a moderate and significant association with receiving an influenza vaccination. Although free influenza vaccination has been provided in Taiwan since 2001, influenza immunization rates among elderly people with disabilities remain low. Policy initiatives are required to address the identified factors for improving influenza immunization rates among elderly people with disabilities.

Prevention and control of seasonal influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices--United States, 2013-2014.

PubMed

2013-09-20

This report updates the 2012 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccines for the prevention and control of seasonal influenza (CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2012;61:613-8). Routine annual influenza vaccination is recommended for all persons aged ≥ 6 months. For the 2013-14 influenza season, it is expected that trivalent live attenuated influenza vaccine (LAIV3) will be replaced by a quadrivalent LAIV formulation (LAIV4). Inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Vaccine virus strains included in the 2013-14 U.S. trivalent influenza vaccines will be an A/California/7/2009 (H1N1)-like virus, an H3N2 virus antigenically like the cell-propagated prototype virus A/Victoria/361/2011, and a B/Massachusetts/2/2012-like virus. Quadrivalent vaccines will include an additional influenza B virus strain, a B/Brisbane/60/2008-like virus, intended to ensure that both influenza B virus antigenic lineages (Victoria and Yamagata) are included in the vaccine. This report describes recently approved vaccines, including LAIV4, IIV4, trivalent cell culture-based inactivated influenza vaccine (ccIIV3), and trivalent recombinant influenza vaccine (RIV3). No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one product is otherwise appropriate. This information is intended for vaccination providers, immunization program personnel, and public health personnel. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates also will be found at this website. Vaccination and health-care providers should check the CDC influenza website periodically for additional information.

Is performance of influenza vaccination in the elderly related to treating physician's self immunization and other physician characteristics?

PubMed

Abramson, Zvi Howard; Levi, Orit

2008-11-01

Studies have demonstrated associations between physicians' characteristics, specifically personal health behavior, and their reported prevention counseling behavior. This study, performed in 2007, examines associations between patients getting immunized against influenza and characteristics of their primary care physicians, including whether they themselves were immunized. Computerized data were extracted on 29,447 patients aged 65 years and over registered in the largest health maintenance organization (HMO) in the Jerusalem area and on their primary care physicians. Further physician data were collected from a questionnaire distributed to a large sample of physicians. Logistic regression was performed with patient immunization as the dependent variable. Patients were more likely to get vaccinated if their physician was vaccinated and if the physician was female or a specialist or had studied in West Europe or America. Patients of physicians who reported exercising regularly and of physicians who knew that the vaccine can't cause influenza were also more likely to get immunized. These associations of physician factors with patient immunization, though statistically significant, were weaker than those previously reported with physician influenza vaccination counseling. Physician's beliefs and medical education and personal health behavior are of importance in determining patient vaccination. An increase in population immunization rates may possibly be achieved by programs directed at enhancing physician knowledge and self immunization.

Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic

PubMed Central

Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M. Carolina; Ruiz-Matus, Cuauhtémoc

2016-01-01

ABSTRACT Background: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. Methods: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Results: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6–23 months, 32% of children aged 5–2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013–14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the review of national evidence. LAC countries have also established an official network dedicated to evaluating influenza vaccines effectiveness and impact. Conclusion: Following the A(H1N1)2009 influenza pandemic, countries of the Americas have continued their efforts to sustain or increase seasonal influenza vaccine uptake among high risk groups, especially among pregnant women. Countries also continued strengthening influenza surveillance, immunization platforms and information systems, indirectly improving preparedness for future pandemics. Influenza vaccination is particularly challenging compared to other vaccines included in EPI schedules, due to the need for annual, optimally timed vaccination, the wide spectrum of target groups, and the limitations of the available vaccines. Countries should continue to monitor influenza vaccination coverage, generate evidence for vaccination programs and implement social communication strategies addressing existing gaps. PMID:27196006

Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic.

PubMed

Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M Carolina; Ruiz-Matus, Cuauhtémoc

2016-08-02

There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6-23 months, 32% of children aged 5-2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013-14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the review of national evidence. LAC countries have also established an official network dedicated to evaluating influenza vaccines effectiveness and impact. Following the A(H1N1)2009 influenza pandemic, countries of the Americas have continued their efforts to sustain or increase seasonal influenza vaccine uptake among high risk groups, especially among pregnant women. Countries also continued strengthening influenza surveillance, immunization platforms and information systems, indirectly improving preparedness for future pandemics. Influenza vaccination is particularly challenging compared to other vaccines included in EPI schedules, due to the need for annual, optimally timed vaccination, the wide spectrum of target groups, and the limitations of the available vaccines. Countries should continue to monitor influenza vaccination coverage, generate evidence for vaccination programs and implement social communication strategies addressing existing gaps.

Factors associated with differential uptake of seasonal influenza immunizations among underserved communities during the 2009-2010 influenza season.

PubMed

Vlahov, David; Bond, Keosha T; Jones, Kandice C; Ompad, Danielle C

2012-04-01

Influenza vaccination coverage remains low and disparities persist. In New York City, a community-based participatory research project (Project VIVA) worked to address this issue in Harlem and the South Bronx by supplementing existing vaccination programs with non-traditional venues (i.e., community-based organizations). We conducted a 10 min survey to assess access to influenza vaccine as well as attitudes and beliefs towards influenza vaccination that could inform intervention development for subsequent seasons. Among 991 participants recruited using street intercept techniques, 63% received seasonal vaccine only, 11% seasonal and H1N1, and 26% neither; 89% reported seeing a health care provider (HCP) during the influenza season. Correlates of immunization among those with provider visits during the influenza season included being US-born, interest in getting the vaccine, concern about self or family getting influenza, an HCP's recommendation and comfort with government. Among those without an HCP visit, factors associated with immunization included being US born, married, interest in getting the vaccine, understanding influenza information, and concern about getting influenza. Factors associated with lack of interest in influenza vaccine included being born outside the US, Black and uncomfortable with government. In medically underserved areas, having access to routine medical care and understanding the medical implications of influenza play an important role in enhancing uptake of seasonal influenza vaccination. Strategies to improve vaccination rates among Blacks and foreign-born residents need to be addressed. The use of non-traditional venues to provide influenza vaccinations in underserved communities has the potential to reduce health disparities.

Health care worker influenza immunization rates: the missing pieces of the puzzle.

PubMed

Quach, Susan; Pereira, Jennifer A; Heidebrecht, Christine L; Kwong, Jeffrey C; Guay, Maryse; Crowe, Lois; Quan, Sherman; Bettinger, Julie A

2013-08-01

Immunization rates are used to assess the level of protection against influenza, but limited data exist on how such rates are measured in health care organizations. We conducted key informant interviews with campaign planners to learn about processes for collecting immunization data, including barriers and facilitating factors for measuring and reporting rates. We conducted telephone interviews with 23 influenza immunization program planners across Canada working in 7 acute care hospitals, 6 continuing care facilities, and 8 public health organizations in 2012. We used content analysis to examine the interview data. The methods used to collect immunization data varied by the size and type of health care organization. Immunization data from different personnel groups were included in immunization rate calculations depending on the local public health reporting requirements and the organization's size. Challenges associated with collecting immunization data and calculating rates included lack of resources for identifying personnel immunized off-site, tracking personnel who declined immunization, identifying non-payroll staff, and interpreting unclear public health reporting requirements. Support from other vaccine providers, public health, employers, and professional and external bodies is needed to provide the necessary information and resources to calculate accurate and complete rates. Further work is needed to refine and standardize the collection of HCW influenza immunization data so that it may be used for surveillance and quality assessment purposes. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Benefits and Effectiveness of Administering Pneumococcal Polysaccharide Vaccine With Seasonal Influenza Vaccine: An Approach for Policymakers

PubMed Central

Nanni, Angeline; Levine, Orin

2012-01-01

For the influenza pandemic of 2009–2010, countries responded to the direct threat of influenza but may have missed opportunities and strategies to limit secondary pneumococcal infections. Delivering both vaccines together can potentially increase pneumococcal polysaccharide vaccine (PPV23) immunization rates and prevent additional hospitalizations and mortality in the elderly and other high-risk groups. We used PubMed to review the literature on the concomitant use of PPV23 with seasonal influenza vaccines. Eight of 9 clinical studies found that a concomitant program conferred clinical benefits. The 2 studies that compared the cost-effectiveness of different strategies found concomitant immunization to be more cost-effective than either vaccine given alone. Policymakers should consider a stepwise strategy to reduce the burden of secondary pneumococcal infections during seasonal and pandemic influenza outbreaks. PMID:22397339

Influenza vaccination coverage among US children from 2004/2005 to 2015/2016.

PubMed

Tian, Changwei; Wang, Hua; Wang, Wenming; Luo, Xiaoming

2018-05-15

Quantify the influenza vaccine coverage is essential to identify emerging concerns and to immunization programs for targeting interventions. Data from National Health Interview Survey were used to estimate receipt of at least one dose of influenza vaccination among children 6 months to 17 years of age. Influenza vaccination coverage increased from 16.70% during 2004/2005 to 49.43% during 2015/2016 (3.18% per year, P < 0.001); however, the coverage increased slightly after 2010/2011. Children at high risk of influenza complications had higher influenza vaccination coverage than non at-risk children. Boys and girls had similar coverage each year. While the coverage increased from 2004/2005 to 2015/2016 for all age groups, the coverage decreased with age each year (-0.64 to -1.58% per age group). There was a higher and rapid increase of coverage in Northeast than Midwest, South and West. American Indian or Alaskan Native and Asian showed higher coverage than other race groups (White, Black/African American, Multiple race). Multivariable analysis showed that high-risk status and region had the greatest associations with levels of vaccine coverage. Although the influenza vaccination coverage among children had increased remarkably since 2004/2005, establishing more effective immunization programs are warranted to achieve the Healthy People 2020 target.

Translating vaccine policy into action: a report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings.

PubMed

Ortiz, Justin R; Neuzil, Kathleen M; Ahonkhai, Vincent I; Gellin, Bruce G; Salisbury, David M; Read, Jennifer S; Adegbola, Richard A; Abramson, Jon S

2012-11-26

Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life. In April 2012, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended revisions to the WHO position paper on influenza vaccines. For the first time, SAGE recommended pregnant women should be made the highest priority for inactivated seasonal influenza vaccination. However, the variable maternal influenza vaccination coverage in countries with pre-existing maternal influenza vaccine recommendations underscores the need to understand and to address the discrepancy between recommendations and implementation success. We present the outcome of a multi-stakeholder expert consultation on inactivated influenza vaccination in pregnancy. The creation and implementation of vaccine policies and regulations require substantial resources and capacity. As with all public health interventions, the existence of perceived and real risks of vaccination will necessitate effective and transparent risk communication. Potential risk allocation and sharing mechanisms should be addressed by governments, vaccine manufacturers, and other stakeholders. In resource-limited settings, vaccine-related issues concerning supply, formulation, regulation, evidence evaluation, distribution, cost-utility, and post-marketing safety surveillance need to be addressed. Lessons can be learned from the Maternal and Neonatal Tetanus Elimination Initiative as well as efforts to increase vaccine coverage among pregnant women during the 2009 influenza pandemic. We conclude with an analysis of data gaps and necessary activities to facilitate implementation of maternal influenza immunization programs in resource-limited settings. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

Impact of pharmacists providing immunizations on adolescent influenza immunization.

PubMed

Robison, Steve G

2016-01-01

To determine if the Oregon law change in 2011 to allow pharmacists to immunize adolescents 11 to 17 years of age increased influenza immunizations or changed existing immunization venues. With the use of Oregon's ALERT Immunization Information System (IIS), 2 measures of impact were developed. First, the change in adolescent age 11-17 influenza immunizations before (2007-2010) and after (2011-2014) the pharmacy law change was evaluated against a reference cohort (aged 7-10) not affected by the law. Community pharmacies were also compared with other types of influenza immunization sites within one of the study influenza seasons (2013-2014). From 2007 to 2014, adolescent influenza immunizations at community pharmacies increased from 36 to 6372 per year. After the 2011 pharmacy law change, adolescents aged 11 to 17 were more likely to receive an influenza immunization compared with the reference population (odds ratio, 1.21; 95% CI, 1.19-1.22). Analysis of the 2013-2014 influenza season suggests that community pharmacies immunized a different population of adolescents than other providers. The 2011 change in Oregon law allowed pharmacists to increase the total of influenza immunizations given to adolescents. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

How rural and urban parents describe convenience in the context of school-based influenza vaccination: a qualitative study.

PubMed

Lind, Candace; Russell, Margaret L; Collins, Ramona; MacDonald, Judy; Frank, Christine J; Davis, Amy E

2015-01-22

Seasonal influenza vaccine uptake among school-age children has been low, particularly among rural children, even in jurisdictions in Canada where this immunization is publicly funded. Providing this vaccination at school may be convenient for parents and might contribute to increased vaccine uptake, particularly among rural children. We explore the construct of convenience as an advantage of school based influenza vaccination. We also explore for rural urban differences in this construct. Participants were parents of school-aged children from Alberta, Canada. We qualitatively analyzed focus group data from rural parents using a thematic template that emerged from prior work with urban parents. Both groups of parents had participated in focus groups to explore their perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools. Data from within the theme of 'convenience' from both rural and urban parents were then further explored for sub-themes within convenience. Data were obtained from nine rural and nine urban focus groups. The template of themes that had arisen from prior analysis of the urban data applied to the rural data. Convenience was a third level theme under Advantages. Five fourth level themes emerged from within convenience. Four of the five sub-themes were common to both rural and urban participants: reduction of parental burden to schedule, reduction in parental lost time, decrease in parental stress and increase in physical access points for influenza immunization. The fifth subtheme, increases temporal access to influenza immunization, emerged uniquely from the rural data. Both rural and urban parents perceived that convenience would be an advantage of adding an annual influenza immunization to the vaccinations currently given to Alberta children at school. Improving temporal access to such immunization may be a more relevant aspect of convenience to rural than to urban parents.

Naturally Acquired and Conjugate Vaccine-Induced Antibody to Haemophilus influenzae Type b (Hib) Polysaccharide in Malian Children: Serological Assessment of the Hib Immunization Program in Mali

PubMed Central

Hutter, Julia; Pasetti, Marcela F.; Sanogo, Doh; Tapia, Milagritos D.; Sow, Samba O.; Levine, Myron M.

2012-01-01

Haemophilus influenzae type b (Hib) conjugate vaccine for infants (6, 10, and 14 weeks of age) was introduced into the Malian Expanded Program on Immunization in July 2005, to diminish invasive Hib disease in young children. Antibodies to Hib capsular polysaccharide (PRP) were measured in infants and toddlers from an area already served by the Hib immunization program (Bamako) and in unimmunized children of the same age in a district (Kangaba) where Hib immunization had not yet begun. Among vaccinated Bamako children 6–23 months of age, 77–93% exhibited PRP titers ≥ 1.0 μg/mL, indicating long-term protection, versus only 10–23% of Kangaba children of that age. High PRP antibody titers in immunized children persisted through 2 years of age. Moreover, ∼50% of Bamako children exhibited anti-PRP titers ≥ 5.0 μg/mL; a level that impedes Hib upper respiratory carriage, and may thereby diminish the Hib transmission to the unimmunized susceptible population (i.e., providing indirect protection). PMID:22665612

Impact of Pharmacist Immunization Authority on Seasonal Influenza Immunization Rates Across States.

PubMed

Drozd, Edward M; Miller, Laura; Johnsrud, Michael

2017-08-01

The goal of this study was to investigate the impact on immunization rates of policy changes that allowed pharmacists to administer influenza immunizations across the United States. Influenza immunization rates across states were compared before and after policy changes permitting pharmacists to administer influenza immunizations. The study used Behavioral Risk Factor Surveillance System (BRFSS) survey data on influenza immunization rates between 2003 and 2013. Logistic regression models were constructed and incorporated adjustments for the complex sample design of the BRFSS to predict the likelihood of a person receiving an influenza immunization based on various patient health, demographic, and access to care factors. Overall, as states moved to allow pharmacists to administer influenza immunizations, the odds that an adult resident received an influenza immunization rose, with the effect increasing over time. The average percentage of people receiving influenza immunizations in states was 35.1%, rising from 32.2% in 2003 to 40.3% in 2013. The policy changes were associated with a long-term increase of 2.2% to 7.6% in the number of adults aged 25 to 59 years receiving an influenza immunization (largest for those aged 35-39 years) and no significant change for those younger or older. These findings suggest that pharmacies and other nontraditional settings may offer accessible venues for patients when implementing other public health initiatives. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

How Influenza Vaccination Policy May affect Vaccine Logistics

PubMed Central

Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Welling, Joel S.; Norman, Bryan A.; Connor, Diana L.; Chen, Sheng-I; Slayton, Rachel B.; Laosiritaworn, Yongjua; Wateska, Angela R.; Wisniewski, Stephen R.; Lee, Bruce Y.

2012-01-01

Background When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Purpose Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. Methods Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand., A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Results Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time - frame from 1 to 6 months decreases these bottlenecks. Conclusion Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. PMID:22537993

Dentists' awareness toward vaccine preventable diseases.

PubMed

Petti, Stefano; Messano, Giuseppe A; Polimeni, Antonella

2011-10-19

Effective infection control in dentistry is unfeasible without an adequate immunization program for dental health care providers (DHCPs). Such an assumption is demonstrated for some vaccine preventable infectious diseases (VPIDs), such as Hepatitis B, Influenza and Varicella. However, excluding Hepatitis B vaccine, immunization programs for DHCPs are few and often unclear about which vaccinations are recommended, thus leading to generally low awareness and consequent low vaccination rates. This survey investigated dentists' awareness toward VPIDs. At the moment of registration to a dental congress, a questionnaire regarding the immunization status toward VPIDs was anonymously filled in by 379 Italian dentists (86% of the contacted dentists), with at least fifteen years of activity. DHCP specific awareness was considered high if dentists reported to have controlled the serum level of anti-HBs during the last ten years and have received seasonal influenza vaccine annually. Awareness toward VPIDs was classified high if dentists reported to be immune against six or seven of the following VIPDs, Hepatitis B, Influenza, Varicella, Measles, Mumps, Rubella and Tetanus. DHCP specific awareness resulted high for 32.5% of subjects and low for 31.1%. None of the subjects reported high awareness toward VPIDs, while for 60% of them, such awareness was low (immunization status reported for none or one of the seven VPIDs). Low dentists' awareness stresses the need for a transparent immunization program which is effective in controlling VPID transmission in the dental health care settings and focuses on those VPIDs which pose a true risk of infection for DHCPs and patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of a Pharmacy Technician-Driven Program to Improve Vaccination Rates at an Academic Medical Center.

PubMed

Hill, John D; Anderegg, Sammuel V; Couldry, Rick J

2017-10-01

Background: Influenza and pneumococcal disease contribute substantially to the burden of preventable disease in the United States. Despite quality measures tied to immunization rates, health systems have struggled to achieve these targets in the inpatient setting. Pharmacy departments have had success through implementation of pharmacist standing order programs (SOP); however, these initiatives are labor-intensive and have not resulted in 100% immunization rates. Objective: The objective of this study was to evaluate a pilot utilizing pharmacy technician interventions, in combination with a nursing SOP, to improve vaccination rates of hospitalized patients for influenza and pneumococcal disease. Methods: A process was developed for pharmacy technicians to identify patients who were not previously screened or immunized during the weekend days on the Cardiovascular Progressive Care unit at the University of Kansas Health-System. Targeted pharmacy technician interventions consisted of phone call reminders and face-to-face discussions with nursing staff. The primary study outcome was the change in immunization compliance rates between the control and intervention groups. Results: Influenza vaccine rates showed a statistically significant increase from 72.2% (52 of 72) of patients during the control group to 92.9% (65 of 70, P = .001) of patients during the intervention group. A pneumococcal vaccination rate of 81.3% (61 of 75) was observed in the control group, compared with 84.3% (59 of 70) of patients in the intervention group ( P = .638). Conclusion: An improvement in inpatient influenza immunization rates can be achieved through targeted follow-up performed by pharmacy technicians, in combination with a nursing-driven SOP.

Invited Commentary: Influenza, Influenza Immunization, and Pregnancy—It's About Time

PubMed Central

Hutcheon, Jennifer A.; Savitz, David A.

2016-01-01

Immunization of pregnant women against influenza has the potential to reduce adverse fetal outcomes by reducing prenatal exposure to influenza illness. However, as touched on by Fell et al. (Am J Epidemiol. 2016;184(3):163–175) and Vazquez-Benitez et al. (Am J Epidemiol. 2016;184(3):176–186) in this issue of the Journal, observational studies in which the causal effect of maternal influenza illness and influenza immunization on fetal health are evaluated are prone to bias because of the complex temporal nature of influenza illness seasonality, influenza immunization schedules, and gestation itself. Immortal time bias is introduced by an “anytime-in-pregnancy” exposure definition because the shortened pregnancy duration associated with many adverse fetal outcomes limits the opportunity to become exposed, whereas including follow-up time during which pregnancies are no longer at risk of an adverse outcome (e.g., gestational time after 37 weeks in studies of preterm birth) can lead to overestimation of any true benefits of immunization (or harms from influenza illness). We present a framework to avoid time-related biases in the study of influenza illness and immunization in pregnancy and advise that investigations of fetal benefit from maternal influenza immunization should only be undertaken when information is available on the calendar time of influenza virus circulation and the gestational age at which maternal influenza immunization occurred. PMID:27449413

Cost analysis of public health influenza vaccine clinics in Ontario.

PubMed

Mercer, Nicola J

2009-01-01

Public health in Ontario delivers, promotes and provides each fall the universal influenza immunization program. This paper addresses the question of whether Ontario public health agencies are able to provide the influenza immunization program within the Ministry of Health fiscal funding envelope of $5 per dose. Actual program delivery data from the 2006 influenza season of Wellington-Dufferin-Guelph Public Health (WDGPH) were used to create a model template for influenza clinics capturing all variable costs. Promotional and administrative costs were separated from clinic costs. Maximum staff workloads were estimated. Vaccine clinics were delivered by public health staff in accordance with standard vaccine administration practices. The most significant economic variables for influenza clinics are labour costs and number of vaccines given per nurse per hour. The cost of facility rental was the only other significant cost driver. The ability of influenza clinics to break even depended on the ability to manage these cost drivers. At WDGPH, weekday flu clinics required the number of vaccines per nurse per hour to exceed 15, and for weekend flu clinics this number was greater than 21. We estimate that 20 vaccines per hour is at the limit of a safe workload over several hours. Managing cost then depends on minimizing hourly labour costs. The results of this analysis suggest that by managing the labour costs along with planning the volume of patients and avoiding expensive facilities, flu clinics can just break even. However, any increased costs, including negotiated wage increases or the move to safety needles, with a fixed revenue of $5.00 per dose will negate this conclusion.

Universal immunity to influenza must outwit immune evasion

PubMed Central

Quiñones-Parra, Sergio; Loh, Liyen; Brown, Lorena E.; Kedzierska, Katherine; Valkenburg, Sophie A.

2014-01-01

Although an influenza vaccine has been available for 70 years, influenza virus still causes seasonal epidemics and worldwide pandemics. Currently available vaccines elicit strain-specific antibody (Ab) responses to the surface haemagglutinin (HA) and neuraminidase (NA) proteins, but these can be ineffective against serologically-distinct viral variants and novel subtypes. Thus, there is a great need for cross-protective or “universal” influenza vaccines to overcome the necessity for annual immunization against seasonal influenza and to provide immunity to reduce the severity of infection with pandemic or outbreak viruses. It is well established that natural influenza infection can provide cross-reactive immunity that can reduce the impact of infection with distinct influenza type A strains and subtypes, including H1N1, H3N2, H2N2, H5N1, and H7N9. The key to generating universal influenza immunity through vaccination is to target functionally-conserved regions of the virus, which include epitopes on the internal proteins for cross-reactive T cell immunity or on the HA stem for broadly reactive Ab responses. In the wake of the 2009 H1N1 pandemic, broadly neutralizing antibodies (bnAbs) have been characterized and isolated from convalescent and vaccinated individuals, inspiring development of new vaccination techniques to elicit such responses. Induction of influenza-specific T cell responses through vaccination has also been recently examined in clinical trials. Strong evidence is available from human and animal models of influenza to show that established influenza-specific T cell memory can reduce viral shedding and symptom severity. However, the published evidence also shows that CD8+ T cells can efficiently select immune escape mutants early after influenza virus infection. Here, we discuss universal immunity to influenza viruses mediated by both cross-reactive T cells and Abs, the mechanisms of immune evasion in influenza, and propose how to counteract commonly occurring immune-escape variants. PMID:24971078

Influenza Research Database: an integrated bioinformatics resource for influenza research and surveillance

PubMed Central

Squires, R. Burke; Noronha, Jyothi; Hunt, Victoria; García‐Sastre, Adolfo; Macken, Catherine; Baumgarth, Nicole; Suarez, David; Pickett, Brett E.; Zhang, Yun; Larsen, Christopher N.; Ramsey, Alvin; Zhou, Liwei; Zaremba, Sam; Kumar, Sanjeev; Deitrich, Jon; Klem, Edward; Scheuermann, Richard H.

2012-01-01

Please cite this paper as: Squires et al. (2012) Influenza research database: an integrated bioinformatics resource for influenza research and surveillance. Influenza and Other Respiratory Viruses 6(6), 404–416. Background  The recent emergence of the 2009 pandemic influenza A/H1N1 virus has highlighted the value of free and open access to influenza virus genome sequence data integrated with information about other important virus characteristics. Design  The Influenza Research Database (IRD, http://www.fludb.org) is a free, open, publicly‐accessible resource funded by the U.S. National Institute of Allergy and Infectious Diseases through the Bioinformatics Resource Centers program. IRD provides a comprehensive, integrated database and analysis resource for influenza sequence, surveillance, and research data, including user‐friendly interfaces for data retrieval, visualization and comparative genomics analysis, together with personal log in‐protected ‘workbench’ spaces for saving data sets and analysis results. IRD integrates genomic, proteomic, immune epitope, and surveillance data from a variety of sources, including public databases, computational algorithms, external research groups, and the scientific literature. Results  To demonstrate the utility of the data and analysis tools available in IRD, two scientific use cases are presented. A comparison of hemagglutinin sequence conservation and epitope coverage information revealed highly conserved protein regions that can be recognized by the human adaptive immune system as possible targets for inducing cross‐protective immunity. Phylogenetic and geospatial analysis of sequences from wild bird surveillance samples revealed a possible evolutionary connection between influenza virus from Delaware Bay shorebirds and Alberta ducks. Conclusions  The IRD provides a wealth of integrated data and information about influenza virus to support research of the genetic determinants dictating virus pathogenicity, host range restriction and transmission, and to facilitate development of vaccines, diagnostics, and therapeutics. PMID:22260278

Influenza immunization and subsequent diagnoses of group A streptococcus-illnesses among U.S. Army trainees, 2002-2006.

PubMed

Lee, Seung-eun; Eick, Angelia; Bloom, Michael S; Brundage, John F

2008-06-25

To assess the association between influenza immunization and subsequent diagnosis of group A streptococcus (GAS)-illness in Army recruits during influenza seasons 2002-2006. A case-control study was employed with cases as trainees with outpatient GAS diagnosis (ICD-9-CM codes: 034.0, 035, 038.0, 041.01, 320.2, 390-392, 482.31) during the influenza season, and controls as trainees with no outpatient GAS diagnosis during the influenza season. Primary exposure was influenza immunization during 1st September to 30th April of each season. Estimated protective effects of influenza immunization against GAS-illness ranged from 50% to 77%. A strong protective effect was suggested for Army trainee influenza immunization on the diagnosis of GAS-illness.

Report of the WHO technical consultation on the effect of maternal influenza and influenza vaccination on the developing fetus: Montreal, Canada, September 30-October 1, 2015.

PubMed

Fell, Deshayne B; Bhutta, Zulfiqar A; Hutcheon, Jennifer A; Karron, Ruth A; Knight, Marian; Kramer, Michael S; Monto, Arnold S; Swamy, Geeta K; Ortiz, Justin R; Savitz, David A

2017-04-25

In 2012, the World Health Organization (WHO) released a position paper on influenza vaccination recommending that pregnant women have the highest priority for seasonal vaccination in countries where the initiation or expansion of influenza immunization programs is under consideration. Although the primary goal of the WHO recommendation is to prevent influenza illness in pregnant women, the potential benefits of maternal immunization in protecting young infants are also recognized. The extent to which maternal influenza vaccination may prevent adverse birth outcomes such as preterm birth or small-for-gestational-age birth, however, is unclear as available studies are in disagreement. To inform WHO about the empirical evidence relating to possible benefits of influenza vaccination on birth outcomes, a consultation of experts was held in Montreal, Canada, September 30-October 1, 2015. Presentations and discussions covered a broad range of issues, including influenza virus infection during pregnancy and its effect on the health of the mother and the fetus, possible biological mechanisms for adverse birth outcomes following maternal influenza illness, evidence on birth outcomes following influenza illness during pregnancy, evidence from both observational studies and randomized controlled trials on birth outcomes following influenza vaccination of pregnant women, and methodological issues. This report provides an overview of the presentations, discussions and conclusions. Copyright © 2017.

Influenza immunization during pregnancy: Benefits for mother and infant

PubMed Central

Sakala, Isaac G.; Honda-Okubo, Yoshikazu; Fung, Johnson; Petrovsky, Nikolai

2016-01-01

ABSTRACT The serious consequences of influenza infection during pregnancy have been recognized for almost a century. In this article, we reviewed the evidence on the immunogenicity, safety and impact of maternal influenza immunization for both mother and child. After vaccination, pregnant women have similar protective titers of anti-influenza antibodies as non-pregnant women, demonstrating that pregnancy does not alter the trivalent inactivated influenza vaccine immune response. Studies from the United States, Europe and resource-constrained regions demonstrate that maternal vaccination is associated with increased anti-influenza antibody concentrations and protection in the newborn child as well as the immunized mother. Given the acceptable safety profile of influenza vaccines and the World Health Organization's recommendation for its use in pregnant women, maternal vaccination with inactivated influenza vaccine is a cost-effective approach to decrease influenza disease in newborns. However, as seen for influenza immunization in the elderly, the protective efficacy of current inactivated vaccines in protection of newborns is 50% at best, indicating significant room for vaccine improvement, which could potentially be achieved by addition of a safe and effective adjuvant. Thus, global deployment of inactivated influenza immunization during pregnancy would have substantial and measurable health benefits for mothers and their newborns. PMID:27494630

Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses

PubMed Central

van de Sandt, Carolien E.; Kreijtz, Joost H. C. M.; Rimmelzwaan, Guus F.

2012-01-01

The influenza A virus is one of the leading causes of respiratory tract infections in humans. Upon infection with an influenza A virus, both innate and adaptive immune responses are induced. Here we discuss various strategies used by influenza A viruses to evade innate immune responses and recognition by components of the humoral and cellular immune response, which consequently may result in reduced clearing of the virus and virus-infected cells. Finally, we discuss how the current knowledge about immune evasion can be used to improve influenza A vaccination strategies. PMID:23170167

Prolonged protection against Intranasal challenge with influenza virus following systemic immunization or combinations of mucosal and systemic immunizations with a heat-labile toxin mutant.

PubMed

Zhou, Fengmin; Goodsell, Amanda; Uematsu, Yasushi; Vajdy, Michael

2009-04-01

Seasonal influenza virus infections cause considerable morbidity and mortality in the world, and there is a serious threat of a pandemic influenza with the potential to cause millions of deaths. Therefore, practical influenza vaccines and vaccination strategies that can confer protection against intranasal infection with influenza viruses are needed. In this study, we demonstrate that using LTK63, a nontoxic mutant of the heat-labile toxin from Escherichia coli, as an adjuvant for both mucosal and systemic immunizations, systemic (intramuscular) immunization or combinations of mucosal (intranasal) and intramuscular immunizations protected mice against intranasal challenge with a lethal dose of live influenza virus at 3.5 months after the second immunization.

The Impact of Mass School Immunization on School Attendance

ERIC Educational Resources Information Center

Wiggs-Stayner, Kathleen S.; Purdy, Teresa R.; Go, Gailya N.; McLaughlin, Natalie C.; Tryzynka, Penny S.; Sines, Joyce R.; Hlaing, Thein

2006-01-01

The purpose of this study was to assess the impact a free, on-site influenza immunization program could have on attendance in Title 1 schools. Four Title 1 elementary schools participated in the study. Students at 2 schools were offered free FluMist[R] immunizations on site, and students at 2 control schools were not. Compliance on receiving…

Progress in Vaccine-Preventable and Respiratory Infectious Diseases-First 10 Years of the CDC National Center for Immunization and Respiratory Diseases, 2006-2015.

PubMed

Schuchat, Anne; Anderson, Larry J; Rodewald, Lance E; Cox, Nancy J; Hajjeh, Rana; Pallansch, Mark A; Messonnier, Nancy E; Jernigan, Daniel B; Wharton, Melinda

2018-07-01

The need for closer linkages between scientific and programmatic areas focused on addressing vaccine-preventable and acute respiratory infections led to establishment of the National Center for Immunization and Respiratory Diseases (NCIRD) at the Centers for Disease Control and Prevention. During its first 10 years (2006-2015), NCIRD worked with partners to improve preparedness and response to pandemic influenza and other emergent respiratory infections, provide an evidence base for addition of 7 newly recommended vaccines, and modernize vaccine distribution. Clinical tools were developed for improved conversations with parents, which helped sustain childhood immunization as a social norm. Coverage increased for vaccines to protect adolescents against pertussis, meningococcal meningitis, and human papillomavirus-associated cancers. NCIRD programs supported outbreak response for new respiratory pathogens and oversaw response of the Centers for Disease Control and Prevention to the 2009 influenza A(H1N1) pandemic. Other national public health institutes might also find closer linkages between epidemiology, laboratory, and immunization programs useful.

Influenza immunization rates in children and teenagers in Polish cities: conclusions from the 2009/2010 season.

PubMed

Kuchar, Ernest; Nitsch-Osuch, Aneta; Zycinska, Katarzyna; Miskiewicz, Katarzyna; Szenborn, Leszek; Wardyn, Kazimierz

2013-01-01

The aim of this study was to determine influenza vaccine coverage among children aged 0-18 years in inner city practices in Poland in the 2009/2010 season and factors that might have influenced low vaccination coverage. A retrospective review of 11,735 vaccination charts of children aged 0-18 from seven randomly selected general practices in the capital city of Warsaw and one large practice in the city of Wroclaw was performed. We calculated the numbers of children who were vaccinated in the 2009/2010 season and analyzed the age distribution of vaccinated children. We also reviewed the vaccination history in patients who were vaccinated against influenza including: previous influenza vaccinations, modification (widening) of standard immunization scheme, and a proportion of children who completed the recommended two-dose schedule of vaccination. In the calculations, 95% confidence intervals were used. Out of the total of 11,735 children surveyed, 362 (3.1%, CI: 2.8-3.4%) were vaccinated against influenza in the 2009/2010 season. For 115 of these 362 (31.8%, CI: 27.0-36.6%) children it was their first vaccination against influenza. The mean age of a vaccinated child was 6.0 ± 4.3 years. Children aged 2-5 were most commonly vaccinated (153/362, 42.3%, CI: 37.2-47.4%), while infants (aged 6-12 months) were vaccinated rarely (15/362, 4.4%, CI: 2.2-6.2%). In the group of children younger than 8 years (86/362 children) who were vaccinated for the first time in their life only 29/86 (33.7%, CI: 23.7-43.7%) completed the recommended two-dose schedule. In conclusion, the importance of vaccinating children against influenza is hugely understated in Poland. General physicians should actively recommend annual influenza immunization of children. Recommendations of National Immunization Program concerning influenza vaccine should be clearer, simpler, and easier to implement.

Influenza immunization among Canadian health care personnel: a cross-sectional study

PubMed Central

Buchan, Sarah A.; Kwong, Jeffrey C.

2016-01-01

Background: Influenza immunization coverage among Canadian health care personnel remains below national targets. Targeting this group is of particular importance given their elevated risk of influenza infection, role in transmission and influence on patients' immunization status. We examined influenza immunization coverage in health care personnel in Canada, reasons for not being immunized and the impact of "vaccinate-or-mask" influenza prevention policies. Methods: In this national cross-sectional study, we pooled data from the 2007 to 2014 cycles of the Canadian Community Health Survey and restricted it to respondents who reported a health care occupation. Using bootstrapped survey weights, we examined immunization coverage by occupation and by presence of vaccinate-or-mask policies, and reasons for not being immunized. We used modified Poisson regression to estimate the prevalence ratio (PR) of influenza immunization for health care occupations compared with the general working population. Results: For all survey cycles combined, 50% of 18 446 health care personnel reported receiving seasonal influenza immunization during the previous 12 months, although this varied by occupation type (range 4%-72%). Compared with the general working population, family physicians and general practitioners were most likely to be immunized (PR 3.15, 95% confidence interval [CI] 2.76-3.59), whereas chiropractors, midwives and practitioners of natural healing were least likely (PR 0.17, 95% CI 0.10-0.30). Among those who were not immunized, the most frequently cited reason was the belief that influenza immunization is unnecessary. Introduction of vaccinate-or-mask policies was associated with increased influenza immunization among health care personnel. Interpretation: Health care personnel are more likely to be immunized against influenza than the general working population, but coverage remains suboptimal overall, and we observed wide variation by occupation type. More efforts are needed to target specific health care occupations with low immunization coverage. PMID:27730112

Stabilization of Influenza Vaccine Enhances Protection by Microneedle Delivery in the Mouse Skin

PubMed Central

Yoo, Dae-Goon; Compans, Richard W.; Prausnitz, Mark R.; Kang, Sang-Moo

2009-01-01

Background Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy. Methodology/Principal Findings Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge. Conclusions/Significance The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too. PMID:19779615

Pattern recognition receptor immunomodulation of innate immunity as a strategy to limit the impact of influenza virus.

PubMed

Pizzolla, Angela; Smith, Jeffery M; Brooks, Andrew G; Reading, Patrick C

2017-04-01

Influenza remains a major global health issue and the effectiveness of current vaccines and antiviral drugs is limited by the continual evolution of influenza viruses. Therefore, identifying novel prophylactic or therapeutic treatments that induce appropriate innate immune responses to protect against influenza infection would represent an important advance in efforts to limit the impact of influenza. Cellular pattern recognition receptors (PRRs) recognize conserved structures expressed by pathogens to trigger intracellular signaling cascades, promoting expression of proinflammatory molecules and innate immunity. Therefore, a number of approaches have been developed to target specific PRRs in an effort to stimulate innate immunity and reduce disease in a variety of settings, including during influenza infections. Herein, we discuss progress in immunomodulation strategies designed to target cell-associated PRRs of the innate immune system, thereby, modifying innate responses to IAV infection and/or augmenting immune responses to influenza vaccines. © Society for Leukocyte Biology.

Knowledge, awareness and practices towards seasonal influenza and its vaccine: implications for future vaccination campaigns in Jordan.

PubMed

Abu-Rish, Eman Y; Elayeh, Eman R; Mousa, Lubabah A; Butanji, Yasser K; Albsoul-Younes, Abla M

2016-12-01

Influenza is an underestimated contributor to morbidity and mortality. Population knowledge regarding influenza and its vaccination has a key role in enhancing vaccination coverage. This study aimed to identify the gaps of knowledge among Jordanian population towards influenza and its vaccine, and to identify the major determinants of accepting seasonal influenza vaccine in adults and children in Jordan. This was a cross-sectional study that enrolled 941 randomly selected adults in Amman, Jordan. A four-section questionnaire was used which included questions about the sociodemographic characteristics, knowledge about influenza and the factors that affect seasonal influenza vaccine acceptance and refusal. Only 47.3% of the participants were considered knowledgeable. About half of the participants (51.9%) correctly identified the main influenza preventative measures. Lack of knowledge about the important role of seasonal influenza vaccine in disease prevention was observed. Low vaccination rate (20% of adults) was reported. The most critical barrier against vaccination in adults and children was the concern about the safety and the efficacy of the vaccine, while the most important predictors for future vaccination in adults and children were physician recommendation and government role. In children, the inclusion of the vaccine within the national immunization program was an important determinant of vaccine acceptance. Formulating new strategies to improve the population's level of knowledge, assuring the population about the safety and the efficacy of the vaccine and the inclusion of the vaccine within the national immunization program are the essential factors to enhance vaccination coverage in Jordan. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Protective Role of γδ T Cells in Cigarette Smoke and Influenza Infection

PubMed Central

Hong, M. J.; Gu, B. H.; Madison, M.; Landers, C.; Tung, H. Y.; Kim, M.; Yuan, X.; You, R.; MacHado, A. A.; Gilbert, B. E.; Soroosh, P.; Elloso, M.; Song, L.; Chen, M.; Corry, D. B.; Diehl, G.; Kheradmand, F.

2017-01-01

Airborne pathogens commonly trigger severe respiratory failure or death in smokers with lung disease. Cigarette smoking compromises the effectiveness of innate immunity against infections but the underlying mechanisms responsible for defective acquired immune responses in smokers remains less clear. We found that mice exposed to chronic cigarette smoke recovered poorly from primary Influenza A pneumonia with reduced type I and II interferons (IFNs) and viral-specific immunoglobulins, but recruited gamma delta (γδ) T cells to the lungs that predominantly expressed interleukin 17A (IL-17A). Il-17a-/- mice exposed to smoke and infected with Influenza A also recruited γδ T cells to the lungs, but in contrast to wild type mice, expressed increased IFNs, made protective influenza specific antibodies, and recovered from infection. Depletion of IL-17A with blocking antibodies significantly increased T-bet expression in γδ T cells and improved recovery from acute Influenza A infection in air, but not smoke exposed mice. In contrast, when exposed to smoke, γδ T cell deficient mice failed to mount an effective immune response to Influenza A and showed increased mortality. Our findings demonstrate a protective role for γδ T cells in smokers and suggest that smoke-induced increase in IL-17A inhibits the transcriptional programs required for their optimal anti-viral responses. PMID:29091081

A randomized trial of maternal influenza immunization decision-making: A test of persuasive messaging models.

PubMed

Frew, Paula M; Kriss, Jennifer L; Chamberlain, Allison T; Malik, Fauzia; Chung, Yunmi; Cortés, Marielysse; Omer, Saad B

2016-08-02

We sought to examine the effectiveness of persuasive communication interventions on influenza vaccination uptake among black/African American pregnant women in Atlanta, Georgia. We recruited black/African American pregnant women ages 18 to 50 y from Atlanta, GA to participate in a prospective, randomized controlled trial of influenza immunization messaging conducted from January to April 2013. Eligible participants were randomized to 3 study arms. We conducted follow-up questionnaires on influenza immunization at 30-days post-partum with all groups. Chi-square and t tests evaluated group differences, and outcome intention-to-treat assessment utilized log-binomial regression models. Of the 106 enrolled, 95 women completed the study (90% retention), of which 31 were randomly assigned to affective messaging intervention ("Pregnant Pause" video), 30 to cognitive messaging intervention ("Vaccines for a Healthy Pregnancy" video), and 34 to a comparison condition (receipt of the Influenza Vaccine Information Statement). The three groups were balanced on baseline demographic characteristics and reported health behaviors. At baseline, most women (63%, n = 60) reported no receipt of seasonal influenza immunization during the previous 5 y. They expressed a low likelihood (2.1 ± 2.8 on 0-10 scale) of obtaining influenza immunization during their current pregnancy. At 30-days postpartum follow-up, influenza immunization was low among all participants (7-13%) demonstrating no effect after a single exposure to either affective messaging (RR = 1.10; 95% CI: 0.30-4.01) or cognitive messaging interventions (RR = 0.57; 95% CI: 0.11-2.88). Women cited various reasons for not obtaining maternal influenza immunizations. These included concern about vaccine harm (47%, n = 40), low perceived influenza infection risk (31%, n = 26), and a history of immunization nonreceipt (24%, n = 20). The findings reflect the limitations associated with a single exposure to varying maternal influenza immunization message approaches on vaccine behavior. For this population, repeated influenza immunization exposures may be warranted with alterations in message format, content, and relevance for coverage improvement.

Increasing influenza vaccination coverage in recommended population groups in Europe.

PubMed

Blank, Patricia R; Szucs, Thomas D

2009-04-01

The clinical and economic burden of seasonal influenza is frequently underestimated. The cornerstone of controlling and preventing influenza is vaccination. National and international guidelines aim to implement immunization programs and targeted vaccination-coverage rates, which should help to enhance the vaccine uptake, especially in the at-risk population. This review purposes to highlight the vaccination guidelines and the actual vaccination situation in four target groups (the elderly, people with underlying chronic conditions, healthcare workers and children) from a European point of view.

Antibody immunoprophylaxis and immunotherapy for influenza virus infection: Utilization of monoclonal or polyclonal antibodies?

PubMed

Berry, Cassandra M

2018-03-04

Control programs for emerging influenza are in urgent need of novel therapeutic strategies to mitigate potentially devastating threats from pathogenic strains with pandemic potential. Current vaccines and antivirals have inherent limitations in efficacy, especially with rapid evolutionary changes of influenza viruses. Antibody-based antiviral protection harnesses the natural power of the immune system. Antibodies present prophylactic and therapeutic intervention options for prevention and control of influenza, especially for at-risk populations. Specific monoclonal antibodies are well defined in purity and initial efficacy but polyclonal antibodies are easier to scale-up and cost-effective with long-term efficacy, using batches with broadly neutralizing properties against influenza variants. This review presents the pros and cons of monoclonal versus polyclonal antibody therapy for influenza.

Immunogenetics of Seasonal Influenza Vaccine Response*

PubMed Central

Poland, Gregory A.; Ovsyannikova, Inna G.; Jacobson, Robert M.

2008-01-01

Seasonal influenza causes significant morbidity, mortality, and economic costs. Vaccines against influenza, though both safe and effective, are imperfect. Notably, these vaccines result in significant immune response variability across the population. The mechanism for this variability, in part, appears to lie in the polymorphisms of key immune response genes. Despite the importance of this variability, little in the way of genetic polymorphisms and its association with vaccine immune response to viral vaccines has been performed. Herein, we review and synthesize what is known about the immune response pathway and influenza viral immunity and then present original data from our laboratory on the immunogenetic relationships between HLA, cytokine and cytokine receptor gene polymorphisms and the variations in humoral immune response to inactivated seasonal influenza vaccine. Finally, we propose that a better understanding of vaccine immunogenetics offers insight towards the development of better influenza vaccines. PMID:19230157

Innate Immune Sensing and Response to Influenza

PubMed Central

Pulendran, Bali; Maddur, Mohan S.

2015-01-01

Influenza viruses pose a substantial threat to human and animal health worldwide. Recent studies in mouse models have revealed an indispensable role for the innate immune system in defense against influenza virus. Recognition of the virus by innate immune receptors in a multitude of cell types activates intricate signaling networks, functioning to restrict viral replication. Downstream effector mechanisms include activation of innate immune cells and, induction and regulation of adaptive immunity. However, uncontrolled innate responses are associated with exaggerated disease, especially in pandemic influenza virus infection. Despite advances in the understanding of innate response to influenza in the mouse model, there is a large knowledge gap in humans, particularly in immunocom-promised groups such as infants and the elderly. We propose here, the need for further studies in humans to decipher the role of innate immunity to influenza virus, particularly at the site of infection. These studies will complement the existing work in mice and facilitate the quest to design improved vaccines and therapeutic strategies against influenza. PMID:25078919

Innate immune sensing and response to influenza.

PubMed

Pulendran, Bali; Maddur, Mohan S

2015-01-01

Influenza viruses pose a substantial threat to human and animal health worldwide. Recent studies in mouse models have revealed an indispensable role for the innate immune system in defense against influenza virus. Recognition of the virus by innate immune receptors in a multitude of cell types activates intricate signaling networks, functioning to restrict viral replication. Downstream effector mechanisms include activation of innate immune cells and, induction and regulation of adaptive immunity. However, uncontrolled innate responses are associated with exaggerated disease, especially in pandemic influenza virus infection. Despite advances in the understanding of innate response to influenza in the mouse model, there is a large knowledge gap in humans, particularly in immunocompromised groups such as infants and the elderly. We propose here, the need for further studies in humans to decipher the role of innate immunity to influenza virus, particularly at the site of infection. These studies will complement the existing work in mice and facilitate the quest to design improved vaccines and therapeutic strategies against influenza.

The Vote and Vax program: public health at polling places.

PubMed

Shenson, Douglas; Adams, Mary

2008-01-01

Although influenza-associated illness is a major cause of hospitalizations and death among older Americans, only half of adults aged 50 or older-for whom influenza vaccinations are recommended-receive an annual influenza vaccination. National elections, which draw a large number of older voters, take place during influenza vaccination season and represent an untapped opportunity for large-scale delivery of vaccinations. In 2006, the Robert Wood Johnson Foundation launched a program to evaluate the feasibility of delivering influenza vaccinations near polling places. Twenty-five public health agencies were each provided grants of $8000 and asked to implement at least two Vote and Vax clinics. Immunizers were required to obtain prior permission from local election authorities and to charge fees as they would at their other community-based clinics. Influenza vaccination had to be made available both to voters and to nonvoters. On election day, the initiative delivered 13790 influenza vaccinations at 127 polling places in 14 states. More than 80 percent of adult vaccine recipients were in the Centers for Disease Prevention and Control-defined priority groups and 28 percent were "new" influenza vaccination recipients. Vote and Vax is a potentially national strategy that could significantly expand the delivery of influenza vaccinations.

Sequencing, annotation, and characterization of the influenza ferret infectome.

PubMed

León, Alberto J; Banner, David; Xu, Luoling; Ran, Longsi; Peng, Zhiyu; Yi, Kang; Chen, Chao; Xu, Fengping; Huang, Jinrong; Zhao, Zhen; Lin, Zhen; Huang, Stephen H S; Fang, Yuan; Kelvin, Alyson A; Ross, Ted M; Farooqui, Amber; Kelvin, David J

2013-02-01

Ferrets have become an indispensable tool in the understanding of influenza virus virulence and pathogenesis. Furthermore, ferrets are the preferred preclinical model for influenza vaccine and therapeutic testing. Here we characterized the influenza infectome during the different stages of the infectious process in ferrets with and without prior specific immunity to influenza. RNA from lung tissue and lymph nodes from infected and naïve animals was subjected to next-generation sequencing, followed by de novo data assembly and annotation of the resulting sequences; this process generated a library comprising 13,202 ferret mRNAs. Gene expression profiles during pandemic H1N1 (pdmH1N1) influenza virus infection were analyzed by digital gene expression and solid support microarrays. As expected during primary infection, innate immune responses were triggered in the lung tissue; meanwhile, in the lymphoid tissue, genes encoding antigen presentation and maturation of effector cells of adaptive immunity increased dramatically. After 5 days postinfection, the innate immune gene expression was replaced by the adaptive immune response, which correlates with viral clearance. Reinfection with homologous pandemic influenza virus resulted in a diminished innate immune response, early adaptive immune gene regulation, and a reduction in clinical severity. The fully annotated ferret infectome will be a critical aid to the understanding of the molecular events that regulate disease severity and host-influenza virus interactions among seasonal, pandemic, and highly pathogenic avian influenzas.

A randomized trial of maternal influenza immunization decision-making: A test of persuasive messaging models

PubMed Central

Frew, Paula M.; Kriss, Jennifer L.; Chamberlain, Allison T.; Malik, Fauzia; Chung, Yunmi; Cortés, Marielysse; Omer, Saad B.

2016-01-01

ABSTRACT Objective: We sought to examine the effectiveness of persuasive communication interventions on influenza vaccination uptake among black/African American pregnant women in Atlanta, Georgia. Methods: We recruited black/African American pregnant women ages 18 to 50 y from Atlanta, GA to participate in a prospective, randomized controlled trial of influenza immunization messaging conducted from January to April 2013. Eligible participants were randomized to 3 study arms. We conducted follow-up questionnaires on influenza immunization at 30-days post-partum with all groups. Chi-square and t tests evaluated group differences, and outcome intention-to-treat assessment utilized log-binomial regression models. Results: Of the 106 enrolled, 95 women completed the study (90% retention), of which 31 were randomly assigned to affective messaging intervention (“Pregnant Pause” video), 30 to cognitive messaging intervention (“Vaccines for a Healthy Pregnancy” video), and 34 to a comparison condition (receipt of the Influenza Vaccine Information Statement). The three groups were balanced on baseline demographic characteristics and reported health behaviors. At baseline, most women (63%, n = 60) reported no receipt of seasonal influenza immunization during the previous 5 y. They expressed a low likelihood (2.1 ± 2.8 on 0-10 scale) of obtaining influenza immunization during their current pregnancy. At 30-days postpartum follow-up, influenza immunization was low among all participants (7-13%) demonstrating no effect after a single exposure to either affective messaging (RR = 1.10; 95% CI: 0.30-4.01) or cognitive messaging interventions (RR = 0.57; 95% CI: 0.11-2.88). Women cited various reasons for not obtaining maternal influenza immunizations. These included concern about vaccine harm (47%, n = 40), low perceived influenza infection risk (31%, n = 26), and a history of immunization nonreceipt (24%, n = 20). Conclusion: The findings reflect the limitations associated with a single exposure to varying maternal influenza immunization message approaches on vaccine behavior. For this population, repeated influenza immunization exposures may be warranted with alterations in message format, content, and relevance for coverage improvement. PMID:27322154

Generation and protective efficacy of a cold-adapted attenuated avian H9N2 influenza vaccine.

PubMed

Wei, Yandi; Qi, Lu; Gao, Huijie; Sun, Honglei; Pu, Juan; Sun, Yipeng; Liu, Jinhua

2016-07-26

To prevent H9N2 avian influenza virus infection in chickens, a long-term vaccination program using inactivated vaccines has been implemented in China. However, the protective efficacy of inactivated vaccines against antigenic drift variants is limited, and H9N2 influenza virus continues to circulate in vaccinated chicken flocks in China. Therefore, developing a cross-reactive vaccine to control the impact of H9N2 influenza in the poultry industry remains a high priority. In the present study, we developed a live cold-adapted H9N2 influenza vaccine candidate (SD/01/10-ca) by serial passages in embryonated eggs at successively lower temperatures. A total of 13 amino acid mutations occurred during the cold-adaptation of this H9N2 virus. The candidate was safe in chickens and induced robust hemagglutination-inhibition antibody responses and influenza virus-specific CD4(+) and CD8(+) T cell immune responses in chickens immunized intranasally. Importantly, the candidate could confer protection of chickens from homologous and heterogenous H9N2 viruses. These results demonstrated that the cold-adapted attenuated H9N2 virus would be selected as a vaccine to control the infection of prevalent H9N2 influenza viruses in chickens.

Generation and protective efficacy of a cold-adapted attenuated avian H9N2 influenza vaccine

PubMed Central

Wei, Yandi; Qi, Lu; Gao, Huijie; Sun, Honglei; Pu, Juan; Sun, Yipeng; Liu, Jinhua

2016-01-01

To prevent H9N2 avian influenza virus infection in chickens, a long-term vaccination program using inactivated vaccines has been implemented in China. However, the protective efficacy of inactivated vaccines against antigenic drift variants is limited, and H9N2 influenza virus continues to circulate in vaccinated chicken flocks in China. Therefore, developing a cross-reactive vaccine to control the impact of H9N2 influenza in the poultry industry remains a high priority. In the present study, we developed a live cold-adapted H9N2 influenza vaccine candidate (SD/01/10-ca) by serial passages in embryonated eggs at successively lower temperatures. A total of 13 amino acid mutations occurred during the cold-adaptation of this H9N2 virus. The candidate was safe in chickens and induced robust hemagglutination-inhibition antibody responses and influenza virus–specific CD4+ and CD8+ T cell immune responses in chickens immunized intranasally. Importantly, the candidate could confer protection of chickens from homologous and heterogenous H9N2 viruses. These results demonstrated that the cold-adapted attenuated H9N2 virus would be selected as a vaccine to control the infection of prevalent H9N2 influenza viruses in chickens. PMID:27457755

Seasonal and 2009 H1N1 influenza vaccine uptake, predictors of vaccination and self-reported barriers to vaccination among secondary school teachers and staff

PubMed Central

Painter, Julia E; Sales, Jessica M; Morfaw, Christopher; Jones, LaDawna M; Murray, Dennis; Wingood, Gina M; DiClemente, Ralph J; Hughes, James M

2011-01-01

Objective Teachers, like healthcare workers, may be a strategic target for influenza immunization programs. Influenza vaccination is critical to protect both teachers and the students they come into contact with. This study assessed factors associated with seasonal and H1N1 influenza vaccine uptake among middle- and high-school teachers. Results Seventy-eight percent of teachers who planned to receive seasonal influenza vaccine and 36% of those who planned to receive H1N1 influenza vaccine at baseline reported that they did so. Seasonal vaccine uptake was significantly associated with perceived severity (odds ratio [OR] 1.57, p = 0.05) and self-efficacy (OR 4.46, p = 0.006). H1N1 vaccine uptake was associated with perceived barriers (OR 0.7, p = 0.014) and social norms (OR 1.39, p = 0.05). The number one reason for both seasonal and H1N1 influenza vaccine uptake was to avoid getting seasonal/H1N1 influenza disease. The number one reason for seasonal influenza vaccine refusal was a concern it would make them sick and for H1N1 influenza vaccine refusal was concern about vaccine side effects. Methods Participants were recruited from two counties in rural Georgia. Data were collected from surveys in September 2009 and May 2010. Multivariate logistic regression was used to assess the association between teachers' attitudes toward seasonal and H1N1 influenza vaccination and vaccine uptake. Conclusions There is a strong association between the intention to be vaccinated against influenza (seasonal or 2009 H1N1) and actual vaccination uptake. Understanding and addressing factors associated with teachers' influenza vaccine uptake may enhance future influenza immunization efforts. PMID:21263225

Measuring Cellular Immunity to Influenza: Methods of Detection, Applications and Challenges

PubMed Central

Coughlan, Lynda; Lambe, Teresa

2015-01-01

Influenza A virus is a respiratory pathogen which causes both seasonal epidemics and occasional pandemics; infection continues to be a significant cause of mortality worldwide. Current influenza vaccines principally stimulate humoral immune responses that are largely directed towards the variant surface antigens of influenza. Vaccination can result in an effective, albeit strain-specific antibody response and there is a need for vaccines that can provide superior, long-lasting immunity to influenza. Vaccination approaches targeting conserved viral antigens have the potential to provide broadly cross-reactive, heterosubtypic immunity to diverse influenza viruses. However, the field lacks consensus on the correlates of protection for cellular immunity in reducing severe influenza infection, transmission or disease outcome. Furthermore, unlike serological methods such as the standardized haemagglutination inhibition assay, there remains a large degree of variation in both the types of assays and method of reporting cellular outputs. T-cell directed immunity has long been known to play a role in ameliorating the severity and/or duration of influenza infection, but the precise phenotype, magnitude and longevity of the requisite protective response is unclear. In order to progress the development of universal influenza vaccines, it is critical to standardize assays across sites to facilitate direct comparisons between clinical trials. PMID:26343189

Impact of introduction of the Haemophilus influenzae type b conjugate vaccine into childhood immunization on meningitis in Bangladeshi infants.

PubMed

Sultana, Nadira K; Saha, Samir K; Al-Emran, Hassan M; Modak, Joyanta K; Sharker, M A Yushuf; El-Arifeen, Shams; Cohen, Adam L; Baqui, Abdullah H; Luby, Stephen P

2013-07-01

Some Asian countries have been reluctant to adopt Haemophilus influenzae type b (Hib) conjugate vaccination because of uncertainty over disease burden. We assessed the impact of introduction of Hib conjugate vaccine into the Expanded Program on Immunization in Bangladesh on purulent and laboratory-confirmed H influenzae meningitis. Within a well-defined catchment area around 2 surveillance hospitals in Dhaka, Bangladesh, we compared the incidence of Hib meningitis confirmed by culture, latex agglutination, and polymerase chain reaction assay among infants 1 year before and 1 year after introduction of Hib conjugate vaccine. We adjusted the incidence rate for the proportion of children who sought care at the surveillance hospitals. Among infants, the incidence of confirmed Hib meningitis decreased from 92-16 cases per 100,000 within 1 year of vaccine introduction (vaccine preventable incidence = 76; 95% CI 18, 135 per 100,000). The incidence of purulent meningitis decreased from 1659-1159 per 100,000 (vaccine preventable incidence = 500; 95% CI: 203, 799 per 100,000). During the same time period, there was no significant difference in the incidence of meningitis due to Streptococcus pneumoniae. Introduction of conjugate Hib conjugate vaccine into Bangladesh Expanded Program on Immunization markedly reduced the burden of Hib and purulent meningitis. Copyright © 2013. Published by Mosby, Inc.

The Split Virus Influenza Vaccine rapidly activates immune cells through Fcγ receptors.

PubMed

O'Gorman, William E; Huang, Huang; Wei, Yu-Ling; Davis, Kara L; Leipold, Michael D; Bendall, Sean C; Kidd, Brian A; Dekker, Cornelia L; Maecker, Holden T; Chien, Yueh-Hsiu; Davis, Mark M

2014-10-14

Seasonal influenza vaccination is one of the most common medical procedures and yet the extent to which it activates the immune system beyond inducing antibody production is not well understood. In the United States, the most prevalent formulations of the vaccine consist of degraded or "split" viral particles distributed without any adjuvants. Based on previous reports we sought to determine whether the split influenza vaccine activates innate immune receptors-specifically Toll-like receptors. High-dimensional proteomic profiling of human whole-blood using Cytometry by Time-of-Flight (CyTOF) was used to compare signaling pathway activation and cytokine production between the split influenza vaccine and a prototypical TLR response ex vivo. This analysis revealed that the split vaccine rapidly and potently activates multiple immune cell types but yields a proteomic signature quite distinct from TLR activation. Importantly, vaccine induced activity was dependent upon the presence of human sera indicating that a serum factor was necessary for vaccine-dependent immune activation. We found this serum factor to be human antibodies specific for influenza proteins and therefore immediate immune activation by the split vaccine is immune-complex dependent. These studies demonstrate that influenza virus "splitting" inactivates any potential adjuvants endogenous to influenza, such as RNA, but in previously exposed individuals can elicit a potent immune response by facilitating the rapid formation of immune complexes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Changes in Influenza Vaccination Rates After Withdrawal of Live Vaccine.

PubMed

Robison, Steve G; Dunn, Aaron G; Richards, Deborah L; Leman, Richard F

2017-11-01

Before the start of the 2016-2017 influenza season, the Advisory Committee on Immunization Practices withdrew its recommendation promoting the use of live attenuated influenza vaccines (LAIVs). There was concern that this might lessen the likelihood that those with a previous LAIV would return for an injectable influenza vaccine (IIV) and that child influenza immunization rates would decrease overall. Using Oregon's statewide immunization registry, the ALERT Immunization Information System, child influenza immunization rates were compared across the 2012-2013 through 2016-2017 seasons. Additionally, matched cohorts of children were selected based on receipt of either an LAIV or an IIV during the 2015-2016 season. Differences between the IIV and LAIV cohorts in returning for the IIV in the 2016-2017 season were assessed. Overall, influenza immunization rates for children aged 2 to 17 years were unchanged between the 2015-2016 and 2016-2017 seasons. Children aged 3 to 10 with a previous IIV were 1.03 (95% confidence interval, 1.02 to 1.04) times more likely to return for an IIV in 2016-2017 than those with a previous LAIV, whereas children aged 11 to 17 years with a previous IIV were 1.08 (95% confidence interval, 1.05 to -1.09) times more likely to return. Withdrawal of the LAIV recommendation was not associated with an overall change in child influenza immunization rates across seasons. Children with a previous (2015-2016) IIV were slightly more likely to return during the 2016-2017 season for influenza immunization than those with a previous LAIV. Copyright © 2017 by the American Academy of Pediatrics.

Antibody responses to avian influenza viruses in wild birds broaden with age

PubMed Central

Manvell, Ruth J.; Schulenburg, Bodo; Shell, Wendy; Wikramaratna, Paul S.; Perrins, Christopher; Sheldon, Ben C.; Brown, Ian H.; Pybus, Oliver G.

2016-01-01

For viruses such as avian influenza, immunity within a host population can drive the emergence of new strains by selecting for viruses with novel antigens that avoid immune recognition. The accumulation of acquired immunity with age is hypothesized to affect how influenza viruses emerge and spread in species of different lifespans. Despite its importance for understanding the behaviour of avian influenza viruses, little is known about age-related accumulation of immunity in the virus's primary reservoir, wild birds. To address this, we studied the age structure of immune responses to avian influenza virus in a wild swan population (Cygnus olor), before and after the population experienced an outbreak of highly pathogenic H5N1 avian influenza in 2008. We performed haemagglutination inhibition assays on sampled sera for five avian influenza strains and show that breadth of response accumulates with age. The observed age-related distribution of antibody responses to avian influenza strains may explain the age-dependent mortality observed during the highly pathogenic H5N1 outbreak. Age structures and species lifespan are probably important determinants of viral epidemiology and virulence in birds. PMID:28003449

School-located influenza vaccination and absenteeism among elementary school students in a Hispanic community.

PubMed

Keck, Patricia C; Ynalvez, Marcus Antonius; Gonzalez, Hector F; Castillo, Keila D

2013-08-01

Seasonal influenza is recognized as a significant health burden to children and is a cause of excess school absenteeism in children. In 2008, the Advisory Committee on Immunization Practices recommended annual influenza vaccination for all children 6 months to 18 years of age. School nurses influence participation in this recommendation by conducting school-located influenza vaccination (SLIV) programs at their campuses. Knowing the effect of SLIV programs on student absenteeism may motivate school nurses and district administrators to conduct such vaccination programs. This study examines the impact of an SLIV program on elementary school absenteeism in an inner city school district with a predominantly Hispanic population. Using Poisson regression models with robust standard errors, we analyzed data from 3,775 records obtained by stratified random sampling. Results of the study indicate that students vaccinated through an SLIV program have fewer absences than unvaccinated students. A surprising result of the study shows that students vaccinated through an SLIV program had fewer absences than students vaccinated elsewhere. These results are of particular importance to school nurses who work with large Hispanic populations. Our study illustrates one way that a school nurse can assess the effect of an SLIV program on absenteeism.

[Haemophilus influenzae b among bacterial meningitis in Bamako (2002-2004)].

PubMed

Diawara, A; Sangho, H; Sissoko, M; Bougoudogo, F; Doumbo, O

2008-01-01

In Mali little study exist on the meningitis with Haemophilus influenzae b (Hib). This weak data availability on Hib meningitis, didn't permit to introduce the immunization against this pathology in the Expanded Program Immunization (EPI) of Mali. The present survey aims to improve the availability of the data on Hib meningitis and to advocate for the introduction of immunization against Hib in EPI in Mali. The survey consisted to the exploitation of spinal fluid examination data for the suspected cases of meningitis, sent by the different health centers to National Institute for Public Health Research (INRSP) on the period going from October 1st, 2002 to September 30, 2004. According to the survey, on 230 cases of meningitis whose germs have been identified to the latex and the culture, Hib occupies the 3rd place with 21.3% among the bacterial meningitises. In Bamako Hib occupies the 2nd place (27.4%) according to the source. The persons less than 1 year (59.6%) were the more affected (p < 0.001) and the diseases distribution has been observed during the dry seasons (51.0%) and rainy (49.0%) without meaningful impact of temperature and rainfall (p > 0.05) (p = 0.8249). The cases of Hib identified were more sensitive to ciprofloxacine (100%) and to ceftriaxone (100%). Taken into consideration the cost raised of quinolones and cephalosporines, and in reference to the high mortality and frequent complications known of Hib meningitis, the introduction of immunization against Haemophilus influenzae in the Expanded Program Immunization should contribute to a better control of this disease.

Factors associated with maternal influenza immunization decision-making. Evidence of immunization history and message framing effects.

PubMed

Frew, Paula M; Owens, Lauren E; Saint-Victor, Diane S; Benedict, Samantha; Zhang, Siyu; Omer, Saad B

2014-01-01

We examined pregnant women's intention to obtain the seasonal influenza vaccine via a randomized controlled study examining the effects of immunization history, message exposure, and sociodemographic correlates. Pregnant women ages 18-50 participated in a randomized message framing study from September 2011 through May 2012. Venue-based sampling was used to recruit racial and ethnic minority women throughout Atlanta, Georgia. Key outcomes were evaluated using bivariate and multivariate analyses. History of influenza immunization was positively associated with intent to immunize during pregnancy [OR=2.31, 90%CI: (1.06, 5.00)]. Significant correlates of intention to immunize included perceived susceptibility to influenza during pregnancy [OR=3.8, 90% CI: (1.75, 8.36)] and vaccine efficacy [OR=10.53, 90% CI: (4.34, 25.50)]. Single message exposure did not influence a woman's intent to vaccinate. Prior immunization, perceived flu susceptibility and perceived vaccine effectiveness promoted immunization intent among this population of pregnant minority women. Vaccine efficacy and disease susceptibility are critical to promoting immunization among women with no history of seasonal influenza immunization, while those who received the vaccine are likely to do so again. These findings provide evidence for the promotion of repeated exposure to vaccine messages emphasizing vaccine efficacy, normative support, and susceptibility to influenza.

THE EFFECT OF HEMOPHILUS INFLUENZAE SUIS VACCINES ON SWINE INFLUENZA

PubMed Central

Shope, Richard E.

1937-01-01

Either living or heat-killed H. influenzae suis vaccines, given intramuscularly to swine, elicit an immune response capable of modifying the course of a later swine influenza infection. The protection afforded is only partial and is in no way comparable to the complete immunity afforded by swine influenza virus vaccines. PMID:19870654

The 2009-2010 influenza pandemic: effects on pandemic and seasonal vaccine uptake and lessons learned for seasonal vaccination campaigns.

PubMed

Poland, Gregory A

2010-09-07

Individual and national/cultural differences were apparent in response to the 2009-2010 influenza pandemic. Overall pandemic influenza immunization rates were low across all nations, including among healthcare workers. Among the reasons for the low coverage rates may have been a lack of concern about the individual risk of influenza, which may translate into a lack of willingness or urgency to be vaccinated, particularly if there is mistrust of information provided by public health or governmental authorities. Intuitively, a link between willingness to be vaccinated against seasonal influenza and against pandemic influenza exists, given the similarities in decision-making for this infection. As such, the public is likely to share common concerns regarding pandemic and seasonal influenza vaccination, particularly in the areas of vaccine safety and side effects, and personal risk. Given the public's perception of the low level of virulence of the recent pandemic influenza virus, there is concern that the perception of a lack of personal risk of infection and risk of vaccine side effects could adversely affect seasonal vaccine uptake. While governments are more often concerned about public anxiety and panic, as well as absenteeism of healthcare and other essential workers during a pandemic, convincing the public of the threat posed by pandemic or seasonal influenza is often the more difficult, and underappreciated task. Thus, appropriate, timely, and data-driven health information are very important issues in increasing influenza vaccine coverage, perhaps even more so in western societies where trust in government and public health reports may be lower than in other countries. This article explores what has been learned about cross-cultural responses to pandemic influenza, and seeks to apply those lessons to seasonal influenza immunization programs. 2010 Elsevier Ltd. All rights reserved.

Contribution of Vaccine-Induced Immunity toward either the HA or the NA Component of Influenza Viruses Limits Secondary Bacterial Complications▿

PubMed Central

Huber, Victor C.; Peltola, Ville; Iverson, Amy R.; McCullers, Jonathan A.

2010-01-01

Secondary bacterial infections contribute to morbidity and mortality from influenza. Vaccine effectiveness is typically assessed using prevention of influenza, not secondary infections, as an endpoint. We vaccinated mice with formalin-inactivated influenza virus vaccine preparations containing disparate HA and NA proteins and demonstrated an ability to induce the appropriate anti-HA and anti-NA immune profiles. Protection from both primary viral and secondary bacterial infection was demonstrated with vaccine-induced immunity directed toward either the HA or the NA. This finding suggests that immunity toward the NA component of the virion is desirable and should be considered in generation of influenza vaccines. PMID:20130054

The Concordance of Parent and Child Immunization.

PubMed

Robison, Steve G; Osborn, Andrew W

2017-05-01

A substantial body of work has related survey-based parental vaccine hesitancy to noncompliant childhood immunization. However little attention has been paid to the connection between parents' own immunization behavior and the immunizations their children receive. Using the Oregon ALERT Immunization Information System, we identified adult caregiver-child pairs for children between 9 months and 17 years of age. The likelihood of adult-child concordance of influenza immunization per influenza season from 2010-2011 through 2014-2015 was assessed. The utility of adult immunization as a predictor was also assessed for other, noninfluenza recommended immunizations for children and adolescents. A total of 450 687 matched adult caregiver-child pairs were included in the study. The children of immunizing adults were 2.77 times more likely to also be immunized for seasonal influenza across all seasons (95% confidence interval, 2.74-2.79), with similar results applying within each season. Adult immunization status was also significantly associated with the likelihood of children and adolescents getting other noninfluenza immunizations, such as the human papillomavirus vaccine (HPV). When adults improved their own behavior from nonimmunizing to immunizing across influenza seasons, their children if not immunized in the previous season were 5.44 times (95% confidence interval, 5.35-5.53) more likely to become immunized for influenza. Children's likelihood of following immunization recommendations is associated with the immunization behavior of their parents. Encouraging parental immunization is a potential tool for increasing children's immunization rates. Copyright © 2017 by the American Academy of Pediatrics.

[Immune system and influenza virus].

PubMed

Wierzbicka-Woś, Anna; Tokarz-Deptuła, Beata; Deptuła, Wiesław

2015-02-15

Influenza viruses are a significant cause of respiratory infections, causing 3-5 million clinical infections and 250-500 thousand deaths per year. Infections caused by the influenza virus induce a host immune response at the non-specific and specific level (defined as natural and acquired), which leads to limitation of virus replication. Moreover the elements of immunological memory are induced so that they can protect against subsequent infection by the influenza virus. However, there is still no effective way for the total elimination of this virus, and the only effective method to combat this pathogen appears to be vaccination, which through immune system activation greatly limits its spread. The present paper presents the immune reaction at different levels in response to the influenza virus after entering the body and the mechanisms of the influenza virus for avoiding reactions of the immune system, which correspond to its high variability at the molecular level. Moreover, in this paper we describe various methods of stimulating the organism's immune systems with different generations of vaccines and their effectiveness in the fight against this pathogen.

Vaccine approaches conferring cross-protection against influenza viruses

PubMed Central

Vemula, Sai V.; Sayedahmed, Ekramy E; Sambhara, Suryaprakash; Mittal, Suresh K.

2018-01-01

Introduction Annual vaccination is one of the most efficient and cost-effective strategies to prevent and control influenza epidemics. Most of currently available influenza vaccines are strong inducer of antibody responses against viral surface proteins, hemagglutinin (HA) and neuraminidase (NA), but are poor inducers of cell-mediated immune responses against conserved internal proteins. Moreover, due to the high variability of viral surface proteins because of antigenic drift or antigenic shift, many of the currently licensed vaccines confer little or no protection against drift or shift variants. Areas covered Next generation influenza vaccines that can induce humoral immune responses to receptor-binding epitopes as well as broadly neutralizing conserved epitopes, and cell-mediated immune responses against highly conserved internal proteins would be effective against variant viruses as well as a novel pandemic influenza until circulating strain-specific vaccines become available. Here we discuss vaccine approaches that have potential to provide broad spectrum protection against influenza viruses. Expert opinion Based on current progress in defining cross-protective influenza immunity, it seems that the development of a universal influenza vaccine is feasible. It would revolutionize the strategy for influenza pandemic preparedness, and significantly impact the shelf-life and protection efficacy of seasonal influenza vaccines. PMID:28925296

Influenza infection and heart failure-vaccination may change heart failure prognosis?

PubMed

Kadoglou, Nikolaos P E; Bracke, Frank; Simmers, Tim; Tsiodras, Sotirios; Parissis, John

2017-05-01

The interaction of influenza infection with the pathogenesis of acute heart failure (AHF) and the worsening of chronic heart failure (CHF) is rather complex. The deleterious effects of influenza infection on AHF/CHF can be attenuated by specific immunization. Our review aimed to summarize the efficacy, effectiveness, safety, and dosage of anti-influenza vaccination in HF. In this literature review, we searched MEDLINE and EMBASE from January 1st 1966 to December 31st, 2016, for studies examining the association between AHF/CHF, influenza infections, and anti-influenza immunizations. We used broad criteria to increase the sensitivity of the search. HF was a prerequisite for our search. The search fields used included "heart failure," "vaccination," "influenza," "immunization" along with variants of these terms. No restrictions on the type of study design were applied. The most common clinical scenario is exacerbation of pre-existing CHF by influenza infection. Scarce evidence supports a potential positive association of influenza infection with AHF. Vaccinated patients with pre-existing CHF have reduced all-cause morbidity and mortality, but effects are not consistently documented. Immunization with higher antigen quantity may confer additional protection, but such aggressive approach has not been generally advocated. Further studies are needed to delineate the role of influenza infection on AHF/CHF pathogenesis and maintenance. Annual anti-influenza vaccination appears to be an effective measure for secondary prevention in HF. Better immunization strategies and more efficacious vaccines are urgently necessary.

Variations in Influenza and Pneumonia Immunizations for Medicare Beneficiaries Served by Rural Health Clinics.

PubMed

Wan, Thomas T H; Lin, Yi-Ling; Ortiz, Judith

2017-08-01

The availability of a rural health clinic (RHC) database over the period of 6 years (2008-2013) offers a unique opportunity to examine the trends and patterns of disparities in immunization for influenza and pneumonia among Medicare beneficiaries in the southeastern states. The purpose of this exploratory study was twofold. First, it examined the rural trends and patterns of immunization rates before (2008-2009) and after (2010-2013) the Affordable Care Act (ACA) enactment by state and year. Second, it investigated how contextual, organizational, and aggregate patient characteristics may influence the variations in immunization for influenza and pneumonia of Medicare beneficiaries served by RHCs. Four data sources from federal agencies were merged to perform a longitudinal analysis of the influences of contextual, organizational, and aggregate patient characteristics on the disparities in immunization rates of rural Medicare beneficiaries for influenza and pneumonia. We included both time-varying and time-constant predictors in a multivariate analysis using Generalized Estimating Equation. This study revealed the increased immunization rates for both influenza and pneumonia over a period of 6 years. The ACA had a positive effect on increased immunization rates for pneumonia, but not for influenza, in rural Medicare beneficiaries in the eight states. The RHCs that served more dually-eligible patients had higher immunization rates. For influenza immunization, provider-based RHCs had a higher rate than the independent RHCs. For pneumonia immunization, no organizational variables were relevant in the explanation of the variability. The results also showed that no single dominant factor influenced health care disparities. This investigation suggested further improvements in preventive care are needed to target poor and isolated rural beneficiaries. Furthermore, the integration of immunization data from multiple sources is critically needed for understanding health disparities.

Factors Associated with Seasonal Influenza Immunization among Church-going Older African Americans

PubMed Central

BOGGAVARAPU, Sahithi; SULLIVAN, Kevin M.; SCHAMEL, Jay T.; FREW, Paula M.

2014-01-01

Objectives Churches and faith institutions can frequently influence health behaviors among older African Americans. The church is a centerpiece of spiritual and social life among African American congregants. We explored its influence on influenza immunization coverage during the 2012–2013 influenza season. Methods A cross-sectional study was conducted among congregation members ages 50–89 years from six churches in the Atlanta region in 2013–2014. We computed descriptive statistics, bivariate associations, and multivariable models to examine factors associated with immunization uptake among this population. Results Of 208 study participants, 95 (45.7%) reported receiving the influenza vaccine. Logistic regression showed that increased trust in their healthcare providers’ vaccine recommendations was a positive predictor of vaccination among participants who had not experienced discrimination in a faith-based setting (OR: 14.8 [3.7,59.8]), but was not associated with vaccination for participants who had experienced such discrimination (OR: 1.5 [0.2,7.0]). Belief in vaccine-induced influenza illness (OR: 0.1 [0.05, 0.23]) was a negative predictor of influenza vaccination. Conclusion Members of this older cohort of African Americans who expressed trust in their healthcare providers’ vaccine recommendations and disbelief in vaccine-induced influenza were more likely to obtain seasonal influenza immunization. They were also more likely to act on their trust of healthcare provider’s vaccine recommendations if they did not encounter negative influenza immunization attitudes within the church. Having healthcare providers address negative influenza immunization attitudes and disseminate vaccine information in a culturally appropriate manner within the church has the potential to enhance future uptake of influenza vaccination. PMID:25444831

Maternal Influenza Immunization and Adverse Birth Outcomes: Using Data and Practice to Inform Theory and Research Design.

PubMed

Phadke, Varun K; Steinhoff, Mark C; Omer, Saad B; MacDonald, Noni E

2016-12-01

Maternal influenza immunization can reduce influenza-attributable morbidity and mortality among pregnant women and infants who are too young to be vaccinated. Data from empirical studies also support the hypothesis that immunization can protect the fetus against adverse outcomes if the mother is exposed to influenza. In their theoretical analysis in the Journal, Hutcheon et al. (Am J Epidemiol 2016;184(3):227-232) critiqued the existing evidence of the fetal benefits of maternal influenza immunization by calculating the sample sizes needed to demonstrate hypothetical reductions in risk and concluded that the benefits observed in empirical studies are likely implausible. However, in their analysis, they did not take into account multiple fundamental characteristics of influenza epidemiology, including the time-variable effects of influenza illness and vaccination during pregnancy, or well-known differences in disease epidemiology between seasons, populations, and geographic regions. Although these and other factors might affect the magnitude of fetal benefit conferred by maternal influenza immunization, studies in which investigators have accounted for influenza circulation have demonstrated a consistent protective effect against a variety of adverse birth outcomes; those studies include the only randomized controlled trial designed a priori and adequately powered to do so. Only a comprehensive and nuanced assessment of the evidence base will allow for effective translation of these data into a global immunization policy. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Demonstration of the feasibility of emergency department immunization against influenza and pneumococcus.

PubMed

Slobodkin, D; Zielske, P G; Kitlas, J L; McDermott, M F; Miller, S; Rydman, R

1998-11-01

To demonstrate the feasibility of systematic immunization against influenza and pneumococcus in a public emergency department. This was a demonstration project conducted from October 21, 1996, through December 2, 1996, at Cook County Hospital, an inner-city hospital with a 1996 adult ED census of 120,449. Seventy-eight percent of patients are uninsured; 92% are people of color; 73% deny having a primary physician. Only 15% have emergency complaints. Nurses received standing orders that all nonemergency adult patients meeting Centers for Disease Control and Prevention criteria for high risk should be offered immunization against influenza and pneumococcus at triage. Cash prizes were offered to nurses appropriately immunizing the most patients. The date of immunization was entered into the computerized patient registration system, available to all providers within the county system. From November 4 through November 18, an extra nurse was assigned to triage to test for improvement in immunization rates. A time-motion study determined the time required per immunization on the basis of a convenience sample of 8 nurses drawn from all 3 shifts. Only 3% of identified high-risk patients reported previous pneumococcal immunization. Despite extreme variation in nurse performance, 2,631 patients (24% of patients triaged) were screened, and 716 high-risk patients were identified (27% of patients screened). A total of 1234 patients were immunized against influenza, and 241 patients were appropriately immunized against pneumococcus. Sixty-one percent of high-risk patients with no contraindication to influenza immunization were immunized against influenza. Thirty-five percent of high-risk patients not previously immunized against pneumococcus were immunized against pneumococcus. Immunizations per shift per triage nurse varied from 0 to 24. Median time for all activities related to immunization was 4 minutes (range, 2 to 10 minutes). There was no increase in immunization rates with the addition of an extra nurse at triage (95% confidence interval for odds ratio, .929 to 1.153). Systematic immunization against influenza and pneumococcus is both needed and feasible in a public ED. "Buy-in" by nurses is variable. Increased staffing alone does not improve immunization rates.

Maternal vaccination for the prevention of influenza: current status and hopes for the future

PubMed Central

Phadke, Varun K.; Omer, Saad B.

2016-01-01

Influenza is an important cause of morbidity and mortality among pregnant women and young infants, and influenza infection during pregnancy has also been associated with adverse obstetric and birth outcomes. There is substantial evidence – from randomized trials and observational studies – that maternal influenza immunization can protect pregnant women and their infants from influenza disease. In addition, there is compelling observational evidence that prevention of influenza in pregnant women can also protect against certain adverse pregnancy outcomes, including stillbirth and preterm birth. In this article we will review and evaluate the literature on both the burden of influenza disease in pregnant women and infants, as well as the multiple potential benefits of maternal influenza immunization for mother, fetus, and infant. We will also review key clinical aspects of maternal influenza immunization, as well as identify remaining knowledge gaps, and discuss avenues for future investigation. PMID:27070268

Humoral and Cellular Response in Humans After Immunization with Influenza Vaccine

PubMed Central

Ruben, Frederick L.; Jackson, George G.; Gotoff, Samuel P.

1973-01-01

The peripheral blood lymphocyte response and hemagglutination inhibition antibody titers were measured in nine adults before and after immunization with a killed split influenza virus vaccine. Cord blood lymphocytes were tested with the influenza antigen to exclude a nonspecific mitogenic effect. All of the subjects demonstrated preexisting antibody titers and antigen recognition by lymphocytes prior to immunization. The in vitro lymphocyte response after vaccination parallels the humoral antibody response to influenza antigen. PMID:4762112

Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus.

PubMed

Di Mario, Giuseppina; Soprana, Elisa; Gubinelli, Francesco; Panigada, Maddalena; Facchini, Marzia; Fabiani, Concetta; Garulli, Bruno; Basileo, Michela; Cassone, Antonio; Siccardi, Antonio; Donatelli, Isabella; Castrucci, Maria R

2017-03-01

Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses. Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus. Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge. Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.

Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries.

PubMed

Garcia, Salvador; Lagos, Rosanna; Muñoz, Alma; Picón, Teresa; Rosa, Raquel; Alfonso, Adriana; Abriata, Graciela; Gentile, Angela; Romanin, Viviana; Regueira, Mabel; Chiavetta, Laura; Agudelo, Clara Inés; Castañeda, Elizabeth; De la Hoz, Fernando; Higuera, Ana Betty; Arce, Patricia; Cohen, Adam L; Verani, Jennifer; Zuber, Patrick; Gabastou, Jean-Marc; Pastor, Desiree; Flannery, Brendan; Andrus, Jon

2012-01-05

To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi-country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used. Copyright © 2011 Elsevier Ltd. All rights reserved.

Integrating pharmacies into public health program planning for pandemic influenza vaccine response.

PubMed

Fitzgerald, Thomas J; Kang, Yoonjae; Bridges, Carolyn B; Talbert, Todd; Vagi, Sara J; Lamont, Brock; Graitcer, Samuel B

2016-11-04

During an influenza pandemic, to achieve early and rapid vaccination coverage and maximize the benefit of an immunization campaign, partnerships between public health agencies and vaccine providers are essential. Immunizing pharmacists represent an important group for expanding access to pandemic vaccination. However, little is known about nationwide coordination between public health programs and pharmacies for pandemic vaccine response planning. To assess relationships and planning activities between public health programs and pharmacies, we analyzed data from Centers for Disease Control and Prevention assessments of jurisdictions that received immunization and emergency preparedness funding from 2012 to 2015. Forty-seven (88.7%) of 53 jurisdictions reported including pharmacies in pandemic vaccine distribution plans, 24 (45.3%) had processes to recruit pharmacists to vaccinate, and 16 (30.8%) of 52 established formal relationships with pharmacies. Most jurisdictions plan to allocate less than 10% of pandemic vaccine supply to pharmacies. While most jurisdictions plan to include pharmacies as pandemic vaccine providers, work is needed to establish formalized agreements between public health departments and pharmacies to improve pandemic preparedness coordination and ensure that vaccinating pharmacists are fully utilized during a pandemic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influenza and Memory T Cells: How to Awake the Force

PubMed Central

Spitaels, Jan; Roose, Kenny; Saelens, Xavier

2016-01-01

Annual influenza vaccination is an effective way to prevent human influenza. Current vaccines are mainly focused on eliciting a strain-matched humoral immune response, requiring yearly updates, and do not provide protection for all vaccinated individuals. The past few years, the importance of cellular immunity, and especially memory T cells, in long-lived protection against influenza virus has become clear. To overcome the shortcomings of current influenza vaccines, eliciting both humoral and cellular immunity is imperative. Today, several new vaccines such as infection-permissive and recombinant T cell inducing vaccines, are being developed and show promising results. These vaccines will allow us to stay several steps ahead of the constantly evolving influenza virus. PMID:27754364

Divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated H3N2 swine influenza vaccines in the presence of maternally-derived antibodies

USDA-ARS?s Scientific Manuscript database

Vaccine-associated enhanced respiratory disease (VAERD) can occur in pigs immunized with whole-inactivated influenza virus (WIV) vaccine and subsequently infected with an antigenically divergent virus of the same HA subtype. Live-attenuated influenza virus (LAIV) vaccines administered intranasally h...

Galvanizing medical students in the administration of influenza vaccines: the Stanford Flu Crew.

PubMed

Rizal, Rachel E; Mediratta, Rishi P; Xie, James; Kambhampati, Swetha; Hills-Evans, Kelsey; Montacute, Tamara; Zhang, Michael; Zaw, Catherine; He, Jimmy; Sanchez, Magali; Pischel, Lauren

2015-01-01

Many national organizations call for medical students to receive more public health education in medical school. Nonetheless, limited evidence exists about successful servicelearning programs that administer preventive health services in nonclinical settings. The Flu Crew program, started in 2001 at the Stanford University School of Medicine, provides preclinical medical students with opportunities to administer influenza immunizations in the local community. Medical students consider Flu Crew to be an important part of their medical education that cannot be learned in the classroom. Through delivering vaccines to where people live, eat, work, and pray, Flu Crew teaches medical students about patient care, preventive medicine, and population health needs. Additionally, Flu Crew allows students to work with several partners in the community in order to understand how various stakeholders improve the delivery of population health services. Flu Crew teaches students how to address common vaccination myths and provides insights into implementing public health interventions. This article describes the Stanford Flu Crew curriculum, outlines the planning needed to organize immunization events, shares findings from medical students' attitudes about population health, highlights the program's outcomes, and summarizes the lessons learned. This article suggests that Flu Crew is an example of one viable service-learning modality that supports influenza vaccinations in nonclinical settings while simultaneously benefiting future clinicians.

Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination.

PubMed

Ko, Eun-Ju; Lee, Young-Tae; Lee, Youri; Kim, Ki-Hye; Kang, Sang-Moo

2017-10-01

Monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG are toll-like receptor (TLR) 4 and 9 agonist, respectively. Here, we investigated the effects of MPL, CpG, and combination adjuvants on stimulating in vitro dendritic cells (DCs), in vivo innate and adaptive immune responses, and protective efficacy of influenza vaccination. Combination of MPL and CpG was found to exhibit distinct effects on stimulating DCs in vitro to secrete IL-12p70 and tumor necrosis factor (TNF)-α and proliferate allogeneic CD8 T cells. Prime immunization of mice with inactivated split influenza vaccine in the presence of low dose MPL+CpG adjuvants increased the induction of virus-specific IgG and IgG2a isotype antibodies. MPL and CpG adjuvants contribute to improving the efficacy of prime influenza vaccination against lethal influenza challenge as determined by body weight monitoring, lung function, viral titers, and histology. A combination of MPL and CpG adjuvants was effective in improving vaccine efficacy as well as in reducing inflammatory immune responses locally and in inducing cellular immune responses upon lethal influenza virus challenge. This study demonstrates unique adjuvant effects of MPL, CpG, and combination adjuvants on modulating innate and adaptive immune responses to influenza prime vaccination.

Summary of the National Advisory Committee on Immunization (NACI) Statement on Seasonal Influenza Vaccine for 2016-2017.

PubMed

Gemmill, I; Zhao, L; Cochrane, L

2016-09-01

Influenza is a respiratory infection caused primarily by influenza A and B viruses. Vaccination is the most effective way to prevent influenza and its complications. The National Advisory Committee on Immunization (NACI) provides recommendations regarding seasonal influenza vaccines annually to the Public Health Agency of Canada (the Agency). To summarize the NACI recommendations regarding the use of seasonal influenza vaccines for the 2016-2017 influenza season. Annual influenza vaccine recommendations are developed by NACI's Influenza Working Group for consideration and approval by NACI, based on NACI's evidence-based process for developing recommendations, and include a consideration of the burden of influenza illness and the target populations for vaccination; efficacy and effectiveness, immunogenicity and safety of influenza vaccines; vaccine schedules; and other aspects of influenza immunization. These recommendations are published annually on the Agency's website in the NACI Advisory Committee Statement: Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine (the Statement). The annual NACI seasonal influenza vaccine recommendations have been updated for the 2016-2017 influenza season to include adults with neurologic or neurodevelopment conditions among the groups for whom influenza vaccination is particularly recommended; to include the new high-dose, trivalent inactivated influenza vaccine for use in adults 65 years of age and over; to recommend that egg-allergic individuals may also be vaccinated against influenza using the low ovalbumin-containing live attenuated influenza vaccine (LAIV) licensed for use in Canada (NACI has previously recommended that egg-allergic individuals may be vaccinated using inactivated influenza vaccines); and to remove the preferential recommendation for the use of LAIV in children 2-17 years of age. Two addenda to the 2016-2017 Statement address these new LAIV recommendations. NACI continues to recommend annual influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk and others as indicated.

Controlling Influenza by Cytotoxic T-Cells: Calling for Help from Destroyers

PubMed Central

Schotsaert, Michael; Ibañez, Lorena Itatí; Fiers, Walter; Saelens, Xavier

2010-01-01

Influenza is a vaccine preventable disease that causes severe illness and excess mortality in humans. Licensed influenza vaccines induce humoral immunity and protect against strains that antigenically match the major antigenic components of the vaccine, but much less against antigenically diverse influenza strains. A vaccine that protects against different influenza viruses belonging to the same subtype or even against viruses belonging to more than one subtype would be a major advance in our battle against influenza. Heterosubtypic immunity could be obtained by cytotoxic T-cell (CTL) responses against conserved influenza virus epitopes. The molecular mechanisms involved in inducing protective CTL responses are discussed here. We also focus on CTL vaccine design and point to the importance of immune-related databases and immunoinformatics tools in the quest for new vaccine candidates. Some techniques for analysis of T-cell responses are also highlighted, as they allow estimation of cellular immune responses induced by vaccine preparations and can provide correlates of protection. PMID:20508820

Making evidence-based selections of influenza vaccines.

PubMed

Childress, Billy-Clyde; Montney, Joshua D; Albro, Elise A

2014-01-01

Years ago, intramuscular influenza vaccines were the only option for those who wanted to arm themselves against the flu. Today there are alternatives, including intradermal injections and intranasal sprays. In order to select the right influenza vaccine for their patients, pharmacists, and other healthcare professionals must have a basic understanding of the immune system. Influenza vaccines elicit different levels of immune response involving innate and adaptive immunity, which are critical to fighting infection. For the 2013-2014 flu season, there were 13 different formulations of influenza vaccines on the market with vast differences in indications, contraindications, and effectiveness. The CDC does not recommend one vaccine over another, but recommends that all patients be vaccinated against the flu. Preventing the spread of influenza is no simple task; however, the most recent evidence on influenza vaccines and sufficient knowledge of the immune system will allow pharmacists and other healthcare providers to better advocate for vaccines, determine which are most appropriate, and ensure their proper administration.

A dual purpose universal influenza vaccine candidate confers protective immunity against anthrax.

PubMed

Arévalo, Maria T; Li, Junwei; Diaz-Arévalo, Diana; Chen, Yanping; Navarro, Ashley; Wu, Lihong; Yan, Yongyong; Zeng, Mingtao

2017-03-01

Preventive influenza vaccines must be reformulated annually because of antigen shift and drift of circulating influenza viral strains. However, seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to humans. Hence, a universal influenza vaccine is needed to provide protective immunity against a broad range of influenza viruses. We designed an influenza antigen consisting of three tandem M2e repeats plus HA2, in combination with a detoxified anthrax oedema toxin delivery system (EFn plus PA) to enhance immune responses. The EFn-3×M2e-HA2 plus PA vaccine formulation elicited robust, antigen-specific, IgG responses; and was protective against heterologous influenza viral challenge when intranasally delivered to mice three times. Moreover, use of the detoxified anthrax toxin system as an adjuvant had the additional benefit of generating protective immunity against anthrax. Hence, this novel vaccine strategy could potentially address two major emerging public health and biodefence threats. © 2016 John Wiley & Sons Ltd.

Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach.

PubMed

Lambert, Nathaniel D; Ovsyannikova, Inna G; Pankratz, V Shane; Jacobson, Robert M; Poland, Gregory A

2012-08-01

Annual vaccination against seasonal influenza is recommended to decrease disease-related mortality and morbidity. However, one population that responds suboptimally to influenza vaccine is adults over the age of 65 years. The natural aging process is associated with a complex deterioration of multiple components of the host immune system. Research into this phenomenon, known as immunosenescence, has shown that aging alters both the innate and adaptive branches of the immune system. The intricate mechanisms involved in immune response to influenza vaccine, and how these responses are altered with age, have led us to adopt a more encompassing systems biology approach to understand exactly why the response to vaccination diminishes with age. Here, the authors review what changes occur with immunosenescence, and some immunogenetic factors that influence response, and outline the systems biology approach to understand the immune response to seasonal influenza vaccination in older adults.

Three randomized trials of maternal influenza immunization in Mali, Nepal, and South Africa: Methods and expectations.

PubMed

Omer, Saad B; Richards, Jennifer L; Madhi, Shabir A; Tapia, Milagritos D; Steinhoff, Mark C; Aqil, Anushka R; Wairagkar, Niteen

2015-07-31

Influenza infection in pregnancy can have adverse impacts on maternal, fetal, and infant outcomes. Influenza vaccination in pregnancy is an appealing strategy to protect pregnant women and their infants. The Bill & Melinda Gates Foundation is supporting three large, randomized trials in Nepal, Mali, and South Africa evaluating the efficacy and safety of maternal immunization to prevent influenza disease in pregnant women and their infants <6 months of age. Results from these individual studies are expected in 2014 and 2015. While the results from the three maternal immunization trials are likely to strengthen the evidence base regarding the impact of influenza immunization in pregnancy, expectations for these results should be realistic. For example, evidence from previous influenza vaccine studies - conducted in general, non-pregnant populations - suggests substantial geographic and year-to-year variability in influenza incidence and vaccine efficacy/effectiveness. Since the evidence generated from the three maternal influenza immunization trials will be complementary, in this paper we present a side-by-side description of the three studies as well as the similarities and differences between these trials in terms of study location, design, outcome evaluation, and laboratory and epidemiological methods. We also describe the likely remaining knowledge gap after the results from these trials become available along with a description of the analyses that will be conducted when the results from these individual data are pooled. Moreover, we highlight that additional research on logistics of seasonal influenza vaccine supply, surveillance and strain matching, and optimal delivery strategies for pregnant women will be important for informing global policy related to maternal influenza immunization. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature

PubMed Central

Vassilieva, Elena V.; Kalluri, Haripriya; McAllister, Devin; Taherbhai, Misha T.; Esser, E. Stein; Pewin, Winston P.; Pulit-Penaloza, Joanna A.; Prausnitz, Mark R.; Compans, Richard W.; Skountzou, Ioanna

2015-01-01

Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study we evaluated the immunogenicity of H1N1, H3N2 and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25°C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by SRID assay and immune responses to vaccination in BALB/c mice. After a single immunization all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least three months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability. PMID:25895053

Estradiol and progesterone influence on influenza infection and immune response in a mouse model.

PubMed

Davis, Sarah M; Sweet, Leigh M; Oppenheimer, Karen H; Suratt, Benjamin T; Phillippe, Mark

2017-10-01

Influenza infection severity may be mediated by estradiol and/or progesterone. An exploratory study was designed to evaluate 17-β-estradiol and progesterone on influenza infection and examine immune-mediated response in a mouse model. Inoculation with placebo or mouse-adapted H1N1 influenza virus occurred. Treatment groups included 17-β-estradiol, progesterone, ovariectomy, and pregnancy. Mice were assessed for morbidity and mortality. Toll-like receptor gene studies and airspace cell differentials were performed. Onset of morbidity was earlier and morbidity duration greater for progesterone. Absence of morbidity/mortality and overall survival was greater for 17-β-estradiol. Airspace cell differentials suggest improved immune cell recruitment for 17-β-estradiol. Pregnant mouse data demonstrate significant mortality during the period of increased progesterone. Select immune cell markers demonstrate patterns of regulation that may promote proper immune response to influenza infection for 17-β-estradiol. Estradiol may play a protective and progesterone a detrimental role in the pathophysiology of influenza infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vaccine epidemiology: Its role in promoting sound immunization programs in Japan.

PubMed

Hirota, Yoshio; Ozasa, Kotaro; Nakano, Takashi

2017-08-24

In Japan, the Vaccine Epidemiology Research Group created by the Ministry of Health, Labour and Welfare has played an important role in demonstrating the solid scientific basis for vaccine efficacy and safety since 2002. Members of the group, including epidemiologists, clinicians and microbiologists, have been conducting collaborative studies on vaccines for influenza, pertussis, rotavirus gastroenteritis, polio and pneumonia. So far, the group has achieved several works and contributed to the national vaccination program, including research on the immunogenicity of low doses of influenza vaccine among young children, the immunogenicity and effectiveness of the 2009 influenza pandemic vaccine among various risk groups, the interchangeability of live/inactivated polio vaccines, the health impact of influenza on pregnant women, and the monitoring of influenza vaccine effectiveness using case-control studies with a test-negative design. As part of the 18th Annual Meeting of the Japanese Society of Vaccinology, these accomplishments were featured in the Vaccine Epidemiology Symposium. This report summarizes the recent epidemiological studies on vaccine in Japan as a prologue to the next six papers collected from the symposium. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bacillus Calmette-Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice.

PubMed

de Bree, Charlotte L C J; Marijnissen, Renoud J; Kel, Junda M; Rosendahl Huber, Sietske K; Aaby, Peter; Benn, Christine Stabell; Wijnands, Marcel V W; Diavatopoulos, Dimitri A; van Crevel, Reinout; Joosten, Leo A B; Netea, Mihai G; Dulos, John

2018-01-01

Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak. Bacillus Calmette-Guérin (BCG) is known to induce strong heterologous immunological effects, and it has been shown that BCG protects against non-related infection challenges in several mouse models. BCG immunization of mice as well as human induces trained innate immune responses, resulting in increased cytokine responses upon subsequent ex vivo peripheral blood mononuclear cell restimulation. We investigated whether BCG (Statens Serum Institut-Denmark)-induced trained immunity may protect against a lethal avian influenza A/Anhui/1/2013 (H7N9) challenge. Here, we show that isolated splenocytes as well as peritoneal macrophages of BCG-immunized BALB/c mice displayed a trained immunity phenotype resulting in increased innate cytokine responses upon ex vivo restimulation. However, after H7N9 infection, no significant differences were found between the BCG immunized and the vehicle control group at the level of survival, weight loss, pulmonary influenza A nucleoprotein staining, or histopathology. In conclusion, BCG-induced trained immunity did not result in protection in an oseltamivir-sensitive influenza A/Anhui/1/2013 (H7N9) challenge mouse model.

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

PubMed

Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

2009-08-06

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the existence of pre-existing heterosubtypic immunity may dampen the impact a future influenza pandemic may have.

Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination

PubMed Central

Ko, Eun-Ju; Lee, Young-Tae; Lee, Youri; Kim, Ki-Hye

2017-01-01

Monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG are toll-like receptor (TLR) 4 and 9 agonist, respectively. Here, we investigated the effects of MPL, CpG, and combination adjuvants on stimulating in vitro dendritic cells (DCs), in vivo innate and adaptive immune responses, and protective efficacy of influenza vaccination. Combination of MPL and CpG was found to exhibit distinct effects on stimulating DCs in vitro to secrete IL-12p70 and tumor necrosis factor (TNF)-α and proliferate allogeneic CD8 T cells. Prime immunization of mice with inactivated split influenza vaccine in the presence of low dose MPL+CpG adjuvants increased the induction of virus-specific IgG and IgG2a isotype antibodies. MPL and CpG adjuvants contribute to improving the efficacy of prime influenza vaccination against lethal influenza challenge as determined by body weight monitoring, lung function, viral titers, and histology. A combination of MPL and CpG adjuvants was effective in improving vaccine efficacy as well as in reducing inflammatory immune responses locally and in inducing cellular immune responses upon lethal influenza virus challenge. This study demonstrates unique adjuvant effects of MPL, CpG, and combination adjuvants on modulating innate and adaptive immune responses to influenza prime vaccination. PMID:29093654

Lessons learned: role of influenza vaccine production, distribution, supply, and demand--what it means for the provider.

PubMed

Orenstein, Walter A; Schaffner, William

2008-07-01

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) has been increasing the size of the population for whom influenza vaccine is recommended to reduce the substantial and persistent annual health burden of influenza. Realization of current and future public health influenza immunization goals requires assuring vaccine supply will be adequate to meet demand. This has posed distinct challenges for the many stakeholders in the influenza vaccine program--government agencies, federal, state, and local policymakers, vaccine manufacturers and distributors, and the medical community--each of whom must make critical decisions in a constantly shifting environment. Factors such as the yearly changes in influenza virus strains, the complicated vaccine production and distribution process, revisions in vaccination recommendations, and changing demographics can all affect the delicate balance between supply and demand. While vaccine shortages and delays have been well-publicized concerns in the recent past, there has been a marked increase in supply in the past several years, with substantial growth in supply expected in the future. The primary issue today is to strengthen the demand for the influenza vaccine, which would in turn help ensure the continued availability of the vaccine to reduce disease burden. A number of strategies are discussed, including increased efforts to publicize and fully implement current CDC recommendations and to offer influenza vaccine beyond the typical vaccination season of October and November, because in the great majority of years, vaccination into January and beyond will still provide health benefits.

Marketing paediatric influenza vaccination: results of a major metropolitan trial.

PubMed

Van Buynder, Paul G; Carcione, Dale; Rettura, Vince; Daly, Alison; Woods, Emily

2011-01-01

After a cluster of rapidly fulminant influenza related toddler deaths in a Western Australian metropolis, children aged six to 59 months were offered influenza vaccination in subsequent winters. Some parental resistance was expected and previous poor uptake of paediatric influenza vaccination overseas was noted. A marketing campaign addressing barriers to immunization was developed to maximise uptake. Advertising occurred in major statewide newspapers, via public poster displays and static 'eye-lite' displays, via press releases, via a series of rolling radio advertisements, via direct marketing to child care centres, and via a linked series of web-sites. Parents were subsequently surveyed to assess reasons for vaccination. The campaign produced influenza vaccination coverage above that previously described elsewhere and led to a proportionate reduction in influenza notifications in this age group compared to previous seasons. Influenza in children comes with significant morbidity and some mortality. Paediatric influenza vaccination is safe, well tolerated and effective if two doses are given. A targeted media campaign can increase vaccine uptake if it reinforces the seriousness of influenza and addresses community 'myths' about influenza and influenza vaccine. The lessons learned enabling enhancements of similar programs elsewhere. © 2010 Blackwell Publishing Ltd.

A Candidate H1N1 Pandemic Influenza Vaccine Elicits Protective Immunity in Mice

PubMed Central

Steitz, Julia; Barlow, Peter G.; Hossain, Jaber; Kim, Eun; Okada, Kaori; Kenniston, Tom; Rea, Sheri; Donis, Ruben O.; Gambotto, Andrea

2010-01-01

Background In 2009 a new pandemic disease appeared and spread globally. The recent emergence of the pandemic influenza virus H1N1 first isolated in Mexico and USA raised concerns about vaccine availability. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model. Methods We generated two adenovirus(Ad5)-based influenza vaccine candidates encoding the wildtype or a codon-optimized hemagglutinin antigen (HA) from the recently emerged swine influenza isolate A/California/04/2009 (H1N1)pdm. After verification of antigen expression, immunogenicity of the vaccine candidates were tested in a mouse model using dose escalations for subcutaneous immunization. Sera of immunized animals were tested in microneutalization and hemagglutination inhibition assays for the presence of HA-specific antibodies. HA-specific T-cells were measured in IFNγ Elispot assays. The efficiency of the influenza vaccine candidates were evaluated in a challenge model by measuring viral titer in lung and nasal turbinate 3 days after inoculation of a homologous H1N1 virus. Conclusions/Significance A single immunization resulted in robust cellular and humoral immune response. Remarkably, the intensity of the immune response was substantially enhanced with codon-optimized antigen, indicating the benefit of manipulating the genetic code of HA antigens in the context of recombinant influenza vaccine design. These results highlight the value of advanced technologies in vaccine development and deployment in response to infections with pandemic potential. Our study emphasizes the potential of an adenoviral-based influenza vaccine platform with the benefits of speed of manufacture and efficacy of a single dose immunization. PMID:20463955

Cooperativity Between CD8+ T Cells, Non-Neutralizing Antibodies, and Alveolar Macrophages Is Important for Heterosubtypic Influenza Virus Immunity

PubMed Central

Laidlaw, Brian J.; Decman, Vilma; Ali, Mohammed-Alkhatim A.; Abt, Michael C.; Wolf, Amaya I.; Monticelli, Laurel A.; Mozdzanowska, Krystyna; Angelosanto, Jill M.; Artis, David; Erikson, Jan; Wherry, E. John

2013-01-01

Seasonal epidemics of influenza virus result in ∼36,000 deaths annually in the United States. Current vaccines against influenza virus elicit an antibody response specific for the envelope glycoproteins. However, high mutation rates result in the emergence of new viral serotypes, which elude neutralization by preexisting antibodies. T lymphocytes have been reported to be capable of mediating heterosubtypic protection through recognition of internal, more conserved, influenza virus proteins. Here, we demonstrate using a recombinant influenza virus expressing the LCMV GP33-41 epitope that influenza virus-specific CD8+ T cells and virus-specific non-neutralizing antibodies each are relatively ineffective at conferring heterosubtypic protective immunity alone. However, when combined virus-specific CD8 T cells and non-neutralizing antibodies cooperatively elicit robust protective immunity. This synergistic improvement in protective immunity is dependent, at least in part, on alveolar macrophages and/or other lung phagocytes. Overall, our studies suggest that an influenza vaccine capable of eliciting both CD8+ T cells and antibodies specific for highly conserved influenza proteins may be able to provide heterosubtypic protection in humans, and act as the basis for a potential “universal” vaccine. PMID:23516357

Resource utilization and cost of influenza requiring hospitalization in Canadian adults: A study from the serious outcomes surveillance network of the Canadian Immunization Research Network.

PubMed

Ng, Carita; Ye, Lingyun; Noorduyn, Stephen G; Hux, Margaret; Thommes, Edward; Goeree, Ron; Ambrose, Ardith; Andrew, Melissa K; Hatchette, Todd; Boivin, Guy; Bowie, William; ElSherif, May; Green, Karen; Johnstone, Jennie; Katz, Kevin; Leblanc, Jason; Loeb, Mark; MacKinnon-Cameron, Donna; McCarthy, Anne; McElhaney, Janet; McGeer, Allison; Poirier, Andre; Powis, Jeff; Richardson, David; Sharma, Rohita; Semret, Makeda; Smith, Stephanie; Smyth, Daniel; Stiver, Grant; Trottier, Sylvie; Valiquette, Louis; Webster, Duncan; McNeil, Shelly A

2018-03-01

Consideration of cost determinants is crucial to inform delivery of public vaccination programs. To estimate the average total cost of laboratory-confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs. Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory-confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 to 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions. Dataset included 2943 adult admissions to 17 SOS Network hospitals and 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8), and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14 612 CAD (95% CI: $13 852, $15 372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14 031 (95% CI: $13 295, $14 768) during initial hospital stay, $447 (95% CI: $271, $624) post-discharge, including readmission within 30 days. The cost of laboratory-confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory-confirmed influenza cases. The true per-patient cost of influenza-related hospitalization has been underestimated, and prevention programs should be evaluated in this context. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination in the United States: Systematic review.

PubMed

Kang, Gloria J; Culp, Rachel K; Abbas, Kaja M

2017-04-11

The study objective was to identify facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination in the United States. In 2009, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention expanded their recommendations for influenza vaccination to include school-aged children. We conducted a systematic review of studies focused on facilitators and barriers of parental attitudes toward school-located influenza vaccination in the United States from 1990 to 2016. We reviewed 11 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Facilitators were free/low cost vaccination; having belief in vaccine efficacy, influenza severity, and susceptibility; belief that vaccination is beneficial, important, and a social norm; perception of school setting advantages; trust; and parental presence. Barriers were cost; concerns regarding vaccine safety, efficacy, equipment sterility, and adverse effects; perception of school setting barriers; negative physician advice of contraindications; distrust in vaccines and school-located vaccination programs; and health information privacy concerns. We identified the facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination to assist in the evidence-based design and implementation of influenza vaccination programs targeted for children in the United States and to improve influenza vaccination coverage for population-wide health benefits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Seasonal influenza vaccines.

PubMed

Fiore, Anthony E; Bridges, Carolyn B; Cox, Nancy J

2009-01-01

Influenza vaccines are the mainstay of efforts to reduce the substantial health burden from seasonal influenza. Inactivated influenza vaccines have been available since the 1940s and are administered via intramuscular injection. Inactivated vaccines can be given to anyone six months of age or older. Live attenuated, cold-adapted influenza vaccines (LAIV) were developed in the 1960s but were not licensed in the United States until 2003, and are administered via nasal spray. Both vaccines are trivalent preparations grown in eggs and do not contain adjuvants. LAIV is licensed for use in the United States for healthy nonpregnant persons 2-49 years of age.Influenza vaccination induces antibodies primarily against the major surface glycoproteins hemagglutinin (HA) and neuraminidase (NA); antibodies directed against the HA are most important for protection against illness. The immune response peaks at 2-4 weeks after one dose in primed individuals. In previously unvaccinated children <9 years of age, two doses of influenza vaccine are recommended, as some children in this age group have limited or no prior infections from circulating types and subtypes of seasonal influenza. These children require both an initial priming dose and a subsequent booster dose of vaccine to mount a protective antibody response.The most common adverse events associated with inactivated vaccines are sore arm and redness at the injection site; systemic symptoms such as fever or malaise are less commonly reported. Guillian-Barré Syndrome (GBS) was identified among approximately 1 per 100,000 recipients of the 1976 swine influenza vaccine. The risk of influenza vaccine-associated GBS from seasonal influenza vaccine is thought to be at most approximately 1-2 cases per 1 million vaccinees, based on a few studies that have found an association; other studies have found no association.The most common adverse events associated with LAIV are nasal congestion, headache, myalgias or fever. Studies of the safety of LAIV among young children suggest an increased risk of wheezing in some young children, and the vaccine is not recommended for children younger than 2 years old, ages 2-4 old with a history of recurrent wheezing or reactive airways disease, or older persons who have any medical condition that confers an increased risk of influenza-related complications.The effectiveness of influenza vaccines is related predominantly to the age and immune competence of the vaccinee and the antigenic relatedness of vaccine strains to circulating strains. Vaccine effectiveness in preventing laboratory-confirmed influenza illness when the vaccine strains are well matched to circulating strains is 70-90% in randomized, placebo-controlled trials conducted among children and young healthy adults, but is lower among elderly or immunocompromised persons. In years with a suboptimal match, vaccine benefit is likely to be lower, although the vaccine can still provide substantial benefit, especially against more severe outcomes. Live, attenuated influenza vaccines have been most extensively studied among children, and have been shown to be more effective than inactivated vaccines in several randomized controlled trials among young children.Influenza vaccination is recommended in the United States for all children six months or older, all adults 50 years or older, all persons with chronic medical conditions, and pregnant women, and contacts of these persons, including healthcare workers. The global disease burden of influenza is substantial, and the World Health Organization has indicated that member states should evaluate the cost-effectiveness of introducing influenza vaccination into national immunization programs. More research is needed to develop more effective seasonal influenza vaccines that provide long-lasting immunity and broad protection against strains that differ antigenically from vaccine viruses.

A national examination of pharmacy-based immunization statutes and their association with influenza vaccinations and preventive health.

PubMed

McConeghy, Kevin W; Wing, Coady

2016-06-24

A series of state-level statute changes have allowed pharmacists to provide influenza vaccinations in community pharmacies. The study aim was to estimate the effects of pharmacy-based immunization statutes changes on per capita influenza vaccine prescriptions, adult vaccination rates, and the utilization of other preventive health services. A quasi-experimental study that compares vaccination outcomes over time before and after states allowed pharmacy-based immunization. Measures of per capita pharmacy prescriptions for influenza vaccines in each state came from a proprietary pharmacy prescription database. Data on adult vaccination rates and preventive health utilization were studied using multiple waves of the Behavioral Risk Factor Surveillance System (BRFSS). The primary outcomes were changes in per capita influenza vaccine pharmacy prescriptions, adult vaccination rates, and preventive health interventions following changes. Between 2007 and 2013, the number of influenza vaccinations dispensed in community pharmacies increased from 3.2 to 20.9 million. After one year, adopting pharmacist immunization statutes increased per capita influenza vaccine prescriptions by an absolute difference (AD) of 2.6% (95% CI: 1.1-4.2). Adopting statutes did not lead to a significant absolute increase in adult vaccination rates (AD 0.9%, 95% CI: -0.3, 2.2). There also was no observed difference in adult vaccination rates among adults at high-risk of influenza complications (AD 0.8%, 95% CI: -0.2, 1.8) or among standard demographic subgroups. There also was no observed difference in the receipt of preventive health services, including routine physician office visits (AD -1.9%, 95% CI: -4.9, 1.1). Pharmacists are providing millions of influenza vaccines as a consequence of immunization statutes, but we do not observe significant differences in adult influenza vaccination rates. The main gains from pharmacy-based immunization may be in providing a more convenient way to obtain an important health service. Published by Elsevier Ltd.

Impacts of a mass vaccination campaign against pandemic H1N1 2009 influenza in Taiwan: a time-series regression analysis.

PubMed

Wu, Un-In; Wang, Jann-Tay; Chang, Shan-Chwen; Chuang, Yu-Chung; Lin, Wei-Ru; Lu, Min-Chi; Lu, Po-Liang; Hu, Fu-Chang; Chuang, Jen-Hsiang; Chen, Yee-Chun

2014-06-01

A multicenter, hospital-wide, clinical and epidemiological study was conducted to assess the effectiveness of the mass influenza vaccination program during the 2009 H1N1 influenza pandemic, and the impact of the prioritization strategy among people at different levels of risk. Among the 34 359 medically attended patients who displayed an influenza-like illness and had a rapid influenza diagnostic test (RIDT) at one of the three participating hospitals, 21.0% tested positive for influenza A. The highest daily number of RIDT-positive cases in each hospital ranged from 33 to 56. A well-fitted multiple linear regression time-series model (R(2)=0.89) showed that the establishment of special community flu clinics averted an average of nine cases daily (p=0.005), and an increment of 10% in daily mean level of population immunity against pH1N1 through vaccination prevented five cases daily (p<0.001). Moreover, the regression model predicted five-fold or more RIDT-positive cases if the mass influenza vaccination program had not been implemented, and 39.1% more RIDT-positive cases if older adults had been prioritized for vaccination above school-aged children. Mass influenza vaccination was an effective control measure, and school-aged children should be assigned a higher priority for vaccination than older adults during an influenza pandemic. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mechanisms of Cross-protection by Influenza Virus M2-based Vaccines.

PubMed

Lee, Yu-Na; Kim, Min-Chul; Lee, Young-Tae; Kim, Yu-Jin; Kang, Sang-Moo

2015-10-01

Current influenza virus vaccines are based on strain-specific surface glycoprotein hemagglutinin (HA) antigens and effective only when the predicted vaccine strains and circulating viruses are well-matched. The current strategy of influenza vaccination does not prevent the pandemic outbreaks and protection efficacy is reduced or ineffective if mutant strains emerge. It is of high priority to develop effective vaccines and vaccination strategies conferring a broad range of cross protection. The extracellular domain of M2 (M2e) is highly conserved among human influenza A viruses and has been utilized to develop new vaccines inducing cross protection against different subtypes of influenza A virus. However, immune mechanisms of cross protection by M2e-based vaccines still remain to be fully elucidated. Here, we review immune correlates and mechanisms conferring cross protection by M2e-based vaccines. Molecular and cellular immune components that are known to be involved in M2 immune-mediated protection include antibodies, B cells, T cells, alveolar macrophages, Fc receptors, complements, and natural killer cells. Better understanding of protective mechanisms by immune responses induced by M2e vaccination will help facilitate development of broadly cross protective vaccines against influenza A virus.

Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis▿

PubMed Central

Mao, Huawei; Tu, Wenwei; Qin, Gang; Law, Helen Ka Wai; Sia, Sin Fun; Chan, Ping-Lung; Liu, Yinping; Lam, Kwok-Tai; Zheng, Jian; Peiris, Malik; Lau, Yu-Lung

2009-01-01

Influenza is an acute respiratory viral disease that is transmitted in the first few days of infection. Evasion of host innate immune defenses, including natural killer (NK) cells, is important for the virus's success as a pathogen of humans and other animals. NK cells encounter influenza viruses within the microenvironment of infected cells and are important for host innate immunity during influenza virus infection. It is therefore important to investigate the direct effects of influenza virus on NK cells. In this study, we demonstrated for the first time that influenza virus directly infects and replicates in primary human NK cells. Viral entry into NK cells was mediated by both clathrin- and caveolin-dependent endocytosis rather than through macropinocytosis and was dependent on the sialic acids on cell surfaces. In addition, influenza virus infection induced a marked apoptosis of NK cells. Our findings suggest that influenza virus can directly target and kill NK cells, a potential novel strategy of influenza virus to evade the NK cell innate immune defense that is likely to facilitate viral transmission and may also contribute to virus pathogenesis. PMID:19587043

Contribution of antibody production against neuraminidase to the protection afforded by influenza vaccines

PubMed Central

Marcelin, Glendie; Sandbulte, Matthew R.; Webby, Richard J.

2012-01-01

SUMMARY Vaccines are instrumental in controlling the burden of influenza virus infection in humans and animals. Antibodies raised against both major viral surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), can contribute to protective immunity. Vaccine-induced HA antibodies have been characterized extensively, and they generally confer protection by blocking the attachment and fusion of a homologous virus onto host cells. Though not as well characterized, some functions of NA antibodies in influenza vaccine-mediated immunity have been recognized for many years. In this review we summarize the case for NA antibodies in influenza vaccine-mediated immunity. In the absence of well-matched HA antibodies, NA antibodies can provide varying degrees of protection against disease. NA proteins of seasonal influenza vaccines have been shown in some instances to elicit serum antibodies with cross-reactivity to avian- and swine-origin influenza strains, in addition to HA drift variants. NA-mediated immunity has been linked to [i] conserved NA epitopes amongst otherwise antigenically distinct strains, partly attributable to the segmented influenza viral genome; [ii] inhibition of NA enzymatic activity; and [iii] the NA content in vaccine formulations. There is potential to enhance the effectiveness of existing and future influenza vaccines by focusing greater attention on the antigenic characteristics and potency of the NA protein. PMID:22438243

Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

PubMed Central

Ascough, Stephanie; Paterson, Suzanna; Chiu, Christopher

2018-01-01

Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and functionality. Here, we discuss the differences in clinical outcome and immune response following influenza and RSV. Specifically, we focus on differences in their recognition by innate immunity; the strategies used by each virus to evade these early immune responses; and effects across the innate-adaptive interface that may prevent long-lived memory generation. Thus, by comparing these globally important pathogens, we highlight mechanisms by which optimal antiviral immunity may be better induced and discuss the potential for these insights to inform novel vaccines. PMID:29552008

Influenza Vaccine Effectiveness in the Elderly Based on Administrative Databases: Change in Immunization Habit as a Marker for Bias

PubMed Central

Hottes, Travis S.; Skowronski, Danuta M.; Hiebert, Brett; Janjua, Naveed Z.; Roos, Leslie L.; Van Caeseele, Paul; Law, Barbara J.; De Serres, Gaston

2011-01-01

Background Administrative databases provide efficient methods to estimate influenza vaccine effectiveness (IVE) against severe outcomes in the elderly but are prone to intractable bias. This study returns to one of the linked population databases by which IVE against hospitalization and death in the elderly was first assessed. We explore IVE across six more recent influenza seasons, including periods before, during, and after peak activity to identify potential markers for bias. Methods and Findings Acute respiratory hospitalization and all-cause mortality were compared between immunized/non-immunized community-dwelling seniors ≥65years through administrative databases in Manitoba, Canada between 2000-01 and 2005-06. IVE was compared during pre-season/influenza/post-season periods through logistic regression with multivariable adjustment (age/sex/income/residence/prior influenza or pneumococcal immunization/medical visits/comorbidity), stratification based on prior influenza immunization history, and propensity scores. Analysis during pre-season periods assessed baseline differences between immunized and unimmunized groups. The study population included ∼140,000 seniors, of whom 50–60% were immunized annually. Adjustment for key covariates and use of propensity scores consistently increased IVE. Estimates were paradoxically higher pre-season and for all-cause mortality vs. acute respiratory hospitalization. Stratified analysis showed that those twice consecutively and currently immunized were always at significantly lower hospitalization/mortality risk with odds ratios (OR) of 0.60 [95%CI0.48–0.75] and 0.58 [0.53–0.64] pre-season and 0.77 [0.69–0.86] and 0.71 [0.66–0.77] during influenza circulation, relative to the consistently unimmunized. Conversely, those forgoing immunization when twice previously immunized were always at significantly higher hospitalization/mortality risk with OR of 1.41 [1.14–1.73] and 2.45 [2.21–2.72] pre-season and 1.21 [1.03–1.43] and 1.78 [1.61–1.96] during influenza circulation. Conclusions The most pronounced IVE estimates were paradoxically observed pre-season, indicating bias tending to over-estimate vaccine protection. Change in immunization habit from that of the prior two years may be a marker for this bias in administrative data sets; however, no analytic technique explored could adjust for its influence. Improved methods to achieve valid interpretation of protection in the elderly are needed. PMID:21818350

Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic

PubMed Central

2014-01-01

Background Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009–2010. Methods Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test. Results Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms. Conclusions Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain. PMID:24916787

Personal choice or evidence-based nursing intervention: nurses' decision-making about influenza vaccination.

PubMed

Rhudy, Lori M; Tucker, Sharon J; Ofstead, Cori L; Poland, Gregory A

2010-06-01

Nursing interventions are actions taken by nurses to enhance patient outcomes. Little is known about nursing interventions such as influenza vaccination in which the nurse's decision to adopt a health behavior impacts patient outcomes. There is strong evidence that immunization of health care workers (HCWs) against influenza is effective in preventing the spread of this disease and lowers mortality among patients. Yet, worldwide influenza vaccination rates among HCWs are low, with nurse vaccination rates among the lowest. To understand the factors influencing nurses' decision-making about personally receiving immunization against influenza. A qualitative descriptive design in which data were collected using semistructured interviews was used. Participants were 14 RNs who indicated on a prior survey that they were uncertain about, or would not receive an influenza vaccine during the next vaccination season. Data were analyzed using content analysis. The overarching theme is that influenza immunization is a low priority for nurses. Subthemes include a sense of good health, skepticism of the vaccine's value, fear of vaccine side effects, hand washing as prevention, and inconvenient immunization locations. The nurse participants in this study viewed influenza vaccination as a personal health choice, not as an evidence-based nursing intervention. As a result, the decision to decline influenza vaccination was made in the context of personal health choice and/or risk of injury or illness to the nurse. Patient safety outcomes were not expressed as a factor in making the decision to decline influenza vaccination.

Correlation of Cellular Immune Responses with Protection against Culture-Confirmed Influenza Virus in Young Children▿

PubMed Central

Forrest, Bruce D.; Pride, Michael W.; Dunning, Andrew J.; Capeding, Maria Rosario Z.; Chotpitayasunondh, Tawee; Tam, John S.; Rappaport, Ruth; Eldridge, John H.; Gruber, William C.

2008-01-01

The highly sensitive gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay permits the investigation of the role of cell-mediated immunity (CMI) in the protection of young children against influenza. Preliminary studies of young children confirmed that the IFN-γ ELISPOT assay was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to <36 months, an intranasal dose of 107 fluorescent focus units (FFU) of a live attenuated influenza virus vaccine (CAIV-T) elicited substantial CMI responses. A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination. The role of CMI in actual protection against community-acquired, culture-confirmed clinical influenza by CAIV-T was investigated in a large randomized, double-blind, placebo-controlled dose-ranging efficacy trial with 2,172 children aged 6 to <36 months in the Philippines and Thailand. The estimated protection curve indicated that the majority of infants and young children with ≥100 spot-forming cells/106 peripheral blood mononuclear cells were protected against clinical influenza, establishing a possible target level of CMI for future influenza vaccine development. The ELISPOT assay for IFN-γ is a sensitive and reproducible measure of CMI and memory immune responses and contributes to establishing requirements for the future development of vaccines against influenza, especially those used for children. PMID:18448618

Influenza Virus-Like Particles Containing M2 Induce Broadly Cross Protective Immunity

PubMed Central

Song, Jae-Min; Wang, Bao-Zhong; Park, Kyoung-Mi; Van Rooijen, Nico; Quan, Fu-Shi; Kim, Min-Chul; Jin, Hyun-Tak; Pekosz, Andrew; Compans, Richard W.; Kang, Sang-Moo

2011-01-01

Background Current influenza vaccines based on the hemagglutinin protein are strain specific and do not provide good protection against drifted viruses or emergence of new pandemic strains. An influenza vaccine that can confer cross-protection against antigenically different influenza A strains is highly desirable for improving public health. Methodology/Principal Findings To develop a cross protective vaccine, we generated influenza virus-like particles containing the highly conserved M2 protein in a membrane-anchored form (M2 VLPs), and investigated their immunogenicity and breadth of cross protection. Immunization of mice with M2 VLPs induced anti-M2 antibodies binding to virions of various strains, M2 specific T cell responses, and conferred long-lasting cross protection against heterologous and heterosubtypic influenza viruses. M2 immune sera were found to play an important role in providing cross protection against heterosubtypic virus and an antigenically distinct 2009 pandemic H1N1 virus, and depletion of dendritic and macrophage cells abolished this cross protection, providing new insight into cross-protective immune mechanisms. Conclusions/Significance These results suggest that presenting M2 on VLPs in a membrane-anchored form is a promising approach for developing broadly cross protective influenza vaccines. PMID:21267073

Variation at Extra-epitopic Amino Acid Residues Influences Suppression of Influenza Virus Replication by M158-66 Epitope-Specific CD8+ T Lymphocytes.

PubMed

van de Sandt, Carolien E; Pronk, Mark R; van Baalen, Carel A; Fouchier, Ron A M; Rimmelzwaan, Guus F

2018-06-01

Influenza virus-specific CD8 + T lymphocytes (CTLs) contribute to clearance of influenza virus infections and reduce disease severity. Variation at amino acid residues located in or outside CTL epitopes has been shown to affect viral recognition by virus-specific CTLs. In the present study, we investigated the effect of naturally occurring variation at residues outside the conserved immunodominant and HLA*0201-restricted M1 58-66 epitope, located in the influenza virus M1 protein, on the extent of virus replication in the presence of CTLs specific for the epitope. To this end, we used isogenic viruses with an M1 gene segment derived from either an avian or a human influenza virus, HLA-transgenic human epithelial cells, human T cell clones specific for the M1 58-66 epitope or a control epitope, and a novel, purposely developed in vitro system to coculture influenza virus-infected cells with T cells. We found that the M gene segment of a human influenza A/H3N2 virus afforded the virus the capacity to replicate better in the presence of M1 58-66 -specific CTLs than the M gene segment of avian viruses. These findings are in concordance with previously observed differential CTL activation, caused by variation at extra-epitopic residues, and may reflect an immune adaptation strategy of human influenza viruses that allows them to cope with potent CTL immunity to the M1 58-66 epitope in HLA-A*0201-positive individuals, resulting in increased virus replication and shedding and possibly increasing disease severity. IMPORTANCE Influenza viruses are among the leading causes of acute respiratory tract infections. CD8 + T lymphocytes display a high degree of cross-reactivity with influenza A viruses of various subtypes and are considered an important correlate of protection. Unraveling viral immune evasion strategies and identifying signs of immune adaptation are important for defining the role of CD8 + T lymphocytes in affording protection more accurately. Improving our insight into the interaction between influenza viruses and virus-specific CD8 + T lymphocyte immunity may help to advance our understanding of influenza virus epidemiology, aid in risk assessment of potentially pandemic influenza virus strains, and benefit the design of vaccines that induce more broadly protective immunity. Copyright © 2018 American Society for Microbiology.

Cutaneous immunization: an evolving paradigm in influenza vaccines

PubMed Central

Gill, Harvinder S; Kang, Sang-Moo; Quan, Fu-Shi; Compans, Richard W

2014-01-01

Introduction Most vaccines are administered by intramuscular injection using a hypodermic needle and syringe. Some limitations of this procedure include reluctance to be immunized because of fear of needlesticks, and concerns associated with the safe disposal of needles after their use. Skin delivery is an alternate route of vaccination that has potential to be painless and could even lead to dose reduction of vaccines. Recently, microneedles have emerged as a novel painless approach for delivery of influenza vaccines via the skin. Areas covered In this review, we briefly summarize the approaches and devices used for skin vaccination, and then focus on studies of skin immunization with influenza vaccines using microneedles. We discuss both the functional immune response and the nature of this immune response following vaccination with microneedles. Expert opinion The cutaneous administration of influenza vaccines using microneedles offers several advantages: it is painless, elicits stronger immune responses in preclinical studies and could improve responses in high-risk populations. These dry formulations of vaccines provide enhanced stability, a property of high importance in enabling their rapid global distribution in response to possible outbreaks of pandemic influenza and newly emerging infectious diseases. PMID:24521050

Impact of the 2004-2005 Influenza Vaccine Shortage on Immunization Practices in Long-Term Care Facilities

PubMed Central

Mody, Lona; Langa, Kenneth M.; Malani, Preeti N.

2012-01-01

Objective To assess the response of long-term care facilities (LTCFs) to the 2004-2005 influenza vaccine shortage and the impact on resident and healthcare worker (HCW) immunization rates. Methods A 12-item questionnaire was sent to 824 randomly selected LTCFs in December 2004. The following 2 open-ended questions were also asked: “How did you cope with the vaccine shortage?” and “Who helped you get your supply?” Immunization rates reported by LTCF administrators for 2003-2003 and 2003-2004 were compared with those for 2004-2005. Immunization rates were defined as the proportion of all eligible residents and HCWs who received influenza vaccine. Results Responses were received from 380 LTCFs (46.3%), which had a total of 38,447 beds. Resident mean influenza immunization rates (±SD) decreased from 85% ± 15.3% in 2002-2003 and 85.1% ± 15.3% in 2003-2004 to 81.9% ± 19.4% in the 2004-2005 influenza season (P = .025). The immunization rates among HCWs also decreased from 51% in 2002-2003 and 2003-2004 to 38.4% in 2004-2005 (P < .001). In response to one of the open-ended questions, 96 facilities (25.3%) reported that they obtained vaccine from 2 or more sources. Eight percent commented on specific intensified infection control efforts, and only 2.3% commented on emergency preparedness. Conclusions The influenza vaccine shortage in 2004-2005 impacted immunization practices of LTCFs across the United States, leading to decreases in both resident and HCW vaccination rates. The significant decrease in vaccination rates in LTCFs is of concern and has broad implications for policy makers working on emergency preparedness for a possible pandemic of influenza. PMID:16622817

Dietary supplementation with lacto-wolfberry enhances the immune response and reduces pathogenesis to influenza infection in mice

USDA-ARS?s Scientific Manuscript database

Despite the availability of vaccines, influenza is a significant public health problem, emphasizing the need for development of additional strategies to enhance host defense against influenza. Wolfberry or Goji berry, long used as a medicinal food in China, has recently been shown to improve immune ...

A Live Attenuated Influenza A(H5N1) Vaccine Induces Long-Term Immunity in the Absence of a Primary Antibody Response

PubMed Central

Talaat, Kawsar R.; Luke, Catherine J.; Khurana, Surender; Manischewitz, Jody; King, Lisa R.; McMahon, Bridget A.; Karron, Ruth A.; Lewis, Kristen D. C.; Qin, Jing; Follmann, Dean A.; Golding, Hana; Neuzil, Kathleen M.; Subbarao, Kanta

2014-01-01

Background. Highly pathogenic avian influenza A(H5N1) causes severe infections in humans. We generated 2 influenza A(H5N1) live attenuated influenza vaccines for pandemic use (pLAIVs), but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long-lasting immunity that could be detected by administration of inactivated subvirion influenza A(H5N1) vaccine (ISIV). Methods. The following groups were invited to participate in the study: persons who previously received influenza A(H5N1) pLAIV; persons who previously received an irrelevant influenza A(H7N3) pLAIV; and community members who were naive to influenza A(H5N1) and LAIV. LAIV-experienced subjects received a single 45-μg dose of influenza A(H5N1) ISIV. Influenza A(H5N1)– and LAIV-naive subjects received either 1 or 2 doses of ISIV. Results. In subjects who had previously received antigenically matched influenza A(H5N1) pLAIV followed by 1 dose of ISIV compared with those who were naive to influenza A(H5N1) and LAIV and received 2 doses of ISIV, we observed an increased frequency of antibody response (82% vs 50%, by the hemagglutination inhibition assay) and a significantly higher antibody titer (112 vs 76; P = .04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in influenza A(H5N1) pLAIV–primed subjects. Conclusions. ISIV administration unmasked long-lasting immunity in influenza A(H5N1) pLAIV recipients, with a rapid, high-titer, high-quality antibody response that was broadly cross-reactive across several influenza A(H5N1) clades. Clinical Trials Registration. NCT01109329. PMID:24604819

Summary of the NACI Statement on Seasonal Influenza Vaccine for 2017-2018.

PubMed

Vaudry, W; Stirling, R

2017-05-04

Influenza is a respiratory infection caused primarily by influenza A and B viruses. Vaccination is the most effective way to prevent influenza and its complications. The National Advisory Committee on Immunization (NACI) provides recommendations regarding seasonal influenza vaccines annually to the Public Health Agency of Canada (PHAC). To summarize the NACI recommendations regarding the use of seasonal influenza vaccines for the 2017-2018 influenza season. Annual influenza vaccine recommendations are developed by NACI's Influenza Working Group for consideration and approval by NACI, based on NACI's evidence-based process for developing recommendations. The recommendations include a consideration of the burden of influenza illness and the target populations for vaccination; efficacy and effectiveness, immunogenicity and safety of influenza vaccines; vaccine schedules; and other aspects of influenza immunization. These recommendations are published annually on the Agency's website in the NACI Advisory Committee Statement: Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine (the Statement). The annual statement has been updated for the 2017-2018 influenza season to incorporate recommendations for the use of live attenuated influenza vaccine (LAIV) that were contained in two addenda published after the 2016-2017 statement. These recommendations were 1) that egg-allergic individuals may be vaccinated against influenza using the low ovalbumin-containing LAIV licensed for use in Canada and 2) to continue to recommend the use of LAIV in children and adolescents 2-17 years of age, but to remove the preferential recommendation for its use. NACI continues to recommend annual influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk, and others as indicated.

Galvanizing medical students in the administration of influenza vaccines: the Stanford Flu Crew

PubMed Central

Rizal, Rachel E; Mediratta, Rishi P; Xie, James; Kambhampati, Swetha; Hills-Evans, Kelsey; Montacute, Tamara; Zhang, Michael; Zaw, Catherine; He, Jimmy; Sanchez, Magali; Pischel, Lauren

2015-01-01

Many national organizations call for medical students to receive more public health education in medical school. Nonetheless, limited evidence exists about successful servicelearning programs that administer preventive health services in nonclinical settings. The Flu Crew program, started in 2001 at the Stanford University School of Medicine, provides preclinical medical students with opportunities to administer influenza immunizations in the local community. Medical students consider Flu Crew to be an important part of their medical education that cannot be learned in the classroom. Through delivering vaccines to where people live, eat, work, and pray, Flu Crew teaches medical students about patient care, preventive medicine, and population health needs. Additionally, Flu Crew allows students to work with several partners in the community in order to understand how various stakeholders improve the delivery of population health services. Flu Crew teaches students how to address common vaccination myths and provides insights into implementing public health interventions. This article describes the Stanford Flu Crew curriculum, outlines the planning needed to organize immunization events, shares findings from medical students’ attitudes about population health, highlights the program’s outcomes, and summarizes the lessons learned. This article suggests that Flu Crew is an example of one viable service-learning modality that supports influenza vaccinations in nonclinical settings while simultaneously benefiting future clinicians. PMID:26170731

The impact of an immunization check-up at a pharmacist-provided employee health screening.

PubMed

Sparkman, Amy; Brookhart, Andrea L; Goode, Jean-Venable Kelly R

To determine which types of vaccine recommendations were accepted and acted upon by patients after an immunization check-up at a pharmacist-provided employee health screening, and to evaluate if there was a difference between influenza and non-influenza vaccines. Retrospective, observational. Supermarket chain. Employees and covered spouses. Immunization check-up. Acceptance rate of immunization recommendation. This retrospective observational study evaluated the impact of an immunization check-up in individuals who participated in one of the 252 pharmacist-provided health screenings in central Virginia in 2015. All employee health screenings were completed from July 1, 2015, to September 30, 2015. Because immunization status was assessed 6 months after each person received his or her health screening, data were collected from January 1, 2016, to March 30, 2016, and analyzed to collect the number and type of vaccines recommended during the immunization check-up. Each eligible participant's profile was evaluated to determine if he or she received the vaccines at any Kroger pharmacy within 6 months. Patient identifiers were not collected; however, demographics including age, relevant disease state history, and smoking status were collected with immunization recommendations and uptake. Data were analyzed with the use of descriptive statistics. A total of 349 immunization recommendations were made, including 248 influenza; 42 pneumococcal polysaccharide (PPSV23); 40 tetanus, diphtheria, and pertussis (Tdap); 12 herpes zoster; 4 pneumococcal conjugate (PCV13); and 3 hepatitis B. Both influenza and PCV13 had acceptance rates of 50%, and herpes zoster, Tdap, hepatitis B, and PPSV23 had 42%, 35%, 33%, and 24% acceptance rates, respectively. Influenza recommendations had a 50% acceptance rate compared with a 32% acceptance rate of non-influenza recommendations (P = 0.002). An immunization check-up performed at a pharmacist-provided employee health screening can lead to patient acceptance of recommendations and receipt of needed immunizations. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Long-Term Immunogenicity of an Inactivated Split-Virion 2009 Pandemic Influenza A H1N1 Virus Vaccine with or without Aluminum Adjuvant in Mice

PubMed Central

Xu, Wenting; Zheng, Mei; Zhou, Feng

2015-01-01

In 2009, a global epidemic of influenza A(H1N1) virus caused the death of tens of thousands of people. Vaccination is the most effective means of controlling an epidemic of influenza and reducing the mortality rate. In this study, the long-term immunogenicity of influenza A/California/7/2009 (H1N1) split vaccine was observed as long as 15 months (450 days) after immunization in a mouse model. Female BALB/c mice were immunized intraperitoneally with different doses of aluminum-adjuvanted vaccine. The mice were challenged with a lethal dose (10× 50% lethal dose [LD50]) of homologous virus 450 days after immunization. The results showed that the supplemented aluminum adjuvant not only effectively enhanced the protective effect of the vaccine but also reduced the immunizing dose of the vaccine. In addition, the aluminum adjuvant enhanced the IgG antibody level of mice immunized with the H1N1 split vaccine. The IgG level was correlated to the survival rate of the mice. Aluminum-adjuvanted inactivated split-virion 2009 pandemic influenza A H1N1 vaccine has good immunogenicity and provided long-term protection against lethal influenza virus challenge in mice. PMID:25589552

Marketing paediatric influenza vaccination: results of a major metropolitan trial

PubMed Central

Van Buynder, Paul G.; Carcione, Dale; Rettura, Vince; Daly, Alison; Woods, Emily

2010-01-01

Please cite this paper as: Van Buynder et al. (2010) Marketing paediatric influenza vaccination: results of a major metropolitan trial. Influenza and Other Respiratory Viruses 5(1), 33–38. Objectives  After a cluster of rapidly fulminant influenza related toddler deaths in a Western Australian metropolis, children aged six to 59 months were offered influenza vaccination in subsequent winters. Some parental resistance was expected and previous poor uptake of paediatric influenza vaccination overseas was noted. A marketing campaign addressing barriers to immunization was developed to maximise uptake. Design  Advertising occurred in major statewide newspapers, via public poster displays and static ‘eye‐lite’ displays, via press releases, via a series of rolling radio advertisements, via direct marketing to child care centres, and via a linked series of web‐sites. Parents were subsequently surveyed to assess reasons for vaccination. Main Outcome Results  The campaign produced influenza vaccination coverage above that previously described elsewhere and led to a proportionate reduction in influenza notifications in this age group compared to previous seasons. Conclusions  Influenza in children comes with significant morbidity and some mortality. Paediatric influenza vaccination is safe, well tolerated and effective if two doses are given. A targeted media campaign can increase vaccine uptake if it reinforces the seriousness of influenza and addresses community ‘myths’ about influenza and influenza vaccine. The lessons learned enabling enhancements of similar programs elsewhere. PMID:21138538

Protecting patients, protecting healthcare workers: a review of the role of influenza vaccination

PubMed Central

Music, T

2012-01-01

MUSIC T. (2012) A review of the role the role of influenza vaccination in protecting patients, protecting healthcare workers the role of influenza vaccination. International Nursing Review59, 161–167 Aim: Many health authorities recommend routine influenza vaccination for healthcare workers (HCWs), and during the 2009 A (H1N1) pandemic, the World Health Organization (WHO) recommended immunization of all HCWs worldwide. As this remains an important area of policy debate, this paper examines the case for vaccination, the role of local guidelines, barriers to immunization and initiatives to increase uptake. Background: Seasonal influenza is a major threat to public health, causing up to 1 million deaths annually. Extensive evidence supports the vaccination of priority groups, including HCWs. Immunization protects HCWs themselves, and their vulnerable patients from nosocomial influenza infections. In addition, influenza can disrupt health services and impact healthcare organizations financially. Immunization can reduce staff absences, offer cost savings and provide economic benefits. Methods: This paper reviews official immunization recommendations and HCW vaccination studies, including a recent International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) survey of 26 countries from each region of the world. Results: HCW immunization is widely recommended and supported by the WHO. In the IFPMA study, 88% of countries recommended HCW vaccination, and 61% supported this financially (with no correlation to country development status). Overall, coverage can be improved, and research shows that uptake may be impacted by lack of conveniently available vaccines and misconceptions regarding vaccine safety/efficacy and influenza risk. Conclusions: Many countries recommend HCW vaccination against influenza. In recent years, there has been an increased uptake rate among HCWs in some countries, but not in others. Several initiatives can increase coverage, including education, easy access to free vaccines and the use of formal declination forms. The case for HCW vaccination is clear, and in an effort to further accelerate uptake as a patient safety measure, an increasing number of healthcare organizations, particularly in the USA, are implementing mandatory immunization policies, similar to other obligatory hygiene measures. However, it would be desirable if similar high vaccination uptake rates could be achieved through voluntary procedures. PMID:22591085

Verifying influenza and pneumococcal immunization status of children in 2009-2010 from primary care practice records and from the North Carolina Immunization Registry.

PubMed

Poehling, Katherine A; Vannoy, Lauren; Peters, Timothy R

2013-01-01

The North Carolina Immunization Registry (NCIR) has been available since 2004. We sought to measure its utilization among practices that provide primary care for children who are enrolled in a prospective influenza surveillance study. This study included children aged 0.5-17 years who presented with fever or acute respiratory symptoms to an emergency department or inpatient setting in Winston-Salem, North Carolina, from September 1, 2009, through May 19, 2010. Study team members verified influenza and pneumococcal immunization status by requesting records from each child's primary care practice and by independently reviewing the NCIR. We assessed agreement of nonregistry immunization medical records with NCIR data using the kappa statistic. Fifty-six practices confirmed the immunization status of 292 study-enrolled children. For most children (238/292, 82%), practices verified the child's immunizations by providing a copy of the NCIR record. For 54 children whose practices verified their immunizations by providing practice records alone, agreement with the NCIR by the kappa statistic was 0.6-0.7 for seasonal and monovalent H1N1 influenza vaccines and 0.8-0.9 for pneumococcal conjugate and polysaccharide vaccines. A total of 221 (98%) of 226 enrolled children younger than 6 years of age had 2 or more immunizations documented in the NCIR. NCIR usage may vary in other regions of North Carolina. More than 95% of children younger than 6 years of age had 2 or more immunizations documented in the NCIR; thus, the Centers for Disease Control and Prevention 2010 goal for immunization information systems was met in this population. We found substantial agreement between practice records and the NCIR for influenza and pneumococcal immunizations in children.

Championing School-Located Influenza Immunization: The School Nurse's Role

ERIC Educational Resources Information Center

Li, Christina; Freedman, Marian; Boyer-Chu, Lynda

2009-01-01

According to the 2008 recommendations of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, influenza vaccine should be administered on an annual basis to all children aged 6 months through 18 years. School-age children are more likely than any other age group to be infected with influenza, and…

Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus

PubMed Central

Morgan, Sophie B.; Hemmink, Johanneke D.; Porter, Emily; Harley, Ross; Shelton, Holly; Aramouni, Mario; Everett, Helen E.; Brookes, Sharon M.; Bailey, Michael; Townsend, Alain M.; Charleston, Bryan

2016-01-01

Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. PMID:27183611

Protective Immunity and Safety of a Genetically Modified Influenza Virus Vaccine

PubMed Central

Garcia, Cristiana Couto; Filho, Bruno Galvão; Gonçalves, Ana Paula de Faria; Lima, Braulio Henrique Freire; Lopes, Gabriel Augusto Oliveira; Rachid, Milene Alvarenga; Peixoto, Andiara Cristina Cardoso; de Oliveira, Danilo Bretas; Ataíde, Marco Antônio; Zirke, Carla Aparecida; Cotrim, Tatiane Marques; Costa, Érica Azevedo; Almeida, Gabriel Magno de Freitas; Russo, Remo Castro; Gazzinelli, Ricardo Tostes; Machado, Alexandre de Magalhães Vieira

2014-01-01

Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens. PMID:24927156

Positive Network Assortativity of Influenza Vaccination at a High School: Implications for Outbreak Risk and Herd Immunity

PubMed Central

He, Jianping; Cao, Guohong; Rainey, Jeanette J.; Gao, Hongjiang; Uzicanin, Amra; Salathé, Marcel

2014-01-01

Schools are known to play a significant role in the spread of influenza. High vaccination coverage can reduce infectious disease spread within schools and the wider community through vaccine-induced immunity in vaccinated individuals and through the indirect effects afforded by herd immunity. In general, herd immunity is greatest when vaccination coverage is highest, but clusters of unvaccinated individuals can reduce herd immunity. Here, we empirically assess the extent of such clustering by measuring whether vaccinated individuals are randomly distributed or demonstrate positive assortativity across a United States high school contact network. Using computational models based on these empirical measurements, we further assess the impact of assortativity on influenza disease dynamics. We found that the contact network was positively assortative with respect to influenza vaccination: unvaccinated individuals tended to be in contact more often with other unvaccinated individuals than with vaccinated individuals, and these effects were most pronounced when we analyzed contact data collected over multiple days. Of note, unvaccinated males contributed substantially more than unvaccinated females towards the measured positive vaccination assortativity. Influenza simulation models using a positively assortative network resulted in larger average outbreak size, and outbreaks were more likely, compared to an otherwise identical network where vaccinated individuals were not clustered. These findings highlight the importance of understanding and addressing heterogeneities in seasonal influenza vaccine uptake for prevention of large, protracted school-based outbreaks of influenza, in addition to continued efforts to increase overall vaccine coverage. PMID:24505274

Impact of age and pre-existing influenza immune responses in humans receiving split inactivated influenza vaccine on the induction of the breadth of antibodies to influenza A strains

PubMed Central

Nuñez, Ivette A.; Carlock, Michael A.; Allen, James D.; Owino, Simon O.; Moehling, Krissy K.; Nowalk, Patricia; Susick, Michael; Diagle, Kensington; Sweeney, Kristen; Mundle, Sophia; Vogel, Thorsten U.; Delagrave, Simon; Ramgopal, Moti; Zimmerman, Richard K.; Kleanthous, Harry

2017-01-01

Most humans have pre-existing immunity to influenza viruses. In this study, volunteers (ages of 18–85 years) were vaccinated with split, inactivated Fluzone™ influenza vaccine in four consecutive influenza seasons from 2013 to 2016 seasons. The impact of repeated vaccination on breadth and durability of antibodies was assessed as a result of vaccine strain changes. Total IgG anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity increased in all age groups against both influenza A HA components in the vaccine post-vaccination (day 21). However, younger subjects maintained seroprotective titers to the vaccine strains, which resulted in higher seroconversion rates in the elderly, since the HAI titers in elderly subjects were more likely to decline prior to the next season. Young subjects had significant HAI activity against historical, as well as contemporary H1 and H3 vaccine strains from the mid-1980s to present. In contrast, elderly subjects had HAI activity to H1 strains from all years, but were more likely to have HAI activity to older strains from 1918-1950s. They also had a more restricted HAI profile against H3 viruses compared to young subjects recognizing H3N2 influenza viruses from the mid-2000s to present. Vaccine recipients were then categorized by whether subjects seroconverted from a seronegative or seropositive pre-vaccination state. Regardless of age, immunological recall or ‘back-boosting’ to antigenically related strains were associated with seroconversion to the vaccine strain. Overall, both younger and older people have the ability to mount a breadth of immune responses following influenza vaccination. This report describes how imprinting exposure differs across age groups, influences antibody cross-reactivity to past hemagglutinin antigenic variants, and shapes immune responses elicited by current split inactivated influenza vaccines. Understanding how current influenza vaccines are influenced by pre-existing immunity in people of different ages is critical for designing the next-generation of ‘universal’ or broadly-protective influenza vaccines. PMID:29091724

Surveillance of influenza vaccination coverage--United States, 2007-08 through 2011-12 influenza seasons.

PubMed

Lu, Peng-jun; Santibanez, Tammy A; Williams, Walter W; Zhang, Jun; Ding, Helen; Bryan, Leah; O'Halloran, Alissa; Greby, Stacie M; Bridges, Carolyn B; Graitcer, Samuel B; Kennedy, Erin D; Lindley, Megan C; Ahluwalia, Indu B; LaVail, Katherine; Pabst, Laura J; Harris, LaTreace; Vogt, Tara; Town, Machell; Singleton, James A

2013-10-25

Substantial improvement in annual influenza vaccination of recommended groups is needed to reduce the health effects of influenza and reach Healthy People 2020 targets. No single data source provides season-specific estimates of influenza vaccination coverage and related information on place of influenza vaccination and concerns related to influenza and influenza vaccination. 2007-08 through 2011-12 influenza seasons. CDC uses multiple data sources to obtain estimates of vaccination coverage and related data that can guide program and policy decisions to improve coverage. These data sources include the National Health Interview Survey (NHIS), the Behavioral Risk Factor Surveillance System (BRFSS), the National Flu Survey (NFS), the National Immunization Survey (NIS), the Immunization Information Systems (IIS) eight sentinel sites, Internet panel surveys of health-care personnel and pregnant women, and the Pregnancy Risk Assessment and Monitoring System (PRAMS). National influenza vaccination coverage among children aged 6 months-17 years increased from 31.1% during 2007-08 to 56.7% during the 2011-12 influenza season as measured by NHIS. Vaccination coverage among children aged 6 months-17 years varied by state as measured by NIS. Changes from season to season differed as measured by NIS and NHIS. According to IIS sentinel site data, full vaccination (having either one or two seasonal influenza vaccinations, as recommended by the Advisory Committee on Immunization Practices for each influenza season, based on the child's influenza vaccination history) with up to two recommended doses for the 2011-12 season was 27.1% among children aged 6 months-8 years and was 44.3% for the youngest children (aged 6-23 months). Influenza vaccination coverage among adults aged ≥18 years increased from 33.0% during 2007-08 to 38.3% during the 2011-12 influenza season as measured by NHIS. Vaccination coverage by age group for the 2011-12 season as measured by BRFSS was <5 percentage points different from NHIS estimates, whereas NFS estimates were 6-8 percentage points higher than BRFSS estimates. Vaccination coverage among persons aged ≥18 years varied by state as measured by BRFSS. For adults aged ≥18 years, a doctor's office was the most common place for receipt of influenza vaccination (38.4%, BRFSS; 32.5%, NFS) followed by a pharmacy (20.1%, BRFSS; 19.7%, NFS). Overall, 66.9% of health-care personnel (HCP) reported having been vaccinated during the 2011-12 season, as measured by an Internet panel survey of HCP, compared with 62.4%, as estimated through NHIS. Vaccination coverage among pregnant women was 47.0%, as measured by an Internet panel survey of women pregnant during the influenza season, and 43.0%, as measured by BRFSS during the 2011-12 influenza season. Overall, as measured by NFS, 86.8% of adults aged ≥18 years rated the influenza vaccine as very or somewhat effective, and 46.5% of adults aged ≥18 years believed their risk for getting sick with influenza if unvaccinated was high or somewhat high. During the 2011-12 season, influenza vaccination coverage varied by state, age group, and selected populations (e.g., HCP and pregnant women), with coverage estimates well below the Healthy People 2020 goal of 70% for children aged 6 months-17 years, 70% for adults aged ≥18 years, and 90% for HCP. Continued efforts are needed to encourage health-care providers to offer influenza vaccination and to promote public health education efforts among various populations to improve vaccination coverage. Ongoing surveillance to obtain coverage estimates and information regarding other issues related to influenza vaccination (e.g., knowledge, attitudes, and beliefs) is needed to guide program and policy improvements to reduce morbidity and mortality associated with influenza by increasing vaccination rates. Ongoing comparisons of telephone and Internet panel surveys with in-person surveys such as NHIS are needed for appropriate interpretation of data and resulting public health actions. Examination of results from all data sources is necessary to fully assess the various components of influenza vaccination coverage among different populations in the United States.

Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1) virus infection during pregnancy

PubMed Central

Dembinski, Jennifer L.; Laake, Ida; Hungnes, Olav; Cox, Rebecca; Oftung, Fredrik; Trogstad, Lill; Mjaaland, Siri

2017-01-01

Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI) responses in pandemic influenza A(H1N1)pdm09 (pdm09) virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu). The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC). Infected cases (N = 75) were defined by having a serum hemagglutination inhibition (HI) titer > = 20 to influenza pdm09 virus at the time of delivery, while controls (N = 75) were randomly selected among non-infected pregnant women (HI titer <10). In ELISpot assays cases had higher frequencies of IFNγ+ CD8+ T cells responding to pdm09 virus or conserved CD8 T cell-restricted influenza A virus epitopes, compared to controls. Within this T cell population, frequencies of CD95+ late effector (CD45RA+CCR7-) and naive (CD45RA+CCR7+) CD8+ memory T cells correlated inversely with self-reported influenza illness (ILI) symptoms. ILI symptoms in infected women were also associated with lower numbers of poly-functional (IFNγ+TNFα+, IL2+IFNγ+, IL2+IFNγ+TNFα+) CD4+ T cells and increased frequencies of IFNγ+CD3-CD7+ NK cells compared to asymptomatic cases, or controls, after stimulation with the pdm09 virus. Taken together, virus specific and functionally distinct T and NK cell populations may serve as cellular immune correlates of clinical outcomes of pandemic influenza disease in pregnant women. Our results may provide information important for future universal influenza vaccine design. PMID:29145441

Distinct T and NK cell populations may serve as immune correlates of protection against symptomatic pandemic influenza A(H1N1) virus infection during pregnancy.

PubMed

Savic, Miloje; Dembinski, Jennifer L; Laake, Ida; Hungnes, Olav; Cox, Rebecca; Oftung, Fredrik; Trogstad, Lill; Mjaaland, Siri

2017-01-01

Maternal influenza infection during pregnancy is associated with increased risk of morbidity and mortality. However, the link between the anti-influenza immune responses and health-related risks during infection is not well understood. We have analyzed memory T and NK cell mediated immunity (CMI) responses in pandemic influenza A(H1N1)pdm09 (pdm09) virus infected non-vaccinated pregnant women participating in the Norwegian Influenza Pregnancy Cohort (NorFlu). The cohort includes information on immunization, self-reported health and disease status, and biological samples (plasma and PBMC). Infected cases (N = 75) were defined by having a serum hemagglutination inhibition (HI) titer > = 20 to influenza pdm09 virus at the time of delivery, while controls (N = 75) were randomly selected among non-infected pregnant women (HI titer <10). In ELISpot assays cases had higher frequencies of IFNγ+ CD8+ T cells responding to pdm09 virus or conserved CD8 T cell-restricted influenza A virus epitopes, compared to controls. Within this T cell population, frequencies of CD95+ late effector (CD45RA+CCR7-) and naive (CD45RA+CCR7+) CD8+ memory T cells correlated inversely with self-reported influenza illness (ILI) symptoms. ILI symptoms in infected women were also associated with lower numbers of poly-functional (IFNγ+TNFα+, IL2+IFNγ+, IL2+IFNγ+TNFα+) CD4+ T cells and increased frequencies of IFNγ+CD3-CD7+ NK cells compared to asymptomatic cases, or controls, after stimulation with the pdm09 virus. Taken together, virus specific and functionally distinct T and NK cell populations may serve as cellular immune correlates of clinical outcomes of pandemic influenza disease in pregnant women. Our results may provide information important for future universal influenza vaccine design.

An Assessment of the Expected Cost-Effectiveness of Quadrivalent Influenza Vaccines in Ontario, Canada Using a Static Model.

PubMed

Chit, Ayman; Roiz, Julie; Aballea, Samuel

2015-01-01

Ontario, Canada, immunizes against influenza using a trivalent inactivated influenza vaccine (IIV3) under a Universal Influenza Immunization Program (UIIP). The UIIP offers IIV3 free-of-charge to all Ontarians over 6 months of age. A newly approved quadrivalent inactivated influenza vaccine (IIV4) offers wider protection against influenza B disease. We explored the expected cost-utility and budget impact of replacing IIV3 with IIV4, within the context of Ontario's UIIP, using a probabilistic and static cost-utility model. Wherever possible, epidemiological and cost data were obtained from Ontario sources. Canadian or U.S. sources were used when Ontario data were not available. Vaccine efficacy for IIV3 was obtained from the literature. IIV4 efficacy was derived from meta-analysis of strain-specific vaccine efficacy. Conservatively, herd protection was not considered. In the base case, we used IIV3 and IIV4 prices of $5.5/dose and $7/dose, respectively. We conducted a sensitivity analysis on the price of IIV4, as well as standard univariate and multivariate statistical uncertainty analyses. Over a typical influenza season, relative to IIV3, IIV4 is expected to avert an additional 2,516 influenza cases, 1,683 influenza-associated medical visits, 27 influenza-associated hospitalizations, and 5 influenza-associated deaths. From a societal perspective, IIV4 would generate 76 more Quality Adjusted Life Years (QALYs) and a net societal budget impact of $4,784,112. The incremental cost effectiveness ratio for this comparison was $63,773/QALY. IIV4 remains cost-effective up to a 53% price premium over IIV3. A probabilistic sensitivity analysis showed that IIV4 was cost-effective with a probability of 65% for a threshold of $100,000/QALY gained. IIV4 is expected to achieve reductions in influenza-related morbidity and mortality compared to IIV3. Despite not accounting for herd protection, IIV4 is still expected to be a cost-effective alternative to IIV3 up to a price premium of 53%. Our conclusions were robust in the face of sensitivity analyses.

Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza.

PubMed

Wang, Jiong; Hilchey, Shannon P; Hyrien, Ollivier; Huertas, Nelson; Perry, Sheldon; Ramanunninair, Manojkumar; Bucher, Doris; Zand, Martin S

2015-01-01

The human immune response to influenza vaccination depends in part on preexisting cross-reactive (heterosubtypic) immunity from previous infection by, and/or vaccination with, influenza strains that share antigenic determinants with the vaccine strains. However, current methods for assessing heterosubtypic antibody responses against influenza, including the hemagglutination-inhibition (HAI) assay and ELISA, are time and labor intensive, and require moderate amounts of serum and reagents. To address these issues we have developed a fluorescent multiplex assay, mPlex-Flu, that rapidly and simultaneously measures strain specific IgG, IgA, and IgM antibodies against influenza hemagglutinin (HA) from multiple viral strains. We cloned, expressed and purified HA proteins from 12 influenza strains, and coupled them to multiplex beads. Assay validation showed that minimal sample volumes (<5 μl of serum) were needed, and the assay had a linear response over a four Log10 range. The assay detected nanogram levels of anti-influenza specific antibodies, had high accuracy and reproducibility, with an average percentage coefficient of variation (%CV) of 9.06 for intra-assay and 12.94 for inter-assay variability. Pre- and post-intramuscular trivalent influenza vaccination levels of virus specific Ig were consistent with HAI titer and ELISA measurements. A significant advantage of the mPLEX-Flu assay over the HAI assay is the ability to perform antigenic cartography, determining the antigenic distances between influenza HA's, without mathematical correction for HAI data issues. For validation we performed antigenic cartography on 14 different post-influenza infection ferret sera assayed against 12 different influenza HA's. Results were in good agreement with a phylogenetic tree generated from hierarchical clustering of the genomic HA sequences. This is the first report of the use of a multiplex method for antigenic cartography using ferret sera. Overall, the mPlex-Flu assay provides a powerful tool to rapidly assess the influenza antibody repertoire in large populations and to study heterosubtypic immunity induced by influenza vaccination.

Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza

PubMed Central

Wang, Jiong; Hilchey, Shannon P.; Hyrien, Ollivier; Huertas, Nelson; Perry, Sheldon; Ramanunninair, Manojkumar; Bucher, Doris; Zand, Martin S.

2015-01-01

The human immune response to influenza vaccination depends in part on preexisting cross-reactive (heterosubtypic) immunity from previous infection by, and/or vaccination with, influenza strains that share antigenic determinants with the vaccine strains. However, current methods for assessing heterosubtypic antibody responses against influenza, including the hemagglutination-inhibition (HAI) assay and ELISA, are time and labor intensive, and require moderate amounts of serum and reagents. To address these issues we have developed a fluorescent multiplex assay, mPlex-Flu, that rapidly and simultaneously measures strain specific IgG, IgA, and IgM antibodies against influenza hemagglutinin (HA) from multiple viral strains. We cloned, expressed and purified HA proteins from 12 influenza strains, and coupled them to multiplex beads. Assay validation showed that minimal sample volumes (<5 μl of serum) were needed, and the assay had a linear response over a four Log10 range. The assay detected nanogram levels of anti-influenza specific antibodies, had high accuracy and reproducibility, with an average percentage coefficient of variation (%CV) of 9.06 for intra-assay and 12.94 for inter-assay variability. Pre- and post-intramuscular trivalent influenza vaccination levels of virus specific Ig were consistent with HAI titer and ELISA measurements. A significant advantage of the mPLEX-Flu assay over the HAI assay is the ability to perform antigenic cartography, determining the antigenic distances between influenza HA’s, without mathematical correction for HAI data issues. For validation we performed antigenic cartography on 14 different post-influenza infection ferret sera assayed against 12 different influenza HA’s. Results were in good agreement with a phylogenetic tree generated from hierarchical clustering of the genomic HA sequences. This is the first report of the use of a multiplex method for antigenic cartography using ferret sera. Overall, the mPlex-Flu assay provides a powerful tool to rapidly assess the influenza antibody repertoire in large populations and to study heterosubtypic immunity induced by influenza vaccination. PMID:26103163

Developing Universal Influenza Vaccines: Hitting the Nail, Not Just on the Head

PubMed Central

Wiersma, Lidewij C. M.; Rimmelzwaan, Guus F.; de Vries, Rory D.

2015-01-01

Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines. PMID:26343187

Increasing immunization: a Medicaid managed care model.

PubMed

Browngoehl, K; Kennedy, K; Krotki, K; Mainzer, H

1997-01-01

To evaluate the impact of an immunization outreach program on immunization rates. A Pennsylvania independent practice association model managed care organization (100% Medicaid). Retrospective cohort study (N = 2511) of children 30 to 35 months of age from two age cohorts that compared immunization rates for Advisory Committee on Immunization Practices schedules for diphtheria-tetanus-pertussis, oral polio vaccine, measles-mumps-rubella, and Haemophilus influenza type b. An evaluation of the outreach component of the program compared treatment and nontreatment subgroups of one age cohort (N = 1002). The immunization program targeted approximately 19 000 members from birth to 6 years of age. The program components included computerized tracking and reminders, member and provider education, provider incentives, member incentives, and home visiting outreach. Data indicate that the treatment group has higher completed immunization rates at 35 months of age than does the control group. Furthermore, data show that members with home visits have significantly higher completed immunization rates than do other members. The corresponding comparisons for age-appropriate immunizations by 24 months indicate a nonsignificant trend of increased rates. The data provide evidence supporting a correlation between comprehensive strategies (computerized tracking, member and provider education and incentives, and home visiting) and increased immunization rates. Those individuals who received home visits were more likely to complete an immunization series by 35 months of age than those who did not. However, within the Mercy Health Plan program, age-appropriate immunizations are not significantly affected by home-visiting outreach.

Deaths averted by influenza vaccination in the U.S. during the seasons 2005/06 through 2013/14.

PubMed

Foppa, Ivo M; Cheng, Po-Yung; Reynolds, Sue B; Shay, David K; Carias, Cristina; Bresee, Joseph S; Kim, Inkyu K; Gambhir, Manoj; Fry, Alicia M

2015-06-12

Excess mortality due to seasonal influenza is substantial, yet quantitative estimates of the benefit of annual vaccination programs on influenza-associated mortality are lacking. We estimated the numbers of deaths averted by vaccination in four age groups (0.5 to 4, 5 to 19, 20 to 64 and ≥65 yrs.) for the nine influenza seasons from 2005/6 through 2013/14. These estimates were obtained using a Monte Carlo approach applied to weekly U.S. age group-specific estimates of influenza-associated excess mortality, monthly vaccination coverage estimates and summary seasonal influenza vaccine effectiveness estimates to obtain estimates of the number of deaths averted by vaccination. The estimates are conservative as they do not include indirect vaccination effects. From August, 2005 through June, 2014, we estimated that 40,127 (95% confidence interval [CI] 25,694 to 59,210) deaths were averted by influenza vaccination. We found that of all studied seasons the most deaths were averted by influenza vaccination during the 2012/13 season (9398; 95% CI 2,386 to 19,897) and the fewest during the 2009/10 pandemic (222; 95% CI 79 to 347). Of all influenza-associated deaths averted, 88.9% (95% CI 83 to 92.5%) were in people ≥65 yrs. old. The estimated number of deaths averted by the US annual influenza vaccination program is considerable, especially among elderly adults and even when vaccine effectiveness is modest, such as in the 2012/13 season. As indirect effects ("herd immunity") of vaccination are ignored, these estimates represent lower bound estimates and are thus conservative given valid excess mortality estimates. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dependence of the results of ecological-epidemic investigation of influenza A(H1N1) on immunity

NASA Astrophysics Data System (ADS)

Fathudinova, Mohinav; Alimova, Barno; Rahimova, Halima

2016-07-01

This report presents the results of ecology-epidemical and immunological researches influ-enza virus A (H1 N1) and acute respiratory infection in Dushanbe from 2011 till 2015. The received results epidemiological and immunological analysis showed us, that last years has been changed not only characteristics of influenza epidemic, but it can not be notice the low-er of intensively of the collective immunity to actual versions influenza viruses A and B

Cross-protective immunity against influenza A/H1N1 virus challenge in mice immunized with recombinant vaccine expressing HA gene of influenza A/H5N1 virus

PubMed Central

2013-01-01

Background Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. Method In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. Results In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. Conclusion After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can be enhanced by IL-2 as an adjuvant. Cellular immune responses may play an important role in HSI against influenza virus. PMID:24053449

Severe pediatric influenza in California, 2003-2005: implications for immunization recommendations.

PubMed

Louie, Janice K; Schechter, Robert; Honarmand, Somayeh; Guevara, Hugo F; Shoemaker, Trevor R; Madrigal, Nora Y; Woodfill, Celia J I; Backer, Howard D; Glaser, Carol A

2006-04-01

The 2003-2004 influenza season was marked by both the emergence of a new drift "Fujian" strain of influenza A virus and prominent reports of increased influenza-related deaths in children in the absence of baseline data for comparison. In December 2003, the California Department of Health Services initiated surveillance of children who were hospitalized in California with severe influenza in an attempt to measure its impact and to identify additional preventive measures. From December 2003 to May 2005, surveillance of children who were hospitalized in PICUs or dying in the hospital with laboratory evidence of influenza was performed by hospital infection control practitioners and local public health departments using a standardized case definition and reporting form. In the 2003-2004 and 2004-2005 influenza seasons, 125 and 35 cases, respectively, of severe influenza in children were identified in California. The mean and median age of cases were 3.1 years and 1.5 years, with breakdown as follows: < 6 months, 39 (24%); 6 to 23 months, 53 (33%); 2 to 4 years, 40 (25%); 5 to 11 years, 15 (9%); and 12 to 17 years, 13 (8%). Fifty-three percent (85 of 160) had an underlying medical condition(s), including a neurologic disorder (n = 36), chronic pulmonary disease (n = 26), genetic disorder (n = 19), cardiac disease (n = 18), prematurity (n = 14), immunocompromised status (n = 12), endocrine/renal disease (n = 2), and other (n = 1). Only 16% (15 of 96) of all patients had received influenza vaccination. Thirty-seven patients had an underlying illness that met existing Advisory Committee on Immunization Practices (ACIP) or American Academy of Pediatrics (AAP) recommendations for immunization, but only 8 had been vaccinated. More than 3 times as many children were reported to be hospitalized in intensive care with influenza in California during the 2003-2004 season compared with the 2004-2005 season. Because children who are younger than 6 months remain at highest risk for severe influenza yet cannot currently be immunized, development and validation of preventive measures for them (eg, maternal immunization, breastfeeding, immunization of young infants and their close contacts) are urgently needed. ACIP's recent recommendation for influenza vaccination of children with conditions that can compromise respiratory function (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, other neuromuscular disorders) is further supported by the frequency of underlying neurologic disease in these cases of severe influenza. A significant proportion of children with severe influenza in California, including children who are aged 2 to 4 years or have underlying genetic syndromes or prematurity, would not have been routinely recommended for influenza vaccination in 2005-2006 ACIP and AAP recommendations, calling into question whether such guidelines should be expanded. Continued surveillance for severe influenza-related morbidity and mortality is important to measure the impact of influenza on children.

Attitudes, Perceived Norms, and Intentions: A Needs Assessment Study of the Influenza Immunization Intentions of Elderly Citizens in Vermont

ERIC Educational Resources Information Center

Bosompra, Kwadwo; Ashikaga, Takamaru; Ruby, Anne

2004-01-01

Influenza and pneumonia rank among the 5 leading causes of death among persons aged 65 and over. Although immunization has been demonstrated to prevent influenza or reduce its incidence and associated complications among the elderly, it has been largely underutilized. Purpose: This study examined the association of attitudes, perceived norms, and…

Original antigenic sin responses to influenza viruses.

PubMed

Kim, Jin Hyang; Skountzou, Ioanna; Compans, Richard; Jacob, Joshy

2009-09-01

Most immune responses follow Burnet's rule in that Ag recruits specific lymphocytes from a large repertoire and induces them to proliferate and differentiate into effector cells. However, the phenomenon of "original antigenic sin" stands out as a paradox to Burnet's rule of B cell engagement. Humans, upon infection with a novel influenza strain, produce Abs against older viral strains at the expense of responses to novel, protective antigenic determinants. This exacerbates the severity of the current infection. This blind spot of the immune system and the redirection of responses to the "original Ag" rather than to novel epitopes were described fifty years ago. Recent reports have questioned the existence of this phenomenon. Hence, we revisited this issue to determine the extent to which original antigenic sin is induced by variant influenza viruses. Using two related strains of influenza A virus, we show that original antigenic sin leads to a significant decrease in development of protective immunity and recall responses to the second virus. In addition, we show that sequential infection of mice with two live influenza virus strains leads to almost exclusive Ab responses to the first viral strain, suggesting that original antigenic sin could be a potential strategy by which variant influenza viruses subvert the immune system.

Cross reactive cellular immune responses in chickens previously exposed to low pathogenic avian influenza

USDA-ARS?s Scientific Manuscript database

Avian influenza (AI) infection in poultry can result in high morbidity and mortality, and negatively affect international trade. Because most AI vaccines used for poultry are inactivated, our knowledge of immunity against AI is based largely on humoral immune responses. In fact, little is known abo...

Recommendations for prevention and control of influenza in children, 2014-2015.

PubMed

2014-11-01

The purpose of this statement is to update recommendations for routine use of seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The American Academy of Pediatrics recommends annual seasonal influenza immunization for all people 6 months and older, including all children and adolescents. Highlights for the upcoming 2014-2015 season include the following:The influenza vaccine composition for the 2014-2015 season is unchanged from the 2013-2014 season.Both trivalent and quadrivalent influenza vaccines are available in the United States for the 2014-2015 season.Annual universal influenza immunization is indicated with either a trivalent or quadrivalent vaccine (no preference).Live attenuated influenza vaccine (LAIV) should be considered for healthy children 2 through 8 years of age who have no contraindications or precautions to the intranasal vaccine. If LAIV is not readily available, inactivated influenza vaccine (IIV) should be used; vaccination should not be delayed to obtain LAIV.The dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age reflects that virus strains in the vaccine have not changed from last season.As always, pediatricians, nurses, and all other health care personnel should be immunized themselves and should promote influenza vaccine use and infection control measures. In addition, pediatricians should promptly identify clinical influenza infections to enable rapid antiviral treatment, when indicated, to reduce morbidity and mortality. Copyright © 2014 by the American Academy of Pediatrics.

Epidemiological Studies to Support the Development of Next Generation Influenza Vaccines.

PubMed

Petrie, Joshua G; Gordon, Aubree

2018-03-26

The National Institute of Allergy and Infectious Diseases recently published a strategic plan for the development of a universal influenza vaccine. This plan focuses on improving understanding of influenza infection, the development of influenza immunity, and rational design of new vaccines. Epidemiological studies such as prospective, longitudinal cohort studies are essential to the completion of these objectives. In this review, we discuss the contributions of epidemiological studies to our current knowledge of vaccines and correlates of immunity, and how they can contribute to the development and evaluation of the next generation of influenza vaccines. These studies have been critical in monitoring the effectiveness of current influenza vaccines, identifying issues such as low vaccine effectiveness, reduced effectiveness among those who receive repeated vaccination, and issues related to egg adaptation during the manufacturing process. Epidemiological studies have also identified population-level correlates of protection that can inform the design and development of next generation influenza vaccines. Going forward, there is an enduring need for epidemiological studies to continue advancing knowledge of correlates of protection and the development of immunity, to evaluate and monitor the effectiveness of next generation influenza vaccines, and to inform recommendations for their use.

Evaluation of the Protective Efficacy of Poly I:C as an Adjuvant for H9N2 Subtype Avian Influenza Inactivated Vaccine and Its Mechanism of Action in Ducks.

PubMed

Zhang, Aiguo; Lai, Hanzhang; Xu, Jiahua; Huang, Wenke; Liu, Yufu; Zhao, Dawei; Chen, Ruiai

2017-01-01

Current commercial H9 avian influenza vaccines cannot provide satisfactory protective immunity against antigenic variant influenza viruses in ducks. Poly I:C, when used as an adjuvant, improves humoral and cellular immunity in many animals but has not been tested in ducks. In this study, we investigated the protective efficacy of Poly I:C as an adjuvant for an inactivated H9N2 Avian influenza vaccine in ducks. We found that an H9N2 vaccine administered with poly I:C (H9-PIC vaccine) induced a significantly more rapid response with higher anti-influenza antibody titers than those of the vaccine alone (H9 vaccine). Moreover, virus shedding was reduced in ducks immunized with the H9-PIC vaccine after challenge with an H9 subtype antigenic variant viruses. IFN-α, IFN-γ, IL-6 and MHC-II mRNA levels were all elevated in ducks receiving the H9-PIC vaccine. In addition, lower expression level of MHC-I may be a reason for inefficient protective ability against heterologous influenza viruses in H9-PIC vaccination of ducks. In conclusion, poly I:C adjuvant enhanced both humoral and cellular immune responses in ducks induced by immunization of inactivated H9N2 vaccine.

Evaluation of the Protective Efficacy of Poly I:C as an Adjuvant for H9N2 Subtype Avian Influenza Inactivated Vaccine and Its Mechanism of Action in Ducks

PubMed Central

Zhang, Aiguo; Lai, Hanzhang; Xu, Jiahua; Huang, Wenke; Liu, Yufu; Zhao, Dawei; Chen, Ruiai

2017-01-01

Current commercial H9 avian influenza vaccines cannot provide satisfactory protective immunity against antigenic variant influenza viruses in ducks. Poly I:C, when used as an adjuvant, improves humoral and cellular immunity in many animals but has not been tested in ducks. In this study, we investigated the protective efficacy of Poly I:C as an adjuvant for an inactivated H9N2 Avian influenza vaccine in ducks. We found that an H9N2 vaccine administered with poly I:C (H9-PIC vaccine) induced a significantly more rapid response with higher anti-influenza antibody titers than those of the vaccine alone (H9 vaccine). Moreover, virus shedding was reduced in ducks immunized with the H9-PIC vaccine after challenge with an H9 subtype antigenic variant viruses. IFN-α, IFN-γ, IL-6 and MHC-II mRNA levels were all elevated in ducks receiving the H9-PIC vaccine. In addition, lower expression level of MHC-I may be a reason for inefficient protective ability against heterologous influenza viruses in H9-PIC vaccination of ducks. In conclusion, poly I:C adjuvant enhanced both humoral and cellular immune responses in ducks induced by immunization of inactivated H9N2 vaccine. PMID:28135294

Human influenza viruses and CD8(+) T cell responses.

PubMed

Grant, Emma J; Quiñones-Parra, Sergio M; Clemens, E Bridie; Kedzierska, Katherine

2016-02-01

Influenza A viruses (IAVs) cause significant morbidity and mortality worldwide, despite new strain-specific vaccines being available annually. As IAV-specific CD8(+) T cells promote viral control in the absence of neutralizing antibodies, and can mediate cross-reactive immunity toward distinct IAVs to drive rapid recovery from both mild and severe influenza disease, there is great interest in developing a universal T cell vaccine. However, despite detailed studies in mouse models of influenza virus infection, there is still a paucity of data on human epitope-specific CD8(+) T cell responses to IAVs. This review focuses on our current understanding of human CD8(+) T cell immunity against distinct IAVs and discusses the possibility of achieving a CD8(+) T cell mediated-vaccine that protects against multiple, distinct IAV strains across diverse human populations. We also review the importance of CD8(+) T cell immunity in individuals highly susceptible to severe influenza infection, including those hospitalised with influenza, the elderly and Indigenous populations. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunologic correlates of protection and potential role for adjuvants to improve influenza vaccines in older adults.

PubMed

McElhaney, Janet E; Coler, Rhea N; Baldwin, Susan L

2013-07-01

The decrease in influenza vaccine efficacy in the elderly is associated with a decline in the stimulation of cell-mediated and cytotoxic T-lymphocyte responses required for clinical protection against influenza, and may be particularly problematic when this population is administered split-virus vaccines that lack conserved viral proteins. Adjuvants, which act through innate immune mechanisms, are known to enhance both humoral and T-cell-mediated responses to influenza vaccines in this population. Adjuvant effects including enhanced antigen presentation, activation and maturation of dendritic cells and production of inflammatory cytokines can drive the desired cell-mediated immune responses. Toll-like receptor ligands comprise one class of adjuvants, which interact with external and internal receptors associated with dendritic cells and other APCs, leading to the regulation and production of important inflammatory cytokines. Potential advances in the production of more effective influenza vaccines for older people include the addition of adjuvants to standard split-virus vaccines and the use of alternate routes of vaccine delivery to augment the response to influenza infection. In this review, the authors discuss the impact of immune senescence on the response to influenza vaccination, the correlates of protection against influenza disease and the progress being made in the design of better influenza vaccines for the population aged 65 years and older.

Protecting patients, protecting healthcare workers: a review of the role of influenza vaccination.

PubMed

Music, T

2012-06-01

Many health authorities recommend routine influenza vaccination for healthcare workers (HCWs), and during the 2009 A (H1N1) pandemic, the World Health Organization (WHO) recommended immunization of all HCWs worldwide. As this remains an important area of policy debate, this paper examines the case for vaccination, the role of local guidelines, barriers to immunization and initiatives to increase uptake. Seasonal influenza is a major threat to public health, causing up to 1 million deaths annually. Extensive evidence supports the vaccination of priority groups, including HCWs. Immunization protects HCWs themselves, and their vulnerable patients from nosocomial influenza infections. In addition, influenza can disrupt health services and impact healthcare organizations financially. Immunization can reduce staff absences, offer cost savings and provide economic benefits. This paper reviews official immunization recommendations and HCW vaccination studies, including a recent International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) survey of 26 countries from each region of the world. HCW immunization is widely recommended and supported by the WHO. In the IFPMA study, 88% of countries recommended HCW vaccination, and 61% supported this financially (with no correlation to country development status). Overall, coverage can be improved, and research shows that uptake may be impacted by lack of conveniently available vaccines and misconceptions regarding vaccine safety/efficacy and influenza risk. Many countries recommend HCW vaccination against influenza. In recent years, there has been an increased uptake rate among HCWs in some countries, but not in others. Several initiatives can increase coverage, including education, easy access to free vaccines and the use of formal declination forms. The case for HCW vaccination is clear, and in an effort to further accelerate uptake as a patient safety measure, an increasing number of healthcare organizations, particularly in the USA, are implementing mandatory immunization policies, similar to other obligatory hygiene measures. However, it would be desirable if similar high vaccination uptake rates could be achieved through voluntary procedures. © 2011 The Author. International Nursing Review © 2011 International Council of Nurses.

Mandatory influenza immunization for health care workers--an ethical discussion.

PubMed

Steckel, Cynthia M

2007-01-01

Influenza is a serious vaccine-preventable disease affecting 20% of the U.S. population each year. Vaccination of high-risk groups has been called the single most important influenza control measure by the Centers for Disease Control and Prevention. Studies show that vaccination can lead to decreases in flu-related illness and absenteeism among health care workers, as well as fewer acute care outbreaks and reduced patient mortality in long-term care settings. However, to date, voluntary programs have achieved only a 40% vaccination rate among health care workers, causing concern among government and infectious disease organizations. This article addresses the ethical justification for mandating influenza vaccination for health care workers. Health care workers' attitudes toward vaccination are presented, as well as historical and legal perspectives on compulsory measures. The ethical principles of effectiveness, beneficence, necessity, autonomy, justice, and transparency are discussed.

Message framing strategies to increase influenza immunization uptake among pregnant African American women.

PubMed

Marsh, Heather A; Malik, Fauzia; Shapiro, Eve; Omer, Saad B; Frew, Paula M

2014-09-01

We explored the attitudes, opinions, and concerns of African American women regarding influenza vaccination during pregnancy. As influenza immunization coverage rates remain suboptimal in the United States among this population, we elicited message framing strategies for multicomponent interventions aimed at decreasing future incident cases of maternal and neonatal influenza. Semi-structured in-depth interviews (N = 21) were conducted with pregnant African American women at urban OB/GYN clinics who had not received an influenza vaccine. Interviews were transcribed, subjected to intercoder reliability assessment, and content analyzed to identify common thematic factors related to acceptance of the influenza vaccine and health communication message preferences. Four major themes were identified. These were communication approaches, normal vaccine behavior, pregnancy vaccination, and positive versus negative framing. Two strong themes emerged: positively-framed messages were preferred over negatively-framed messages and those emphasizing the health of the infant. Additionally, previous immunization, message source, and vaccine misperceptions also played important roles in decision-making. The majority of women indicated that positively framed messages focusing on the infant's health would encourage them to receive an influenza vaccine. Messages emphasizing immunization benefits such as protection against preterm birth and low birth weight outcomes have potential to overcome widespread negative community perceptions and cultural beliefs. Additionally, messages transmitted via interpersonal networks and social media strongly influence motivation to obtain vaccination during pregnancy. The findings of this study will assist in developing tailored messages that change pregnant African American women's influenza vaccination decision-making to achieve improved coverage.

Protective immunity against influenza in HLA-A2 transgenic mice by modified vaccinia virus Ankara vectored vaccines containing internal influenza proteins.

PubMed

Di Mario, Giuseppina; Sciaraffia, Ester; Facchini, Marzia; Gubinelli, Francesco; Soprana, Elisa; Panigada, Maddalena; Bernasconi, Valentina; Garulli, Bruno; Siccardi, Antonio; Donatelli, Isabella; Castrucci, Maria R

2017-03-01

The emergence of novel strains of influenza A viruses with hemagglutinins (HAs) that are antigenically distinct from those circulating in humans, and thus have pandemic potential, pose concerns and call for the development of more broadly protective influenza vaccines. In the present study, modified vaccinia virus Ankara (MVA) encoding internal influenza antigens were evaluated for their immunogenicity and ability to protect HLA-A2.1 transgenic (AAD) mice from infection with influenza viruses. MVAs expressing NP (MVA-NP), M1 (MVA-M1) or polymerase PB1 (MVA-PB1) of A/California/4/09 (CA/09) virus were generated and used to immunize AAD mice. Antibodies and CD8+T cell responses were assessed by ELISA and ELISPOT, respectively, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus. CD8+T cells specific to immunodominant and subdominant epitopes on the internal influenza proteins were elicited by MVA-based vectors in AAD mice, whereas influenza-specific antibodies were detected only in MVA-NP-immunized mice. Both M1- and NP-based MVA vaccines, regardless of whether they were applied individually or in combination, conferred protection against lethal influenza virus challenge. Our data further emphasize the promising potential of MVA vector expressing internal antigens toward the development of a universal influenza vaccine.

The Failure of the 1976 Swine Influenza Immunization Program

PubMed Central

Begley, Sharon L.

1977-01-01

The program to immunize 210 million Americans against swine flu failed. It set back the Federal government's relations with state health agencies, private physicians, pharmaceutical manufacturers, and the insurance industry. It increased mistrust of immunization programs and of government health programs in general. The well-intentioned plan had far-reaching consequences because its scope and the speed with which it was implemented were overreactions to the threat. Its size magnified every one of its faults, legal, medical and political. Organizational and scientific capacity were less than expected. Local health agencies could not administer the program with the inadequate funds from HEW and pharmaceutical companies could not produce a safe, effective children's vaccine. Because of the urgency given the program, Congress neglected the opposition of consumer advocates and state health officials, and did not spend time trying to include immunization against childhood disease in the swine flu program. The failure illustrates the dangers of hasty decisions, of considering only direct medical costs and benefits and not social and political effects on health policy, of launching a public health program whose scientific basis is weak and whose administrative requirements are untested. PMID:610056

Preexisting CD4+ T-Cell Immunity in Human Population to Avian Influenza H7N9 Virus: Whole Proteome-Wide Immunoinformatics Analyses

PubMed Central

Duvvuri, Venkata R.; Duvvuri, Bhargavi; Alice, Christilda; Wu, Gillian E.; Gubbay, Jonathan B.; Wu, Jianhong

2014-01-01

In 2013, a novel avian influenza H7N9 virus was identified in human in China. The antigenically distinct H7N9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. Epitope-specific preexisting T-cell immunity was one of the protective mechanisms in pandemic 2009 H1N1 even in the absence of cross-protective antibodies. Hence, the assessment of preexisting CD4+ T-cell immunity to conserved epitopes shared between H7N9 and human influenza A viruses (IAV) is critical. A comparative whole proteome-wide immunoinformatics analysis was performed to predict the CD4+ T-cell epitopes that are commonly conserved within the proteome of H7N9 in reference to IAV subtypes (H1N1, H2N2, and H3N2). The CD4+ T-cell epitopes that are commonly conserved (∼556) were further screened against the Immune Epitope Database (IEDB) to validate their immunogenic potential. This analysis revealed that 45.5% (253 of 556) epitopes are experimentally proven to induce CD4+ T-cell memory responses. In addition, we also found that 23.3% of CD4+ T-cell epitopes have ≥90% of sequence homology with experimentally defined CD8+ T-cell epitopes. We also conducted the population coverage analysis across different ethnicities using commonly conserved CD4+ T-cell epitopes and corresponding HLA-DRB1 alleles. Interestingly, the indigenous populations from Canada, United States, Mexico and Australia exhibited low coverage (28.65% to 45.62%) when compared with other ethnicities (57.77% to 94.84%). In summary, the present analysis demonstrate an evidence on the likely presence of preexisting T-cell immunity in human population and also shed light to understand the potential risk of H7N9 virus among indigenous populations, given their high susceptibility during previous pandemic influenza events. This information is crucial for public health policy, in targeting priority groups for immunization programs. PMID:24609014

Masking of antigenic epitopes by antibodies shapes the humoral immune response to influenza

PubMed Central

Zarnitsyna, Veronika I.; Ellebedy, Ali H.; Davis, Carl; Jacob, Joshy; Ahmed, Rafi; Antia, Rustom

2015-01-01

The immune responses to influenza, a virus that exhibits strain variation, show complex dynamics where prior immunity shapes the response to the subsequent infecting strains. Original antigenic sin (OAS) describes the observation that antibodies to the first encountered influenza strain, specifically antibodies to the epitopes on the head of influenza's main surface glycoprotein, haemagglutinin (HA), dominate following infection with new drifted strains. OAS suggests that responses to the original strain are preferentially boosted. Recent studies also show limited boosting of the antibodies to conserved epitopes on the stem of HA, which are attractive targets for a ‘universal vaccine’. We develop multi-epitope models to explore how pre-existing immunity modulates the immune response to new strains following immunization. Our models suggest that the masking of antigenic epitopes by antibodies may play an important role in describing the complex dynamics of OAS and limited boosting of antibodies to the stem of HA. Analysis of recently published data confirms model predictions for how pre-existing antibodies to an epitope on HA decrease the magnitude of boosting of the antibody response to this epitope following immunization. We explore strategies for boosting of antibodies to conserved epitopes and generating broadly protective immunity to multiple strains. PMID:26194761

Antibody response to influenza A(H1N1)pdm09 among healthcare personnel receiving trivalent inactivated vaccine: effect of prior monovalent inactivated vaccine.

PubMed

Gaglani, Manjusha; Spencer, Sarah; Ball, Sarah; Song, Juhee; Naleway, Allison; Henkle, Emily; Bozeman, Sam; Reynolds, Sue; Sessions, Wendy; Hancock, Kathy; Thompson, Mark

2014-06-01

Few data are available on the immunogenicity of repeated annual doses of influenza A(H1N1)pdm09-containing vaccines. We enrolled healthcare personnel (HCP) in direct patient care during the autumn of 2010 at 2 centers with voluntary immunization. We verified the receipt of A(H1N1)pdm09-containing monovalent inactivated influenza vaccine (MIIV) and 2010-2011 trivalent inactivated vaccine (TIV). We performed hemagglutination inhibition antibody (HI) assays on preseason, post-TIV, and end-of-season serum samples. We compared the proportion of HCPs with HI titer ≥ 40 against A(H1N1)pdm09 per receipt of prior-season MIIV, current-season TIV, both, or neither. At preseason (n = 1417), HI ≥ 40 was significantly higher among those who received MIIV (34%) vs those who did not (14%) (adjusted relative risk [ARR], 3.26; 95% confidence interval [CI], 2.72-3.81). At post-TIV (n = 865), HI ≥ 40 was lower among HCP who received MIIV and TIV (66%) than among those receiving only TIV (85%) (ARR, 0.93 [95% CI, .84-.997]). At end-of-season (n = 1254), HI ≥ 40 was 40% among those who received both MIIV and TIV and 67% among those receiving only TIV (ARR, 0.76 [95% CI, .65-.88]), 52% among those who received MIIV only, and 12% among those receiving neither. HCP immunization programs should consider effects of host immune response and vaccine antigenic distance on immunogenicity of repeated annual doses of influenza vaccines.

Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays

PubMed Central

Cwach, Kevin T.; Sandbulte, Heather R.; Klonoski, Joshua M.; Huber, Victor C.

2011-01-01

Please cite this paper as: Cwach et al. (2011) Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00283.x. Background  Prior to detection of an antibody response toward influenza viruses using the hemagglutination inhibition assay (HAI), sera are routinely treated to inactivate innate inhibitors using both heat inactivation (56°C) and recombinant neuraminidase [receptor‐destroying enzyme (RDE)]. Objectives  We revisited the contributions of innate serum inhibitors toward interference with influenza viruses in immune assays, using murine sera, with emphasis on the interactions with influenza A viruses of the H3N2 subtype. Methods  We used individual serum treatments: 56°C alone, RDE alone, or RDE + 56°C, to treat sera prior to evaluation within HAI, microneutralization, and macrophage uptake assays. Results  Our data demonstrate that inhibitors present within untreated murine sera interfere with the HAI assay in a manner that is different from that seen for the microneutralization assay. Specifically, the γ class inhibitor α2‐Macroglobulin (A2‐M) can inhibit H3N2 viruses within the HAI assay, but not in the microneutralization assay. Based on these findings, we used a macrophage uptake assay to demonstrate that these inhibitors can increase uptake by macrophages when the influenza viruses express an HA from a 1968 H3N2 virus isolate, but not a 1997 H3N2 isolate. Conclusions  The practice of treating sera to inactivate innate inhibitors of influenza viruses prior to evaluation within immune assays has allowed us to effectively detect influenza virus‐specific antibodies for decades. However, this practice has yielded an under‐appreciation for the contribution of innate serum inhibitors toward host immune responses against these viruses, including contributions toward neutralization and macrophage uptake. PMID:21883963

Possible Impact of Yearly Childhood Vaccination With Trivalent Inactivated Influenza Vaccine (TIV) on the Immune Response to the Pandemic Strain H1N1.

PubMed

Amer, Ahdi; Fischer, Howard; Li, Xiaoming; Asmar, Basim

2016-03-01

Annual vaccination of children against seasonal influenza with trivalent inactivated influenza vaccine (TIV) has shown to be beneficial. However, this yearly practice may have unintended effect. Studies have shown that infection with wild type influenza A viruses can stimulate protective heterotypic immunity against unrelated or new influenza subtypes. We hypothesized that a consequence of yearly TIV vaccination is lack of induction of heterotypic immunity against the recent H1N1 pandemic. This was a retrospective case-control study. We reviewed the medical records of polymerase chain reaction-confirmed cases of 2009 H1N1 influenza infection in children 6 months to 18 years and a matched control group seen during the pandemic. We identified 353 polymerase chain reaction-confirmed H1N1 cases and 396 matching control subjects. Among the H1N1 group, 202/353 (57%) cases received a total of 477 doses of seasonal TIV compared with 218/396 (55%) in the control group who received a total of 435 doses. Seasonal TIV uptake was significantly higher in the H1N1 group 477/548 (87%) than in the control group, 435/532 (81%) (P = .017). Seasonal TIV uptake was significantly higher in H1N1-infected group. The finding suggests that the practice of yearly vaccination with TIV might have negatively affected the immune response against the novel pandemic H1N1 strain. Given the rarity of pandemic novel influenza viruses, and the high predictability of seasonal influenza occurrence, the practice of yearly influenza vaccination should be continued. However, the use of live attenuated intranasal vaccine, as opposed to TIV, may allow for the desirable development of a vigorous heterotypic immune response against future pandemics. © The Author(s) 2015.

Poly I:C adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs.

PubMed

Thomas, Milton; Wang, Zhao; Sreenivasan, Chithra C; Hause, Ben M; Gourapura J Renukaradhya; Li, Feng; Francis, David H; Kaushik, Radhey S; Khatri, Mahesh

2015-01-15

Swine influenza is widely prevalent in swine herds in North America and Europe causing enormous economic losses and a public health threat. Pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. Current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. In this study, we evaluated the protective efficacy of an intranasal Poly I:C adjuvanted UV inactivated bivalent swine influenza vaccine consisting of Swine/OH/24366/07 H1N1 and Swine/CO/99 H3N2, referred as PAV, in maternal antibody positive pigs against an antigenic variant and a heterologous swine influenza virus challenge. Groups of three-week-old commercial-grade pigs were immunized intranasally with PAV or a commercial vaccine (CV) twice at 2 weeks intervals. Three weeks after the second immunization, pigs were challenged with the antigenic variant Swine/MN/08 H1N1 (MN08) and the heterologous Swine/NC/10 H1N2 (NC10) influenza virus. Antibodies in serum and respiratory tract, lung lesions, virus shedding in nasal secretions and virus load in lungs were assessed. Intranasal administration of PAV induced challenge viruses specific-hemagglutination inhibition- and IgG antibodies in the serum and IgA and IgG antibodies in the respiratory tract. Importantly, intranasal administration of PAV provided protection against the antigenic variant MN08 and the heterologous NC10 swine influenza viruses as evidenced by significant reductions in lung virus load, gross lung lesions and significantly reduced shedding of challenge viruses in nasal secretions. These results indicate that Poly I:C or its homologues may be effective as vaccine adjuvants capable of generating cross-protective immunity against antigenic variants/heterologous swine influenza viruses in pigs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection.

PubMed

Berger, Christoph T; Greiff, Victor; Mehling, Matthias; Fritz, Stefanie; Meier, Marc A; Hoenger, Gideon; Conen, Anna; Recher, Mike; Battegay, Manuel; Reddy, Sai T; Hess, Christoph

2015-01-01

Vaccines dramatically reduce infection-related morbidity and mortality. Determining factors that modulate the host response is key to rational vaccine design and demands unsupervised analysis. To longitudinally resolve influenza-specific humoral immune response dynamics we constructed vaccine response profiles of influenza A- and B-specific IgM and IgG levels from 42 healthy and 31 HIV infected influenza-vaccinated individuals. Pre-vaccination antibody levels and levels at 3 predefined time points after vaccination were included in each profile. We performed hierarchical clustering on these profiles to study the extent to which HIV infection associated immune dysfunction, adaptive immune factors (pre-existing influenza-specific antibodies, T cell responses), an innate immune factor (Mannose Binding Lectin, MBL), demographic characteristics (gender, age), or the vaccine preparation (split vs. virosomal) impacted the immune response to influenza vaccination. Hierarchical clustering associated vaccine preparation and pre-existing IgG levels with the profiles of healthy individuals. In contrast to previous in vitro and animal data, MBL levels had no impact on the adaptive vaccine response. Importantly, while HIV infected subjects with low CD4 T cell counts showed a reduced magnitude of their vaccine response, their response profiles were indistinguishable from those of healthy controls, suggesting quantitative but not qualitative deficits. Unsupervised profile-based analysis ranks factors impacting the vaccine-response by relative importance, with substantial implications for comparing, designing and improving vaccine preparations and strategies. Profile similarity between HIV infected and HIV negative individuals suggests merely quantitative differences in the vaccine response in these individuals, offering a rationale for boosting strategies in the HIV infected population.

Socioecological and message framing factors influencing maternal influenza immunization among minority women.

PubMed

Frew, Paula M; Saint-Victor, Diane S; Owens, Lauren E; Omer, Saad B

2014-03-26

A suboptimal level of seasonal influenza vaccination among pregnant minority women is an intractable public health problem, requiring effective message resonance with this population. We evaluated the effects of randomized exposure to messages which emphasize positive outcomes of vaccination ("gain-frame"), or messages which emphasize negative outcomes of forgoing vaccination ("loss-frame"). We also assessed multilevel social and community factors that influence maternal immunization among racially and ethnically diverse populations. Minority pregnant women in metropolitan Atlanta were enrolled in the longitudinal study and randomized to receive intervention or control messages. A postpartum questionnaire administered 30 days postpartum evaluated immunization outcomes following baseline message exposure among the study population. We evaluated key outcomes using bivariate and multivariate analyses. Neither gain- [OR=0.5176, (95% CI: 0.203,1.322)] nor loss-framed [OR=0.5000, 95% CI: (0.192,1.304)] messages were significantly associated with increased likelihood of immunization during pregnancy. Significant correlates of seasonal influenza immunization during pregnancy included healthcare provider recommendation [OR=3.934, 95% CI: (1.331,11.627)], use of hospital-based practices as primary source of prenatal care [OR=2.584, 95% CI: (1.091,6.122)], and perceived interpersonal support for influenza immunization [OR=3.405, 95% CI: (1.412,8.212)]. Dissemination of vaccine education messages via healthcare providers, and cultivating support from social networks, will improve seasonal influenza immunization among pregnant minority women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intranasal Immunization with Influenza Virus-Like Particles Containing Membrane-Anchored Cholera Toxin B or Ricin Toxin B Enhances Adaptive Immune Responses and Protection against an Antigenically Distinct Virus.

PubMed

Ji, Xianliang; Ren, Zhiguang; Xu, Na; Meng, Lingnan; Yu, Zhijun; Feng, Na; Sang, Xiaoyu; Li, Shengnan; Li, Yuanguo; Wang, Tiecheng; Zhao, Yongkun; Wang, Hualei; Zheng, Xuexing; Jin, Hongli; Li, Nan; Yang, Songtao; Cao, Jinshan; Liu, Wensen; Gao, Yuwei; Xia, Xianzhu

2016-04-21

Vaccination is the most effective means to prevent influenza virus infection, although current approaches are associated with suboptimal efficacy. Here, we generated virus-like particles (VLPs) composed of the hemagglutinin (HA), neuraminidase (NA) and matrix protein (M1) of A/Changchun/01/2009 (H1N1) with or without either membrane-anchored cholera toxin B (CTB) or ricin toxin B (RTB) as molecular adjuvants. The intranasal immunization of mice with VLPs containing membrane-anchored CTB or RTB elicited stronger humoral and cellular immune responses when compared to mice immunized with VLPs alone. Administration of VLPs containing CTB or RTB significantly enhanced virus-specific systemic and mucosal antibody responses, hemagglutination inhibiting antibody titers, virus neutralizing antibody titers, and the frequency of virus-specific IFN-γ and IL-4 secreting splenocytes. VLPs with and without CTB or RTB conferred complete protection against lethal challenge with a mouse-adapted homologous virus. When challenged with an antigenically distinct H1N1 virus, all mice immunized with VLPs containing CTB or RTB survived whereas mice immunized with VLPs alone showed only partial protection (80% survival). Our results suggest that membrane-anchored CTB and RTB possess strong adjuvant properties when incorporated into an intranasally-delivered influenza VLP vaccine. Chimeric influenza VLPs containing CTB or RTB may represent promising vaccine candidates for improved immunological protection against homologous and antigenically distinct influenza viruses.

Intranasal Immunization with Influenza Virus-Like Particles Containing Membrane-Anchored Cholera Toxin B or Ricin Toxin B Enhances Adaptive Immune Responses and Protection against an Antigenically Distinct Virus

PubMed Central

Ji, Xianliang; Ren, Zhiguang; Xu, Na; Meng, Lingnan; Yu, Zhijun; Feng, Na; Sang, Xiaoyu; Li, Shengnan; Li, Yuanguo; Wang, Tiecheng; Zhao, Yongkun; Wang, Hualei; Zheng, Xuexing; Jin, Hongli; Li, Nan; Yang, Songtao; Cao, Jinshan; Liu, Wensen; Gao, Yuwei; Xia, Xianzhu

2016-01-01

Vaccination is the most effective means to prevent influenza virus infection, although current approaches are associated with suboptimal efficacy. Here, we generated virus-like particles (VLPs) composed of the hemagglutinin (HA), neuraminidase (NA) and matrix protein (M1) of A/Changchun/01/2009 (H1N1) with or without either membrane-anchored cholera toxin B (CTB) or ricin toxin B (RTB) as molecular adjuvants. The intranasal immunization of mice with VLPs containing membrane-anchored CTB or RTB elicited stronger humoral and cellular immune responses when compared to mice immunized with VLPs alone. Administration of VLPs containing CTB or RTB significantly enhanced virus-specific systemic and mucosal antibody responses, hemagglutination inhibiting antibody titers, virus neutralizing antibody titers, and the frequency of virus-specific IFN-γ and IL-4 secreting splenocytes. VLPs with and without CTB or RTB conferred complete protection against lethal challenge with a mouse-adapted homologous virus. When challenged with an antigenically distinct H1N1 virus, all mice immunized with VLPs containing CTB or RTB survived whereas mice immunized with VLPs alone showed only partial protection (80% survival). Our results suggest that membrane-anchored CTB and RTB possess strong adjuvant properties when incorporated into an intranasally-delivered influenza VLP vaccine. Chimeric influenza VLPs containing CTB or RTB may represent promising vaccine candidates for improved immunological protection against homologous and antigenically distinct influenza viruses. PMID:27110810

Viral vector-based influenza vaccines

PubMed Central

de Vries, Rory D.; Rimmelzwaan, Guus F.

2016-01-01

ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

Viral vector-based influenza vaccines.

PubMed

de Vries, Rory D; Rimmelzwaan, Guus F

2016-11-01

Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.

Distinct immune responses and virus shedding in pigs following aerosol, intra-nasal and contact infection with pandemic swine influenza A virus, A(H1N1)09.

PubMed

Hemmink, Johanneke D; Morgan, Sophie B; Aramouni, Mario; Everett, Helen; Salguero, Francisco J; Canini, Laetitia; Porter, Emily; Chase-Topping, Margo; Beck, Katy; Loughlin, Ronan Mac; Carr, B Veronica; Brown, Ian H; Bailey, Mick; Woolhouse, Mark; Brookes, Sharon M; Charleston, Bryan; Tchilian, Elma

2016-10-20

Influenza virus infection in pigs is a major farming problem, causing considerable economic loss and posing a zoonotic threat. In addition the pig is an excellent model for understanding immunity to influenza viruses as this is a natural host pathogen system. Experimentally, influenza virus is delivered to pigs intra-nasally, by intra-tracheal instillation or by aerosol, but there is little data comparing the outcome of different methods. We evaluated the shedding pattern, cytokine responses in nasal swabs and immune responses following delivery of low or high dose swine influenza pdmH1N1 virus to the respiratory tract of pigs intra-nasally or by aerosol and compared them to those induced in naturally infected contact pigs. Our data shows that natural infection by contact induces remarkably high innate and adaptive immune response, although the animals were exposed to a very low virus dose. In contacts, the kinetics of virus shedding were slow and prolonged and more similar to the low dose directly infected animals. In contrast the cytokine profile in nasal swabs, antibody and cellular immune responses of contacts more closely resemble immune responses in high dose directly inoculated animals. Consideration of these differences is important for studies of disease pathogenesis and assessment of vaccine protective efficacy.

Focusing on flu: Parent perspectives on school-located immunization programs for influenza vaccine.

PubMed

Middleman, Amy B; Short, Mary B; Doak, Jean S

2012-10-01

School-located immunization programs (SLIP) will only be successful if parents consent to their children's participation. It is critical to understand parent perspectives regarding the factors that make them more or less likely to provide that consent. Organizations creating SLIPs will be able to capitalize on the aspects of SLIPs that parents appreciate, and address and correct issues that may give rise to parent concerns. This study involved five focus groups among the parents of school students in a large, urban school district. Findings highlight the broad range of concepts important to parents when considering participation in a SLIP. The safety and trust issues regarding vaccines in general that are so important to parents are also important to parents when considering participation in a SLIP. Effective communication strategies that include assurances regarding tracking of information and the competence and experience of immunizers will be helpful when addressing parents regarding SLIPs. In addition, parents were very cognizant of and positive regarding the public health benefits associated with SLIPs. Further study among larger populations of parents will further refine these ideas and aid in the development of successful influenza vaccine SLIPs that directly address and communicate with parents about the issues most important to them.

Influenza seasonality goes south in the Yucatan Peninsula: The case for a different influenza vaccine calendar in this Mexican region.

PubMed

Ayora-Talavera, Guadalupe; Flores, Gerardo Montalvo-Zurbia; Gómez-Carballo, Jesus; González-Losa, Refugio; Conde-Ferraez, Laura; Puerto-Solís, Marylin; López-Martínez, Irma; Díaz-Quiñonez, Alberto; Barrera-Badillo, Gisela; Acuna-Soto, Rodolfo; Livinski, Alicia A; Alonso, Wladimir J

2017-08-24

While vaccination may be relatively straightforward for regions with a well-defined winter season, the situation is quite different for tropical regions. Influenza activity in tropical regions might be out of phase with the dynamics predicted for their hemispheric group thereby impacting the effectiveness of the immunization campaign. To investigate how the climatic diversity of Mexico hinders its existing influenza immunization strategy and to suggest that the hemispheric vaccine recommendations be tailored to the regional level in order to optimize vaccine effectiveness. We studied the seasonality of influenza throughoutMexico by modeling virological and mortality data.De-trended time series of each Mexican state were analyzed by Fourier decomposition to describe the amplitude and timing of annual influenza epidemic cycles and to compare with each the timing of the WHO's Northern and Southern Hemispheric vaccination schedule. The timings of the primary (major) peaks of both virological and mortality data for most Mexican states are well aligned with the Northern Hemisphere winter (December-February) and vaccine schedule. However, influenza peaks in September in the three states of the Yucatan Peninsula. Influenza-related mortality also peaks in September in Quintana Roo and Yucatan whereas it peaks in May in Campeche. As the current timing of vaccination in Mexico is between October and November, more than half of the annual influenza cases have already occurred in the Yucatan Peninsula states by the time the Northern Hemispheric vaccine is delivered and administered. The current Northern Hemispheric influenza calendar adopted for Mexico is not optimal for the Yucatan Peninsula states thereby likely reducing the effectiveness of the immunization of the population. We recommend that Mexico tailor its immunization strategy to better reflect its climatologic and epidemiological diversity and adopt the WHO Southern Hemisphere influenza vaccine and schedule for the Yucatan Peninsula. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enteric Immunization of Mice Against Influenza with Recombinant Vaccinia

NASA Astrophysics Data System (ADS)

Meitin, Catherine A.; Bender, Bradley S.; Small, Parker A., Jr.

1994-11-01

Intrajejunal administration to mice of a recombinant vaccinia virus containing the influenza virus hemagglutinin gene induced IgA antibody in nasal, gut, and vaginal secretions. It also induced IgG antibody in serum and cell-mediated immunity. The immunization provided significant protection against an influenza virus challenge. This work suggests that enteric-coated recombinant vaccinia could be an orally administered, inexpensive, multivalent, temperature-stable, safe, and effective vaccine for children that could be particularly useful in developing nations, where multiple injections are not easily administered. Oral administration of vaccines should also reduce children's fear of shots at the doctor's office.

Maternal antibodies protect offspring from severe influenza infection and do not lead to detectable interference with subsequent offspring immunization.

PubMed

van der Lubbe, Joan E M; Vreugdenhil, Jessica; Damman, Sarra; Vaneman, Joost; Klap, Jaco; Goudsmit, Jaap; Radošević, Katarina; Roozendaal, Ramon

2017-06-26

Various studies have shown that infants under the age of 6 months are especially vulnerable for complications due to influenza. Currently there are no vaccines licensed for use in this age group. Vaccination of pregnant women during the last trimester, recommended by the WHO as protective measure for this vulnerable female population, may provide protection of newborns at this early age. Although it has been observed that maternal vaccination can passively transfer protection, maternal antibodies could possibly also interfere with subsequent active vaccination of the offspring. Using a mouse model, we evaluated in depth the ability of maternal influenza vaccination to protect offspring and the effect of maternal immunization on the subsequent influenza vaccination of the offspring. By varying the regimen of maternal immunization we explored the impact of different levels of maternal antibodies on the longevity of these antibodies in their progeny. We subsequently assessed to what extent maternal antibodies can mediate direct protection against influenza in their offspring, and whether these antibodies interfere with protection induced by active vaccination of the offspring. The number of immunizations of pregnant mice correlates to the level and longevity of maternal antibodies in the offspring. When these antibodies are present at time of influenza challenge they protect offspring against lethal influenza challenge, even in the absence of detectable HAI titers. Moreover, no detectable interference of passively-transferred maternal antibodies on the subsequent vaccination of the offspring was observed. In the absence of a licensed influenza vaccine for young children, vaccination of pregnant women is a promising measure to provide protection of young infants against severe influenza infection.

Association of School-Based Influenza Vaccination Clinics and School Absenteeism--Arkansas, 2012-2013

ERIC Educational Resources Information Center

Gicquelais, Rachel E.; Safi, Haytham; Butler, Sandra; Smith, Nathaniel; Haselow, Dirk T.

2016-01-01

Background: Influenza is a major cause of seasonal viral respiratory illness among school-aged children. Accordingly, the Arkansas Department of Health (ADH) coordinates >800 school-based influenza immunization clinics before each influenza season. We quantified the relationship between student influenza vaccination in Arkansas public schools…

A genetically adjuvanted influenza B virus vector increases immunogenicity and protective efficacy in mice.

PubMed

Kittel, Christian; Wressnigg, Nina; Shurygina, Anna Polina; Wolschek, Markus; Stukova, Marina; Romanovskaya-Romanko, Ekatherina; Romanova, Julia; Kiselev, Oleg; Muster, Thomas; Egorov, Andrej

2015-10-01

The existence of multiple antigenically distinct types and subtypes of influenza viruses allows the construction of a multivalent vector system for the mucosal delivery of foreign sequences. Influenza A viruses have been exploited successfully for the expression of extraneous antigens as well as immunostimulatory molecules. In this study, we describe the development of an influenza B virus vector whose functional part of the interferon antagonist NS1 was replaced by human interleukin 2 (IL2) as a genetic adjuvant. We demonstrate that IL2 expressed by this viral vector displays immune adjuvant activity in immunized mice. Animals vaccinated with the IL2 viral vector showed an increased hemagglutination inhibition antibody response and higher protective efficacy after challenge with a wild-type influenza B virus when compared to mice vaccinated with a control virus. Our results demonstrate that it is feasible to construct influenza B vaccine strains expressing immune-potentiating foreign sequences from the NS genomic segment. Based on these data, it is now hypothetically possible to create a trivalent (or quadrivalent) live attenuated influenza vaccine in which each component expresses a selected genetic adjuvant with tailored expression levels.

Virus-like Particles Containing Multiple M2 Extracellular Domains Confer Improved Cross-protection Against Various Subtypes of Influenza Virus

PubMed Central

Kim, Min-Chul; Song, Jae-Min; O, Eunju; Kwon, Young-Man; Lee, Youn-Jeong; Compans, Richard W; Kang, Sang-Moo

2013-01-01

The extracellular domain of M2 (M2e), a small ion channel membrane protein, is well conserved among different human influenza A virus strains. To improve the protective efficacy of M2e vaccines, we genetically engineered a tandem repeat of M2e epitope sequences (M2e5x) of human, swine, and avian origin influenza A viruses, which was expressed in a membrane-anchored form and incorporated in virus-like particles (VLPs). The M2e5x protein with the transmembrane domain of hemagglutinin (HA) was effectively incorporated into VLPs at a several 100-fold higher level than that on influenza virions. Intramuscular immunization with M2e5x VLP vaccines was highly effective in inducing M2e-specific antibodies reactive to different influenza viruses, mucosal and systemic immune responses, and cross-protection regardless of influenza virus subtypes in the absence of adjuvant. Importantly, immune sera were found to be sufficient for conferring protection in naive mice, which was long-lived and cross-protective. Thus, molecular designing and presenting M2e immunogens on VLPs provide a promising platform for developing universal influenza vaccines without using adjuvants. PMID:23247101

Protective immunity against H7N3 highly pathogenic avian influenza induced following inoculation of chickens with H7 low pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

In the poultry industry, live virus vaccines are used to induce immunity against numerous respiratory pathogens. These are typically lower virulent forms of virus which are limited in replication and pathology, but induce mucosal, humoral, and cellular immunity. Because of the potential for revers...

Immunity to current H5 highly pathogenic avian influenza viruses: From vaccines to adaptive immunity in wild birds

USDA-ARS?s Scientific Manuscript database

Following the 2014-2015 outbreaks of H5N2 and H5N8 highly pathogenic avian influenza (HPAI) in the U.S., studies were performed to assess the immunity required for protection against future outbreaks should they occur. We assessed the ability of vaccines to induce protection of chickens and turkeys...

Sustained low influenza vaccination in health care workers after H1N1 pandemic: a cross sectional study in an Italian health care setting for at-risk patients.

PubMed

Giannattasio, Antonietta; Mariano, Miriam; Romano, Roberto; Chiatto, Fabrizia; Liguoro, Ilaria; Borgia, Guglielmo; Guarino, Alfredo; Lo Vecchio, Andrea

2015-08-12

Despite consistent recommendations by all Public Health Authorities in support of annual influenza vaccination for at-risk categories, there is still a low uptake of influenza vaccine in these groups including health care workers (HCWs). Aim of this observational two-phase study was to estimate the immunization rates for influenza in four subsequent seasons and for pandemic H1N1 influenza in HCWs of a University Hospital, and to investigate its distribution pattern and the main determinants of immunization. Phase 1 data collection was performed in 2009-2010, during the peak of H1N1 pandemic. Phase 2 data collection, aimed to investigate seasonal influenza vaccination coverage in the three seasons after pandemic, was performed in 2012-2013. The overall H1N1 vaccination rate was derived by the Hospital immunization registry. In 2010, the personnel of three Departments (Infectious Diseases, Pediatrics and Gynecology/Obstetrics) completed a survey on influenza. A second-phase analysis was performed in 2012 to investigate influenza vaccination coverage in three consecutive seasons. The first-phase survey showed a low coverage for influenza in all categories (17 %), with the lowest rate in nurses (8.1 %). A total of 37 % of health care workers received H1N1 vaccine, with the highest rate among physicians and the lowest in nurses. H1N1 vaccination was closely related to the Department, being higher in the Department of Infectious Diseases (53.7 %) and Pediatrics (42.4 %) than in Gynecology/Obstetrics (8.3 %). The second-phase survey showed the lowest rate of influenza vaccination in 2012/13 season. The main reasons for not being vaccinated were "Unsure of the efficacy of vaccine" and "Feel not at-risk of getting influenza or its complications". Despite recommendations, influenza vaccine uptake remains poor. Immunization is largely perceived as a personal protection rather than a measure needed to prevent disease spreading to at-risk patients. Compulsory vaccination against influenza should be considered as a possible strategy, at least in health institutions where at-risk patients are admitted.

A public health initiative to increase annual influenza immunization among hospital health care personnel: the San Diego Hospital Influenza Immunization Partnership.

PubMed

Sawyer, Mark H; Peddecord, K Michael; Wang, Wendy; Deguire, Michelle; Miskewitch-Dzulynsky, Michelle; Vuong, David D

2012-09-01

A public health department-supported intervention to increase influenza immunization among hospital-based health care practitioners (HCPs) in San Diego County took place between 2005 and 2008. The study included all major hospitals in the county, with a population of approximately 3.5 million. Information on hospital activities was collected from before, during and after initiative activities. Vaccination status and demographics were collected directly from HCP using hospital-based and random-dialed telephone surveys. Between 2006 and 2008, hospitals increased promotion activities and reported increases in vaccination rates. Based on the random-dialed surveys, HCP influenza vaccination coverage rates did not increase significantly. Vaccination rates were significantly higher in HCPs who reported that employers provided free vaccination and those who believed that their employers mandated influenza vaccination. This local public health initiative and concurrent state legislation were effective in increasing employer efforts to promote influenza vaccination; however, population-based surveys of HCPs did not show significant increases in influenza vaccination. Overall, this study suggests that public health leadership, intensive employer promotion activities, and state-required declinations alone were not sufficient to significantly increase HCP influenza vaccination. Policymakers and employers should consider mandates to achieve optimal influenza vaccination among HCPs. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Attitudes and perceptions among the pediatric health care providers toward influenza vaccination in Qatar: A cross-sectional study.

PubMed

Alhammadi, Ahmed; Khalifa, Mohamed; Abdulrahman, Hatem; Almuslemani, Eman; Alhothi, Abdullah; Janahi, Mohamed

2015-07-31

Influenza is a communicable but preventable viral illness. Despite safe and effective vaccine availability, compliance rates are globally low. Neither local data on percentage of vaccination nor reasons for poor compliance among pediatric health providers are available in Qatar. To estimate the percentage of vaccinated health care providers at pediatrics department and know their perception and attitudes toward influenza vaccinations. Cross-sectional survey, conducted on 300 pediatrics healthcare professionals from January through April 2013 at the main tertiary teaching hospital in Qatar, included details of demographics, frequency, perceptions and suggestive ways to improve the compliance. From among 230 respondents, 90 physicians and 133 allied health care professionals participated in this survey. Our study showed that percentages of participants who received flu vaccination were 67.7% and those who did not receive vaccination were 32.3%. Allied HCPs (69%) are more likely to get the vaccine compared to the physicians (66%). flu vaccination was approximately 5 times likely to be higher in the age group more than 40 years (P=0.002) compared to age less than or equals 40 years. Overall 70% healthcare providers were willing to recommend immunization to colleagues and patients compared to 30%, who were not willing. The reasons for noncompliance included fear of side effects, contracting the flu, vaccine safety and lack of awareness about the effectiveness. In order to promote immunization, participants believe that use of evidence-based statement, participating in an educational campaign, provides no cost/on site campaigns and leadership support is the most practical interventions. In the present study, the vaccine coverage among pediatrics HCPs seems higher than previously reported rates. Despite their positive attitude toward influenza vaccination, low acceptance and misconceptions of seasonal influenza vaccination by pediatric HCPs may have a negative effect on the successful immunization delivery and children immunization rate. Our findings would be useful for designing and implementing educational programs targeted to improve vaccination coverage rates. Copyright © 2015 Elsevier Ltd. All rights reserved.

An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge.

PubMed

Ma, Ji-Hong; Yang, Fu-Ru; Yu, Hai; Zhou, Yan-Jun; Li, Guo-Xin; Huang, Meng; Wen, Feng; Tong, Guangzhi

2013-07-09

Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses. Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus. Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

Parasite-mediated upregulation of NK cell-derived gamma interferon protects against severe highly pathogenic H5N1 influenza virus infection.

PubMed

O'Brien, Kevin B; Schultz-Cherry, Stacey; Knoll, Laura J

2011-09-01

Outbreaks of influenza A viruses are associated with significant human morbidity worldwide. Given the increasing resistance to the available influenza drugs, new therapies for the treatment of influenza virus infection are needed. An alternative approach is to identify products that enhance a protective immune response. In these studies, we demonstrate that infecting mice with the Th1-inducing parasite Toxoplasma gondii prior to highly pathogenic avian H5N1 influenza virus infection led to decreased lung viral titers and enhanced survival. A noninfectious fraction of T. gondii soluble antigens (STAg) elicited an immune response similar to that elicited by live parasites, and administration of STAg 2 days after H5N1 influenza virus infection enhanced survival, lowered viral titers, and reduced clinical disease. STAg administration protected H5N1 virus-infected mice lacking lymphocytes, suggesting that while the adaptive immune response was not required for enhanced survival, it was necessary for STAg-mediated viral clearance. Mechanistically, we found that administration of STAg led to increased production of gamma interferon (IFN-γ) from natural killer (NK) cells, which were both necessary and sufficient for survival. Further, administration of exogenous IFN-γ alone enhanced survival from H5N1 influenza virus infection, although not to the same level as STAg treatment. These studies demonstrate that a noninfectious T. gondii extract enhances the protective immune response against severe H5N1 influenza virus infections even when a single dose is administered 2 days postinfection.

Influenza and immunization: a quantitative study of media coverage in the season of the «Fluad case».

PubMed

Odone, Anna; Chiesa, Valentina; Ciorba, Veronica; Cella, Paola; Pasquarella, Cesira; Signorelli, Carlo

2015-01-01

Seasonal influenza generates serious health and economic losses. In the last influenza season, the report of three deaths originally blamed on the Fluad vaccine drew widespread attention from the media and is likely to have had a major negative impact on vaccine uptake. We quantitatively analyzed media coverage on influenza and immunization-related topics on all published issues of the Italian newspaper ranking first in circulation, over one year. We retrieved relevant key words and articles, reporting on article topic, length, position, and approach to immunization, and on other selected indicators' summary statistics, trends, and correspondence with key events. Selected key words were retrieved 798 times over the study period, 34% specifically focusing on influenza. The average number of influenza-related key words per issue was 96%higher in the four-day «uncertainty» period from when the deaths were first reported to the release of the test results disproving any causal association between the deaths and the vaccine (time frame #1), as compared to the whole study period. Ninety relevant articles were included in the analysis, 51%focusing on influenza, the average number/issue being 97%higher during time frame #1. During time frame #1, articles were also longer and located in the main sections of the newspapers. No articles were published at the launch of the seasonal influenza immunization campaign. We propose an analytic model of media monitoring that could be effectively applied to support health authorities and representatives of the scientific community in conveying health education messages through the media.

Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets.

PubMed

Music, Nedzad; Reber, Adrian J; Kim, Min-Chul; York, Ian A; Kang, Sang-Moo

2016-01-20

Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine ("Split") alone, influenza split vaccine supplemented with M2e5x VLP ("Split+M2e5x"), M2e5x VLP alone ("M2e5x"), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. Published by Elsevier Ltd.

Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets

PubMed Central

Music, Nedzad; Reber, Adrian J.; Kim, Min-Chul; York, Ian A.; Kang, Sang-Moo

2015-01-01

Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine (“Split”) alone, influenza split vaccine supplemented with M2e5x VLP (“Split+M2e5x”), M2e5x VLP alone (“M2e5x”), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. PMID:26709639

Innate Immunity and the Inter-exposure Interval Determine the Dynamics of Secondary Influenza Virus Infection and Explain Observed Viral Hierarchies.

PubMed

Cao, Pengxing; Yan, Ada W C; Heffernan, Jane M; Petrie, Stephen; Moss, Robert G; Carolan, Louise A; Guarnaccia, Teagan A; Kelso, Anne; Barr, Ian G; McVernon, Jodie; Laurie, Karen L; McCaw, James M

2015-08-01

Influenza is an infectious disease that primarily attacks the respiratory system. Innate immunity provides both a very early defense to influenza virus invasion and an effective control of viral growth. Previous modelling studies of virus-innate immune response interactions have focused on infection with a single virus and, while improving our understanding of viral and immune dynamics, have been unable to effectively evaluate the relative feasibility of different hypothesised mechanisms of antiviral immunity. In recent experiments, we have applied consecutive exposures to different virus strains in a ferret model, and demonstrated that viruses differed in their ability to induce a state of temporary immunity or viral interference capable of modifying the infection kinetics of the subsequent exposure. These results imply that virus-induced early immune responses may be responsible for the observed viral hierarchy. Here we introduce and analyse a family of within-host models of re-infection viral kinetics which allow for different viruses to stimulate the innate immune response to different degrees. The proposed models differ in their hypothesised mechanisms of action of the non-specific innate immune response. We compare these alternative models in terms of their abilities to reproduce the re-exposure data. Our results show that 1) a model with viral control mediated solely by a virus-resistant state, as commonly considered in the literature, is not able to reproduce the observed viral hierarchy; 2) the synchronised and desynchronised behaviour of consecutive virus infections is highly dependent upon the interval between primary virus and challenge virus exposures and is consistent with virus-dependent stimulation of the innate immune response. Our study provides the first mechanistic explanation for the recently observed influenza viral hierarchies and demonstrates the importance of understanding the host response to multi-strain viral infections. Re-exposure experiments provide a new paradigm in which to study the immune response to influenza and its role in viral control.

Innate Immunity and the Inter-exposure Interval Determine the Dynamics of Secondary Influenza Virus Infection and Explain Observed Viral Hierarchies

PubMed Central

Cao, Pengxing; Yan, Ada W. C.; Heffernan, Jane M.; Petrie, Stephen; Moss, Robert G.; Carolan, Louise A.; Guarnaccia, Teagan A.; Kelso, Anne; Barr, Ian G.; McVernon, Jodie; Laurie, Karen L.; McCaw, James M.

2015-01-01

Influenza is an infectious disease that primarily attacks the respiratory system. Innate immunity provides both a very early defense to influenza virus invasion and an effective control of viral growth. Previous modelling studies of virus–innate immune response interactions have focused on infection with a single virus and, while improving our understanding of viral and immune dynamics, have been unable to effectively evaluate the relative feasibility of different hypothesised mechanisms of antiviral immunity. In recent experiments, we have applied consecutive exposures to different virus strains in a ferret model, and demonstrated that viruses differed in their ability to induce a state of temporary immunity or viral interference capable of modifying the infection kinetics of the subsequent exposure. These results imply that virus-induced early immune responses may be responsible for the observed viral hierarchy. Here we introduce and analyse a family of within-host models of re-infection viral kinetics which allow for different viruses to stimulate the innate immune response to different degrees. The proposed models differ in their hypothesised mechanisms of action of the non-specific innate immune response. We compare these alternative models in terms of their abilities to reproduce the re-exposure data. Our results show that 1) a model with viral control mediated solely by a virus-resistant state, as commonly considered in the literature, is not able to reproduce the observed viral hierarchy; 2) the synchronised and desynchronised behaviour of consecutive virus infections is highly dependent upon the interval between primary virus and challenge virus exposures and is consistent with virus-dependent stimulation of the innate immune response. Our study provides the first mechanistic explanation for the recently observed influenza viral hierarchies and demonstrates the importance of understanding the host response to multi-strain viral infections. Re-exposure experiments provide a new paradigm in which to study the immune response to influenza and its role in viral control. PMID:26284917

Breastfeeding--anti-viral potential and relevance to the influenza virus pandemic.

PubMed

Prameela, K K

2011-06-01

Essential nutritive and immunological ingredients abundantly present in breastmilk make it the choice infant nutrition. The uniqueness of mother's milk, in contrast to most therapeutics and immunizations, lies in its potential to adapt itself to the requirements of the infant so that timely immune defenses are tapped from its constituents by immune regulation, modulation and immune acceleration to stimulate novel substances; these render it pertinent as defense when faced with challenging organisms. While it is appreciated that immunity can be transferred from mother to infant through breastmilk following maternal influenza vaccination, the immense benefits conferred by breastfeeding per se during influenza pandemics may not be fully valued. This is substantiated by debates and ambiguities for continued breastfeeding in the face of maternal influenza infections. This article emphasises the utmost importance of breastfeeding in viral pandemics in the light of the changing immunological strategies used by viruses at different times and the urgent need for such opportune defenses. The prolific interaction of its constituents is frequently understated as enormous advantages to the suckling infant.

[Immune response to live influenza vaccine].

PubMed

Naĭkhin, A N; Rekstin, A R; Barantseva, I B; Donina, S A; Desheva, Iu A; Grigor'eva, E P; Kiseleva, I V; Rudenko, L G

2002-01-01

Priority data on the induction, by using a Russian live cold-adapted reassortant influenza vaccine (LIV), of the cellular and humoral immunity with regard for attenuation and genetic reassortment of vaccine stains as well as with regard for the age of vaccinated persons and the production of Th1 (IFNY, IL-2) and Th2 (IL-4) cytokine markers in vitro are presented. It was demonstrated in vivo that a pathogenic virus of the A group by far more actively induced the lymphocyte apoptosis as compared with attenuated genetically reassorted stains. Unlike the influenza pathogenic virus, the genetically attenuated and reassorted strain did not produce any negative effects on the induction of cellular immunity. A comparative study of the LIV immunogenic properties in vaccinated persons showed an advantage of LIV over inactivated influenza vaccine (IIV) in stimulating the cellular and local immunity in the elderly. Unlike IIV, LIV induced an active and balanced immune response developing due to Th1 and Th2 activation. LIV was found to stimulate well enough the production of IFN and IL-2 in both young and old persons.

Protective Cellular Immunity Against Influenza Virus Induced by Plasmid Inoculation of Newborn Mice

PubMed Central

Bot, Adrian; Bot, Simona; García-Sastre, Adolfo

1998-01-01

Neonate organisms display an intrinsic disability to mount effective immune responses to infectious agents or conventional vaccines. Whereas low. doses of antigens trigger a suboptimal response, higher doses are frequently associated with tolerance induction. We investigated the ability of a plasmid-expressing nucleoprotein of influenza virus to prime a specific cellular immune response when administered to newborn mice. We found that persistent exposure to antigen following plasmid inoculation of neonates leads to a vigorous priming of specific CTLs rather than tolerance induction. The CTLs were cross-reactive against multiple strains of type A influenza viruses and produced IFNγ but no IL-4. The immunity triggered by plasmid inoculation of neonates was protective in terms of pulmonary virus clearance as well as survival rate following lethal challenge with influenza virus. Whereas the persistence of the plasmid at the site of injection was readily demonstrable in adult mice at 3 months after inoculation, mice immunized as newborns displayed no plasmid at 3 months and very little at 1 month after injection. Thus, DNA-based immunization of neonates may prove an effective and safe vaccination strategy for induction of cellular immunity against microbes that cause serious infectious diseases in the early period of life. PMID:9851359

Protective effect of a polyvalent influenza DNA vaccine in pigs.

PubMed

Karlsson, Ingrid; Borggren, Marie; Rosenstierne, Maiken Worsøe; Trebbien, Ramona; Williams, James A; Vidal, Enric; Vergara-Alert, Júlia; Foz, David Solanes; Darji, Ayub; Sisteré-Oró, Marta; Segalés, Joaquim; Nielsen, Jens; Fomsgaard, Anders

2018-01-01

Influenza A virus in swine herds represents a major problem for the swine industry and poses a constant threat for the emergence of novel pandemic viruses and the development of more effective influenza vaccines for pigs is desired. By optimizing the vector backbone and using a needle-free delivery method, we have recently demonstrated a polyvalent influenza DNA vaccine that induces a broad immune response, including both humoral and cellular immunity. To investigate the protection of our polyvalent influenza DNA vaccine approach in a pig challenge study. By intradermal needle-free delivery to the skin, we immunized pigs with two different doses (500μg and 800μg) of an influenza DNA vaccine based on six genes of pandemic origin, including internally expressed matrix and nucleoprotein and externally expressed hemagglutinin and neuraminidase as previously demonstrated. Two weeks following immunization, the pigs were challenged with the 2009 pandemic H1N1 virus. When challenged with 2009 pandemic H1N1, 0/5 vaccinated pigs (800μg DNA) became infected whereas 5/5 unvaccinated control pigs were infected. The pigs vaccinated with the low dose (500μg DNA) were only partially protected. The DNA vaccine elicited binding-, hemagglutination inhibitory (HI) - as well as cross-reactive neutralizing antibody activity and neuraminidase inhibiting antibodies in the immunized pigs, in a dose-dependent manner. The present data, together with the previously demonstrated immunogenicity of our influenza DNA vaccine, indicate that naked DNA vaccine technology provides a strong approach for the development of improved pig vaccines, applying realistic low doses of DNA and a convenient delivery method for mass vaccination. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Live attenuated influenza vaccine (LAIV) impacts innate and adaptive immune responses.

PubMed

Lanthier, Paula A; Huston, Gail E; Moquin, Amy; Eaton, Sheri M; Szaba, Frank M; Kummer, Lawrence W; Tighe, Micheal P; Kohlmeier, Jacob E; Blair, Patrick J; Broderick, Michael; Smiley, Stephen T; Haynes, Laura

2011-10-13

Influenza A infection induces a massive inflammatory response in the lungs that leads to significant illness and increases the susceptibility to secondary bacterial pneumonia. The most efficient way to prevent influenza infection is through vaccination. While inactivated vaccines induce protective levels of serum antibodies to influenza hemaglutinin (HA) and neuraminidase (NA) surface proteins, these are strain specific and offer little protection against heterosubtypic influenza viruses. In contrast, live attenuated influenza vaccines (LAIVs) induce a T cell response in addition to antibody responses against HA and NA surface proteins. Importantly, LAIV vaccination induces a response in a mouse model that protects against illness due to heterosubtypic influenza strains. While it is not completely clear what is the mechanism of action of LAIV heterosubtypic protection in humans, it has been shown that LAIV induces heterosubtypic protection in mice that is dependent upon a Type 1 immune response and requires CD8 T cells. In this study, we show that LAIV-induced immunity leads to significantly reduced viral titers and inflammatory responses in the lungs of mice following heterosubtypic infection. Not only are viral titers reduced in LAIV vaccinated mice, the amounts of inflammatory cytokines and chemokines in lung tissue are significantly lower. Additionally, we show that LAIV vaccination of healthy adults also induces a robust Type 1 memory response including the production of chemokines and cytokines involved in T cell activation and recruitment. Thus, our results indicate that LAIV vaccination functions by inducing immune memory which can act to modulate the immune response to subsequent heterosubtypic challenge by influencing both innate and adaptive responses. Copyright © 2011 Elsevier Ltd. All rights reserved.

An active-learning laboratory on immunizations.

PubMed

Donohoe, Krista L; Mawyer, Tonya M; Stevens, J Tyler; Morgan, Laura A; Harpe, Spencer E

2012-12-12

To implement and evaluate an active-learning laboratory activity to teach pharmacy students about influenza, pneumococcal, and shingles vaccines. The laboratory session was divided into 6 immunization stations: 3 stations on influenza including a pediatrics station, and 1 station each for pneumococcal, shingles, and anaphylaxis. Although 118 of 123 (95.9%) students had completed an immunization training certificate prior to attending the laboratory, the average score on a pre-assessment to measure immunization knowledge and confidence was 56%. The post-assessment score was 87.4%. Students' confidence improved by 18.7% to 51.2% in each of the 5 areas assessed. Most respondents rated the activity overall as good or excellent on a post-activity evaluation. An active-learning approach to teaching immunizations allowed students to gain knowledge in simulated real-world experiences and reinforced key concepts on influenza, pneumococcal, and shingles vaccines.

Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial.

PubMed

Davidson, L E; Fiorino, A-M; Snydman, D R; Hibberd, P L

2011-04-01

Live-attenuated influenza vaccine (LAIV) protects against influenza by mucosal activation of the immune system. Studies in animals and adults have demonstrated that probiotics improve the immune response to mucosally delivered vaccines. We hypothesized that Lactobacillus GG (LGG) would function as an immune adjuvant to increase rates of seroconversion after LAIV administration. We conducted a randomized double-blind placebo-controlled pilot study to determine whether LGG improved rates of seroconversion after administration of LAIV. We studied 42 healthy adults during the 2007-2008 influenza season. All subjects received LAIV and then were randomized to LGG or placebo, twice daily for 28 days. Hemagglutinin inhibition titers were assessed at baseline, at day 28 and at day 56 to determine the rates of seroconversion. Subjects were assessed for adverse events throughout the study period. A total of 39 subjects completed the per-protocol analysis. Both LGG and LAIV were well tolerated. Protection rates against the vaccine H1N1 and B strains were suboptimal in subjects receiving LGG and placebo. For the H3N2 strain, 84% receiving LGG vs 55% receiving placebo had a protective titer 28 days after vaccination (odds of having a protective titer was 1.84 95% confidence interval 1.04-3.22, P=0.048). Lactobacillus GG is potential as an important adjuvant to improve influenza vaccine immunogenicity. Future studies of probiotics as immune adjuvants might need to specifically consider examining vaccine-naïve or sero-negative subjects, target mucosal immune responses or focus on groups known to have poor response to influenza vaccines. © 2011 Macmillan Publishers Limited All rights reserved

Serum and mucosal immune responses to an inactivated influenza virus vaccine induced by epidermal powder immunization.

PubMed

Chen, D; Periwal, S B; Larrivee, K; Zuleger, C; Erickson, C A; Endres, R L; Payne, L G

2001-09-01

Both circulating and mucosal antibodies are considered important for protection against infection by influenza virus in humans and animals. However, current inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder delivery system elicits both serum and mucosal antibodies to an inactivated influenza virus vaccine. Serum antibody responses to influenza vaccine following EPI were enhanced by codelivery of cholera toxin (CT), a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the small intestine, trachea, and vaginal tract, although the titers were much lower than the IgG titers. The local origin of the sIgA antibodies was further shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influenza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, whereas a prime and boost immunizations were required for protection in the absence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.

Influenza vaccination coverage among medical residents: an Italian multicenter survey.

PubMed

Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo Giuseppe; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele

2014-01-01

Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P<0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P<0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future.

Influenza virus infection elicits protective antibodies and T cells specific for host cell antigens also expressed as tumor associated antigens: a new view of cancer immunosurveillance

PubMed Central

Iheagwara, Uzoma K.; Beatty, Pamela L.; Van, Phu T.; Ross, Ted M.; Minden, Jonathan S.; Finn, Olivera J.

2014-01-01

Most tumor-associated antigens (TAA) are self-molecules that are abnormally expressed in cancer cells and become targets of antitumor immune responses. Antibodies and T cells specific for some TAA have been found in healthy individuals and are associated with lowered lifetime risk for developing cancer. Lower risk for cancer has also been associated with a history of febrile viral diseases. We hypothesized that virus infections could lead to transient expression of abnormal forms of self-molecules, some of which are TAA; facilitated by the adjuvant effects of infection and inflammation, these molecules could elicit specific antibodies, T cells and lasting immune memory simultaneously with immunity against viral antigens. Such infection-induced immune memory for TAA would be expected to provide life-long immune surveillance of cancer. Using influenza virus infection in mice as a model system, we tested this hypothesis and demonstrated that influenza-experienced mice control 3LL mouse lung tumor challenge better than infection-naive control mice. Using 2D-Difference Gel Electrophoresis (2D-DIGE) and mass spectrometry, we identified numerous molecules, some of which are known TAA, on the 3LL tumor cells recognized by antibodies elicited by two successive influenza infections. We studied in detail immune responses against GAPDH, Histone H4, HSP90, Malate Dehydrogenase 2 and Annexin A2, all of which were overexpressed in influenza-infected lungs and in tumor cells. Lastly, we show that immune responses generated through vaccination against peptides derived from these antigens correlated with improved tumor control. PMID:24778322

State law and influenza vaccination of health care personnel.

PubMed

Stewart, Alexandra M; Cox, Marisa A

2013-01-21

Nosocomial influenza outbreaks, attributed to the unvaccinated health care workforce, have contributed to patient complications or death, worker illness and absenteeism, and increased economic costs to the health care system. Since 1981, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has recommended that all HCP receive an annual influenza vaccination. Health care employers (HCE) have adopted various strategies to encourage health care personnel (HCP) to voluntarily receive influenza vaccination, including: sponsoring educational and promotional campaigns, increasing access to seasonal influenza vaccine, permitting the use of declination statements, and combining multiple approaches. However, these measures failed to significantly increase uptake among HCP. As a result, beginning in 2004, health care facilities and local health departments began to require certain HCP to receive influenza vaccination as a condition of employment and annually. Today, hundreds of facilities throughout the country have developed and implemented similar policies. Mandatory vaccination programs have been endorsed by professional and non-profit organizations, state health departments, and public health. These programs have been more effective at increasing coverage rates than any voluntary strategy, with some health systems reporting coverage rates up to 99.3%. Several states have enacted laws requiring HCEs to implement vaccination programs for the workforce. These laws present an example of how states will respond to threats to the public's health and constrain personal choice in order to protect vulnerable populations. This study analyzes laws in twenty states that address influenza vaccination requirements for HCP who practice in acute or long-term care facilities in the United States. The laws vary in the extent to which they incorporate the six elements of a mandatory HCP influenza vaccination program. Four of the twenty states have adopted a broad definition of HCP or HCE. While 16/20 of the laws require employers to "provide," "arrange for," "ensure," "require" or "offer" influenza vaccinations to HCP, only four states explicitly require HCEs to cover the cost of vaccination. Fifteen of the twenty laws allow HCP to decline the vaccination due to medical contraindication, religious or philosophical beliefs, or by signing a declination statement. Finally, three states address how to sanction noncompliant HCPs. The analysis also discusses the development of a model legal policy that legislators could use as they draft and revise influenza prevention guidelines in health care settings. Copyright © 2012 Elsevier Ltd. All rights reserved.

Investigating the adaptive immune response in influenza and secondary bacterial pneumonia and nanoparticle based therapeutic delivery

NASA Astrophysics Data System (ADS)

Chakravarthy, Krishnan V.

In early 2000, influenza and its associated complications were the 7 th leading cause of death in the United States[1-4]. As of today, this major health problem has become even more of a concern, with the possibility of a potentially devastating avian flu (H5N1) or swine flu pandemic (H1N1). According to the Centers for Disease Control (CDC), over 10 countries have reported transmission of influenza A (H5N1) virus to humans as of June 2006 [5]. In response to this growing concern, the United States pledged over $334 million dollars in international aid for battling influenza[1-4]. The major flu pandemic of the early 1900's provided the first evidence that secondary bacterial pneumonia (not primary viral pneumonia) was the major cause of death in both community and hospital-based settings. Secondary bacterial infections currently account for 35-40% mortality following a primary influenza viral infection [1, 6]. The first component of this work addresses the immunological mechanisms that predispose patients to secondary bacterial infections following a primary influenza viral infection. By assessing host immune responses through various immune-modulatory tools, such as use of volatile anesthetics (i.e. halothane) and Apilimod/STA-5326 (an IL-12/Il-23 transcription blocker), we provide experimental evidence that demonstrates that the overactive adaptive Th1 immune response is critical in mediating increased susceptibility to secondary bacterial infections. We also present data that shows that suppressing the adaptive Th1 immune response enhances innate immunity, specifically in alveolar macrophages, by favoring a pro anti-bacterial phenotype. The second component of this work addresses the use of nanotechnology to deliver therapeutic modalities that affect the primary viral and associated secondary bacterial infections post influenza. First, we used surface functionalized quantum dots for selective targeting of lung alveolar macrophages both in vitro and in vivo. Second, we targeted human bronchial epithelial cells (A549) with gold nanoparticles complexed to 5'PPP-ssRNA to induce RIG-I cytoplasmic ligand, which results in induction of type 1 interferon and concomitant reduction in influenza viral replication. 1-6. Please see dissertation for all references.

Adapting global influenza management strategies to address emerging viruses.

PubMed

Noah, Diana L; Noah, James W

2013-07-15

Death by respiratory complications from influenza infections continues to be a major global health concern. Antiviral drugs are widely available for therapy and prophylaxis, but viral mutations have resulted in resistance that threatens to reduce the long-term utility of approved antivirals. Vaccination is the best method for controlling influenza, but vaccine strategies are blunted by virus antigenic drift and shift. Genetic shift in particular has led to four pandemics in the last century, which have prompted the development of efficient global surveillance and vaccination programs. Although the influenza pandemic of 2009 emphasized the need for the rapid standardization of global surveillance methods and the preparation and dissemination of global assay standards for improved reporting and diagnostic tools, outbreaks of novel influenza strains continue to occur, and current efforts must be enhanced by aggressive public education programs to promote increased vaccination rates in the global population. Recently, a novel H7N9 avian influenza virus with potential to become a pandemic strain emerged in China and was transmitted from animals to humans with a demonstrated >20% mortality rate. Sporadic outbreaks of highly lethal avian virus strains have already increased public awareness and altered annual vaccine production strategies to prevent the natural adaption of this virus to human-to-human transmission. Additional strategies for combating influenza include advancement of new antivirals for unexploited viral or host cellular targets; novel adjuvants and alternate vaccine delivery systems; and development of universal protein, DNA, or multivalent vaccines designed to increase immune responsiveness and enhance public health response times.

The economic burden of influenza-associated outpatient visits and hospitalizations in China: a retrospective survey.

PubMed

Yang, Juan; Jit, Mark; Leung, Kathy S; Zheng, Ya-Ming; Feng, Lu-Zhao; Wang, Li-Ping; Lau, Eric H Y; Wu, Joseph T; Yu, Hong-Jie

2015-10-06

The seasonal influenza vaccine coverage rate in China is only 1.9 %. There is no information available on the economic burden of influenza-associated outpatient visits and hospitalizations at the national level, even though this kind of information is important for informing national-level immunization policy decision-making. A retrospective telephone survey was conducted in 2013/14 to estimate the direct and indirect costs of seasonal influenza-associated outpatient visits and hospitalizations from a societal perspective. Study participants were laboratory-confirmed cases registered in the National Influenza-like Illness Surveillance Network and Severe Acute Respiratory Infections Sentinel Surveillance Network in China in 2013. Patient-reported costs from the survey were validated by a review of hospital accounts for a small sample of the inpatients. The study enrolled 529 outpatients (median age: eight years; interquartile range [IQR]: five to 20 years) and 254 inpatients (median age: four years; IQR: two to seven years). Among the outpatients, 22.1 % (117/529) had underlying diseases and among the inpatients, 52.8 % (134/254) had underlying diseases. The average total costs related to influenza-associated outpatient visits and inpatient visits were US$ 155 (standard deviation, SD US$ 122) and US$ 1,511 (SD US$ 1,465), respectively. Direct medical costs accounted for 45 and 69 % of the total costs related to influenza-associated outpatient and inpatient visits, respectively. For influenza outpatients, the mean cost per episode in children aged below five years (US$ 196) was higher than that in other age groups (US$ 129-153). For influenza inpatients, the mean cost per episode in adults aged over 60 years (US$ 2,735) was much higher than that in those aged below 60 years (US$ 1,417-1,621). Patients with underlying medical conditions had higher costs per episode than patients without underlying medical conditions (outpatients: US$ 186 vs. US$ 146; inpatients: US$ 1,800 vs. US$ 1,189). In the baseline analysis, inpatients reported costs were 18 % higher than those found in the accounts review (n = 38). The economic burden of influenza-associated outpatient and inpatient visits in China is substantial, particularly for young children, the elderly, and patients with underlying medical conditions. More widespread influenza vaccination would likely alleviate the economic burden of patients. The actual impact and cost-effectiveness analysis of the influenza immunization program in China merits further investigation.

Intradermal immunization with inactivated swine influenza virus and adjuvant polydi(sodium carboxylatoethylphenoxy)phosphazene (PCEP) induced humoral and cell-mediated immunity and reduced lung viral titres in pigs.

PubMed

Magiri, Royford; Lai, Ken; Chaffey, Alyssa; Zhou, Yan; Pyo, Hyun-Mi; Gerdts, Volker; Wilson, Heather L; Mutwiri, George

2018-03-14

Swine influenza virus is endemic worldwide and it is responsible for significant economic losses to the swine industry. A vaccine that stimulates a rapid and long-lasting protective immune response to prevent this infection is highly sought. Poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP) has demonstrated adjuvant activity when formulated as part of multiple vaccines in mice and pigs. In this study we examined the magnitude and type of immune response induced in pigs vaccinated via the intramuscular or intradermal routes with inactivated swine influenza virus (SIV) H1N1 vaccine formulated with PCEP. Intradermal administration of PCEP-adjuvanted inactivated SIV vaccine stimulated significant anti-SIV antibody titres, increased neutralizing antibodies, and significantly reduced lung virus load with limited reduction of gross lung lesions after challenge with virulent H1N1 relative to control animals. These results indicate that PCEP may be effective as a vaccine adjuvant against swine influenza viruses in pigs and should be considered a potential candidate adjuvant for future swine intradermal influenza vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Implementation of the influenza vaccination recommendation in nursing homes in Germany : results of a survey as part of the national influenza immunization campaign].

PubMed

Bödeker, B; Wichmann, O; Mertens, B; Seefeld, L; Pott, E

2014-11-01

Residents and staff of nursing homes are important target groups for influenza vaccination in Germany. The aim of this study was to gain the first insights into whether nursing homes organize activities with respect to vaccination against influenza and whether there is a demand for further information. In the context of the national influenza immunization campaign-which is jointly carried out by the Robert Koch Institute (RKI) and the Federal Centre for Health Education (BZgA) on an annual basis-influenza information kits were sent to the management of 10,700 nursing homes in September 2013. Along with the information material, the institutions also received a questionnaire to which they were able to respond via mail, fax, or online. Data from 988 homes were included in the analysis. The majority of institutions informed both residents (88.9 %) and nursing staff (81.2 %) about influenza vaccination. However, only 64.7 % of nursing homes carried out specific immunization activities for their residents and only half (49.3 %) offered a flu shot to their staff. When asked why the institutions do not provide influenza-specific information and vaccination to their staff, the majority had the opinion that this is the responsibility of each individual's general practitioner. Overall, only 4.9 % of nursing homes assessed influenza vaccination coverage among their staff annually. A third of all surveyed institutions (33.6 %) expressed a demand for additional influenza vaccine-related information. In conclusion, improved health education is needed to raise awareness about the importance of influenza vaccination among residents and employees of nursing homes in Germany so as to prevent influenza-associated morbidity and mortality in this risk group.

IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization.

PubMed

Schlaudecker, Elizabeth P; Steinhoff, Mark C; Omer, Saad B; McNeal, Monica M; Roy, Eliza; Arifeen, Shams E; Dodd, Caitlin N; Raqib, Rubhana; Breiman, Robert F; Zaman, K

2013-01-01

Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389). The Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154). The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the cellular and immunologic mechanisms of breast milk-mediated protection after antepartum immunization. ClinicalTrials.gov NCT00142389.

New fronts emerge in the influenza cytokine storm.

PubMed

Guo, Xi-Zhi J; Thomas, Paul G

2017-07-01

Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a "cytokine storm," associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33-amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.

Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: a need for early immune-modulators for severe cases.

PubMed

Lee, Kyung-Yil; Rhim, Jung-Woo; Kang, Jin-Han

2011-01-01

It has been believed that acute lung injury in influenza virus infections is caused by a virus-induced cytopathy; viruses that have multiplied in the upper respiratory tract spread to lung tissues along the lower respiratory tract. However, some experimental and clinical studies have suggested that the pathogenesis of acute lung injury in influenza virus infections is associated with excessive host response including a cell-mediated immune reaction. During the pandemic H1N1 2009 influenza A virus infections in Korea, we experienced a dramatic effect of immune-modulators (corticosteroids) on the patients with severe pneumonia who had significant respiratory distress at presentation and those who showed rapidly progressive pneumonia during oseltamivir treatment. We also found that the pneumonia patients treated with corticosteroids showed the lowest lymphocyte differential and that the severity of pneumonia was associated with the lymphocyte count at presentation. From our findings and previous experimental and clinical studies, we postulated that hyperactive immune cells (T cells) may be involved in the acute lung injury of influenza virus infections, using a hypothesis of 'protein homeostasis system'; the inducers of the cell-mediated immune response are initially produced at the primary immune sites by the innate immune system. These substances reach the lung cells, the main target organ, via the systemic circulation, and possibly the cells of other organs, including myocytes or central nerve system cells, leading to extrapulmonary symptoms (e.g., myalgia and rhabdomyolysis, and encephalopathy). To control these substances that may be possibly toxic to host cells, the adaptive immune reaction may be operated by immune cells, mainly lymphocytes. Hyperimmune reaction of immune cells produces higher levels of cytokines which may be associated with acute lung injury, and may be controlled by early use of immune-modulators. Early initiation and proper dosage of immune-modulators with antiviral agents for severe pneumonia patients may reduce morbidity and prevent progressive fatal pneumonia. Copyright © 2010 Elsevier Ltd. All rights reserved.

Diversifying Selection Analysis Predicts Antigenic Evolution of 2009 Pandemic H1N1 Influenza A Virus in Humans.

PubMed

Lee, Alexandra J; Das, Suman R; Wang, Wei; Fitzgerald, Theresa; Pickett, Brett E; Aevermann, Brian D; Topham, David J; Falsey, Ann R; Scheuermann, Richard H

2015-05-01

Although a large number of immune epitopes have been identified in the influenza A virus (IAV) hemagglutinin (HA) protein using various experimental systems, it is unclear which are involved in protective immunity to natural infection in humans. We developed a data mining approach analyzing natural H1N1 human isolates to identify HA protein regions that may be targeted by the human immune system and can predict the evolution of IAV. We identified 16 amino acid sites experiencing diversifying selection during the evolution of prepandemic seasonal H1N1 strains and found that 11 sites were located in experimentally determined B-cell/antibody (Ab) epitopes, including three distinct neutralizing Caton epitopes: Sa, Sb, and Ca2 [A. J. Caton, G. G. Brownlee, J. W. Yewdell, and W. Gerhard, Cell 31:417-427, 1982, http://dx.doi.org/10.1016/0092-8674(82)90135-0]. We predicted that these diversified epitope regions would be the targets of mutation as the 2009 H1N1 pandemic (pH1N1) lineage evolves in response to the development of population-level protective immunity in humans. Using a chi-squared goodness-of-fit test, we identified 10 amino acid sites that significantly differed between the pH1N1 isolates and isolates from the recent 2012-2013 and 2013-2014 influenza seasons. Three of these sites were located in the same diversified B-cell/Ab epitope regions as identified in the analysis of prepandemic sequences, including Sa and Sb. As predicted, hemagglutination inhibition (HI) assays using human sera from subjects vaccinated with the initial pH1N1 isolate demonstrated reduced reactivity against 2013-2014 isolates. Taken together, these results suggest that diversifying selection analysis can identify key immune epitopes responsible for protective immunity to influenza virus in humans and thereby predict virus evolution. The WHO estimates that approximately 5 to 10% of adults and 20 to 30% of children in the world are infected by influenza virus each year. While an adaptive immune response helps eliminate the virus following acute infection, the virus rapidly evolves to evade the established protective memory immune response, thus allowing for the regular seasonal cycles of influenza virus infection. The analytical approach described here, which combines an analysis of diversifying selection with an integration of immune epitope data, has allowed us to identify antigenic regions that contribute to protective immunity and are therefore the key targets of immune evasion by the virus. This information can be used to determine when sequence variations in seasonal influenza virus strains have affected regions responsible for protective immunity in order to decide when new vaccine formulations are warranted. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.

PubMed

Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C

2015-10-27

The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of exposure to infectious agents, while adaptive immunity takes several days to become effective. Here we show, by using a simple lipopeptide-based TLR2 agonist, that an influenza detergent-split vaccine can be made to simultaneously stimulate and amplify both systems to provide immediate antiviral protection while giving the adaptive immune system time to implement long-term immunity. Both types of immunity induced by this approach protect against vaccine-matched as well as unrelated virus strains and potentially even against strains yet to be encountered. Conferring dual functionality to influenza vaccines is beneficial for improving community protection, particularly during periods between the onset of an outbreak and the time when a vaccine becomes available or in scenarios in which mass vaccination with a strain to which the population is immunologically naive is imperative. Copyright © 2015 Chua et al.

Intranasal co-administration of 1,8-cineole with influenza vaccine provide cross-protection against influenza virus infection.

PubMed

Li, Yun; Xu, Yu-Ling; Lai, Yan-Ni; Liao, Shang-Hui; Liu, Ni; Xu, Pei-Ping

2017-10-15

Vaccination is the most efficient means for protection against influenza. However, the various vaccines have low efficacy to protect against pandemic strains because of antigenic drift and recombination of influenza virus. Adjuvant therapy is one of the attempts to improve influenza vaccine effective cross-protection against influenza virus infection. Our previous study confirmed that 1,8-cineole inhibits the NF-κB, reduces pro-inflammatory cytokines, and relieves the pathological changes of viral pneumonia in mice infected with influenza virus. 1,8-cineole, administered via intranasal (i.n.) route, may also have the capacity to be an adjuvant of the influenza vaccine. This study was designed to investigate the potential use of i.n. co-administration of 1,8-cineole, a major component of the Eucalyptus essential oils, with influenza vaccine and whether could provide cross-protection against influenza virus infection in a mouse model. I.n. co-administration of 1,8-cineole in two doses (6.25 and 12.5 mg/kg) with influenza vaccine was investigated in a mouse model in order to see whether it could provide cross-protection against influenza virus infection. The mice were intranasally immunized three times at the 0, 7 and 14 day with vaccine containing 0.2 µg hemagglutinin (HA) and/or without 1,8-cineole. Seven days after the 3rd immunization dose, the mice were infected with 50 µl of 15 LD 50 (50% mouse lethal dose) influenza virus A/FM/1/47 (H1N1). On day 6 post-infection, 10 mice per group were sacrificed to collect samples, to take the body weight and lung, and detect the viral load, pathological changes in the lungs and antibody, etc. The collected samples included blood serum and nasal lavage fluids. In addition, the survival experiments were carried out  to investigate the survival of mice. Mice i.n. inoculated with influenza vaccine and 12.5 mg/kg 1,8-cineole increased the production of influenza-specific serum immunoglobulin (Ig) G2a antibodies, stimulated mucosal secretive IgA (s-IgA) responses at the nasal cavity, improved the expression of respiratory tract intraepithelial lymphocytes (IELs) in the upper respiratory tract, and promoted dendritic cell (DC) maturation and the expression of co-stimulatory molecules cluster of differentiation (CD)40, CD80 and CD86 in peripheral blood. Importantly, mice that had received 1,8-cineole-supplemented influenza vaccine showed longer survival time, milder inflammation, less weight loss and mortality rate and lower lung index and viral titers compared to that of mice immunized a non-1,8-cineole-adjuvanted split vaccine. Thus, i.n. immunization with 1,8-cineole-adjuvanted vaccine induces a superior cross-protective immunity against infection with influenza than an inactivated vaccine only. These results suggest that 1,8-cineole (12.5 mg/kg) has a cross-protection against influenza virus, co-administered with inactivated influenza viral antigen in a mouse model. Copyright © 2017 Elsevier GmbH. All rights reserved.

Immunization with M2e-Displaying T7 Bacteriophage Nanoparticles Protects against Influenza A Virus Challenge

PubMed Central

Hashemi, Hamidreza; Pouyanfard, Somayeh; Bandehpour, Mojgan; Noroozbabaei, Zahra; Kazemi, Bahram; Saelens, Xavier; Mokhtari-Azad, Talat

2012-01-01

Considering the emergence of highly pathogenic influenza viruses and threat of worldwide pandemics, there is an urgent need to develop broadly-protective influenza vaccines. In this study, we demonstrate the potential of T7 bacteriophage-based nanoparticles with genetically fused ectodomain of influenza A virus M2 protein (T7-M2e) as a candidate universal flu vaccine. Immunization of mice with non-adjuvanted T7-M2e elicited M2e-specific serum antibody responses that were similar in magnitude to those elicited by M2e peptide administered in Freund’s adjuvant. Comparable IgG responses directed against T7 phage capsomers were induced following vaccination with wild type T7 or T7-M2e. T7-M2e immunization induced balanced amounts of IgG1 and IgG2a antibodies and these antibodies specifically recognized native M2 on the surface of influenza A virus-infected mammalian cells. The frequency of IFN-γ-secreting T cells induced by T7-M2e nanoparticles was comparable to those elicited by M2e peptide emulsified in Freund’s adjuvant. Emulsification of T7-M2e nanoparticles in Freund’s adjuvant, however, induced a significantly stronger T cell response. Furthermore, T7-M2e-immunized mice were protected against lethal challenge with an H1N1 or an H3N2 virus, implying the induction of hetero-subtypic immunity in our mouse model. T7-M2e-immunized mice displayed considerable weight loss and had significantly reduced viral load in their lungs compared to controls. We conclude that display of M2e on the surface of T7 phage nanoparticles offers an efficient and economical opportunity to induce cross-protective M2e-based immunity against influenza A. PMID:23029232

Influenza vaccination acceptance among diverse pregnant women and its impact on infant immunization

PubMed Central

Frew, Paula M; Zhang, Siyu; Saint-Victor, Diane S; Schade, Ashley C; Benedict, Samantha; Banan, Maral; Ren, Xiang; Omer, Saad B

2013-01-01

Objective: We examined pregnant women’s likelihood of vaccinating their infants against seasonal influenza via a randomized message framing study. Using Prospect Theory, we tested gain- and loss-frame message effects and demographic and psychosocial correlates of influenza immunization intention. We also explored interactions among pregnant women who viewed “Contagion” to understand cultural influences on message perception. Methods: Pregnant women ages 18–50 participated in a randomized message framing study from September 2011 through May 2012 that included exposure to intervention or control messages, coupled with questionnaire completion. Venue-based sampling was used to recruit racial and ethnic minority female participants at locations throughout Atlanta, Georgia. Bivariate and multivariate analyses were conducted to evaluate key outcomes. Results: The study population (n = 261) included many lower income (≤ $20 000/yearly household earnings) pregnant participants (69.2%, n = 171) inclusive of Black/African Americans (88.5%, n = 230), Hispanic/Latinas (7.3%, n = 19), and Other/Multicultural women (4.2%, n = 11). Both gain [OR = 2.13, 90% CI: (1.120, 4.048)] and loss-frame messages [OR = 2.02, 90% CI: (1.083, 3.787)] were significantly associated with infant influenza vaccination intention compared with the control condition. Intention to immunize against influenza during pregnancy had a strong effect on intent to immunize infants [OR = 10.83, 90%CI: (4.923, 23.825)]. Those who had seen the feature film “Contagion” (n = 54, 20.69%) viewed gain- and loss-framed messages as appealing (x2 = 6.03, p = 0.05), novel (x2 = 6.24, p = 0.03), and easy to remember (x2 = 16.33, P = 0.0003). Conclusions: In this population, both gain- and loss-framed messages were positively associated with increased maternal intent to immunize infants against influenza. Message resonance was enhanced among those who saw the film “Contagion.” Additionally, history of immunization was strongly associated with infant immunization intention. PMID:24172064

In Vivo Imaging of Influenza Virus Infection in Immunized Mice

PubMed Central

Czakó, Rita; Vogel, Leatrice; Lamirande, Elaine W.; Bock, Kevin W.; Moore, Ian N.; Ellebedy, Ali H.; Ahmed, Rafi

2017-01-01

ABSTRACT Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter virus, we demonstrate the application of noninvasive in vivo imaging system (IVIS) technology to evaluate the preclinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence in groups of mice passively or actively immunized by various strategies that accelerated the clearance of the challenge virus at different rates and by distinct mechanisms. Imaging findings were consistent with conclusions derived from virus titers in the lungs and, notably, were more informative than conventional efficacy endpoints in some cases. Our findings demonstrate the reliability of IVIS as a qualitative approach to support preclinical evaluation of candidate medical countermeasures for influenza in mice. PMID:28559489

Factors Influencing the Decision to Receive an Influenza Vaccination Among Manufacturing Plant and Day Care Center Employees.

PubMed

McKeirnan, Kimberly C

2016-05-01

To improve influenza immunization rates, it is essential to understand why adults are not immunized and the factors that influence their decisions. This information can be used to tailor educational materials and outreach. © 2016 The Author(s).

Mucosal immune response in broilers following vaccination with inactivated influenza and recombinant Bacillus subtilis

USDA-ARS?s Scientific Manuscript database

Mucosal and systemic immunity were observed in broilers vaccinated with mannosylated chitosan adjuvated (MCA) inactivated A/Turkey/Virginia/158512/2002 (H7N2) and administered with and without recombinant Bacillus subtilis to elicit heterologous influenza strain protection. Previously, mucosal immu...

Evolution of equine influenza virus in vaccinated horses.

PubMed

Murcia, Pablo R; Baillie, Gregory J; Stack, J Conrad; Jervis, Carley; Elton, Debra; Mumford, Jennifer A; Daly, Janet; Kellam, Paul; Grenfell, Bryan T; Holmes, Edward C; Wood, James L N

2013-04-01

Influenza A viruses are characterized by their ability to evade host immunity, even in vaccinated individuals. To determine how prior immunity shapes viral diversity in vivo, we studied the intra- and interhost evolution of equine influenza virus in vaccinated horses. Although the level and structure of genetic diversity were similar to those in naïve horses, intrahost bottlenecks may be more stringent in vaccinated animals, and mutations shared among horses often fall close to putative antigenic sites.

Defense Health Care. Comprehensive Oversight Framework Needed to Help Ensure Effective Implementation of a Deployment Health Quality Assurance Program

DTIC Science & Technology

2007-06-01

Virus IPV Inactivated Poliovirus MMR Measles, Mumps, and Rubella This is a work of the U.S. government and is not subject to copyright protection...rubella), inactivated poliovirus (IPV), hepatitis B, and influenza (once per season). • Pass: all immunizations current • Fail: overdue for one or more

Apoptosis and other immune biomarkers predict influenza vaccine responsiveness.

PubMed

Furman, David; Jojic, Vladimir; Kidd, Brian; Shen-Orr, Shai; Price, Jordan; Jarrell, Justin; Tse, Tiffany; Huang, Huang; Lund, Peder; Maecker, Holden T; Utz, Paul J; Dekker, Cornelia L; Koller, Daphne; Davis, Mark M

2013-04-16

Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to identifying such markers, we used influenza vaccination in 30 young (20-30 years) and 59 older subjects (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation. Using machine learning, we identified nine variables that predict the antibody response with 84% accuracy. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health.

A cross-immunization model for the extinction of old influenza strains.

PubMed

Uekermann, Florian; Sneppen, Kim

2016-05-13

Given the frequent mutation of antigenic features, the constancy of genetic and antigenic diversity of influenza within a subtype is surprising. While the emergence of new strains and antigenic features is commonly attributed to selection by the human immune system, the mechanism that ensures the extinction of older strains remains controversial. To replicate this dynamics of replacement current models utilize mechanisms such as short-lived strain-transcending immunity, a direct competition for hosts, stochastic extinction or constrained antigenic evolution. Building on the idea of short-lived immunity we introduce a minimal model that exhibits the aforementioned dynamics of replacement. Our model relies only on competition due to an antigen specific immune-response in an unconstrained antigenic space. Furthermore the model explains the size of typical influenza epidemics as well as the tendency that new epidemics are associated with mutations of old antigens.

Influenza-induced type I interferon enhances susceptibility to gram-negative and gram-positive bacterial pneumonia in mice.

PubMed

Lee, Benjamin; Robinson, Keven M; McHugh, Kevin J; Scheller, Erich V; Mandalapu, Sivanarayana; Chen, Chen; Di, Y Peter; Clay, Michelle E; Enelow, Richard I; Dubin, Patricia J; Alcorn, John F

2015-07-15

Suppression of type 17 immunity by type I interferon (IFN) during influenza A infection has been shown to enhance susceptibility to secondary bacterial pneumonia. Although this mechanism has been described in coinfection with gram-positive bacteria, it is unclear whether similar mechanisms may impair lung defense against gram-negative infections. Furthermore, precise delineation of the duration of type I IFN-associated susceptibility to bacterial infection remains underexplored. Therefore, we investigated the effects of preceding influenza A virus infection on subsequent challenge with the gram-negative bacteria Escherichia coli or Pseudomonas aeruginosa and the temporal association between IFN expression with susceptibility to Staphylococcus aureus challenge in a mouse model of influenza and bacterial coinfection. Here we demonstrate that preceding influenza A virus led to increased lung E. coli and P. aeruginosa bacterial burden, which was associated with suppression of type 17 immunity and attenuation of antimicrobial peptide expression. Enhanced susceptibility to S. aureus coinfection ceased at day 14 of influenza infection, when influenza-associated type I IFN levels had returned to baseline levels, further suggesting a key role for type I IFN in coinfection pathogenesis. These findings further implicate type I IFN-associated suppression of type 17 immunity and antimicrobial peptide production as a conserved mechanism for enhanced susceptibility to both gram-positive and gram-negative bacterial coinfection during influenza infection. Copyright © 2015 the American Physiological Society.

Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus:S. pyogenes super-infection

PubMed Central

Klonoski, Joshua M.; Hurtig, Heather R.; Juber, Brian A.; Schuneman, Margaret J.; Bickett, Thomas E.; Svendsen, Joshua M.; Burum, Brandon; Penfound, Thomas A.; Sereda, Grigoriy; Dale, James B.; Chaussee, Michael S.; Huber, Victor C.

2014-01-01

Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The β-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus:S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus:S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus:S. pyogenes super-infection model, despite the fact that all M protein-vaccinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection. PMID:25077423

Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses.

PubMed

Carter, Donald M; Darby, Christopher A; Johnson, Scott K; Carlock, Michael A; Kirchenbaum, Greg A; Allen, James D; Vogel, Thorsten U; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold; Ross, Ted M

2017-12-15

Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long-lasting protective immune responses. The goal of these vaccines is to stimulate immune responses that react against most, if not all, circulating influenza strains, over a long period of time in all populations of people. Commonly, these experimental vaccines are tested in naive animal models that do not have anti-influenza immune responses; however, humans have preexisting immunity to influenza viral antigens, particularly antibodies to the HA and NA glycoproteins. Therefore, this study investigated how preexisting antibodies to historical influenza viruses influenced HAI-specific antibodies and protective efficacy using a broadly protective vaccine candidate. Copyright © 2017 American Society for Microbiology.

Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

PubMed Central

Carter, Donald M.; Darby, Christopher A.; Johnson, Scott K.; Carlock, Michael A.; Kirchenbaum, Greg A.; Allen, James D.; Vogel, Thorsten U.; Delagrave, Simon; DiNapoli, Joshua; Kleanthous, Harold

2017-01-01

ABSTRACT Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long-lasting protective immune responses. The goal of these vaccines is to stimulate immune responses that react against most, if not all, circulating influenza strains, over a long period of time in all populations of people. Commonly, these experimental vaccines are tested in naive animal models that do not have anti-influenza immune responses; however, humans have preexisting immunity to influenza viral antigens, particularly antibodies to the HA and NA glycoproteins. Therefore, this study investigated how preexisting antibodies to historical influenza viruses influenced HAI-specific antibodies and protective efficacy using a broadly protective vaccine candidate. PMID:28978709

Generation and testing anti-influenza human monoclonal antibodies in a new humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO. IL-2Rγc KO. NOD).

PubMed

Mendoza, Mirian; Ballesteros, Angela; Qiu, Qi; Pow Sang, Luis; Shashikumar, Soumya; Casares, Sofia; Brumeanu, Teodor-D

2018-02-01

Pandemic outbreaks of influenza type A viruses have resulted in numerous fatalities around the globe. Since the conventional influenza vaccines (CIV) provide less than 20% protection for individuals with weak immune system, it has been considered that broadly cross-neutralizing antibodies may provide a better protection. Herein, we showed that a recently generated humanized mouse (DRAGA mouse; HLA-A2. HLA-DR4. Rag1KO. IL-2Rgc KO. NOD) that lacks the murine immune system and expresses a functional human immune system can be used to generate cross-reactive, human anti-influenza monoclonal antibodies (hu-mAb). DRAGA mouse was also found to be suitable for influenza virus infection, as it can clear a sub-lethal infection and sustain a lethal infection with PR8/A/34 influenza virus. The hu-mAbs were designed for targeting a human B-cell epitope ( 180 WGIHHPPNSKEQ QNLY 195 ) of hemagglutinin (HA) envelope protein of PR8/A/34 (H1N1) virus with high homology among seven influenza type A viruses. A single administration of HA 180-195 specific hu-mAb in PR8-infected DRAGA mice significantly delayed the lethality by reducing the lung damage. The results demonstrated that DRAGA mouse is a suitable tool to (i) generate heterotype cross-reactive, anti-influenza human monoclonal antibodies, (ii) serve as a humanized mouse model for influenza infection, and (iii) assess the efficacy of anti-influenza antibody-based therapeutics for human use.

Key points in evaluating immunogenicity of pandemic influenza vaccines: A lesson from immunogenicity studies of influenza A(H1N1)pdm09 vaccine.

PubMed

Ohfuji, Satoko; Kobayashi, Masayuki; Ide, Yuichiro; Egawa, Yumi; Saito, Tomoko; Kondo, Kyoko; Ito, Kazuya; Kase, Tetsuo; Maeda, Akiko; Fukushima, Wakaba; Hirota, Yoshio

2017-09-18

Immunogenicity studies on pandemic influenza vaccine are necessary to inform rapid development and implementation of a vaccine during a pandemic. Thus, strategies for immunogenicity assessment are required. To identify essential factors to consider when evaluating the immunogenicity of pandemic influenza vaccines using the experience in Japan with the influenza A(H1N1)pdm09 vaccine. We conducted a search of observational studies using PubMed and IchushiWeb. Search terms included "influenza vaccine AND (immunogenicity OR immune response) AND Japan AND (2009 OR pdm09) NOT review," and was limited to studies conducted in humans. A total of 33 articles were identified, of which 16 articles met the inclusion criteria. Immunogenicity of the commercially available influenza A(H1N1)pdm09 vaccine satisfied the international criteria for influenza vaccine immunogenicity in all study populations. The most remarkable immune response was observed in junior high school students, while the lowest immune response was observed in hematological malignancy patients. Similar to immunogenicity studies on seasonal influenza vaccines, factors such as patient background (e.g., age, underlying condition, pre-vaccination titer, body mass index, etc.) and study procedure (e.g., concurrent measurement of pre- and post-vaccination antibody titer, effects of infection during the study period) may have affected the assessment of immunogenicity to the influenza A(H1N1)pdm09 vaccine. In addition, prior vaccination with the seasonal influenza vaccine may inhibit antibody induction by the influenza A(H1N1)pdm09 vaccine. This review discusses factors and strategies that must be considered and addressed during immunogenicity assessments of pandemic influenza vaccines, which may provide useful information for future influenza pandemics. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations.

PubMed Central

Fynan, E F; Webster, R G; Fuller, D H; Haynes, J R; Santoro, J C; Robinson, H L

1993-01-01

Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been tested for their ability to raise protective immunity against lethal influenza challenges of the same subtype. In trials using two inoculations of from 50 to 300 micrograms of purified DNA in saline, 67-95% of test mice and 25-63% of test chickens have been protected against a lethal influenza challenge. Parenteral routes of inoculation that achieved good protection included intramuscular and intravenous injections. Successful mucosal routes of vaccination included DNA drops administered to the nares or trachea. By far the most efficient DNA immunizations were achieved by using a gene gun to deliver DNA-coated gold beads to the epidermis. In mice, 95% protection was achieved by two immunizations with beads loaded with as little as 0.4 micrograms of DNA. The breadth of routes supporting successful DNA immunizations, coupled with the very small amounts of DNA required for gene-gun immunizations, highlight the potential of this remarkably simple technique for the development of subunit vaccines. Images Fig. 1 PMID:8265577

Influenza vaccines based on virus-like particles

PubMed Central

Kang, Sang-Moo; Song, Jae-Min; Quan, Fu-Shi; Compans, Richard W.

2009-01-01

The simultaneous expression of structural proteins of virus can produce virus-like particles (VLPs) by a self-assembly process in a viral life cycle even in the absence of genomic material. Taking an advantage of structural and morphological similarities of VLPs to native virions, VLPs have been suggested as a promising platform for new viral vaccines. In the light of a pandemic threat, influenza VLPs have been recently developed as a new generation of non-egg based cell culture-derived vaccine candidates against influenza infection. Animals vaccinated with VLPs containing hemagglutinin (HA) or HA and neuraminidase (NA) were protected from morbidity and mortality resulting from lethal influenza infections. Influenza VLPs serve as an excellent model system of an enveloped virus for understanding the properties of VLPs in inducing protective immunity. In this review, we briefly describe the characteristics of influenza VLPs assembled with a lipid bilayer containing glycoproteins, and summarize the current progress on influenza VLPs as an alternative vaccine candidate against seasonal as well as pandemic influenza viruses. In addition, the protective immune correlates induced by vaccination with influenza VLPs are discussed. PMID:19374929

Outcome of influenza vaccination in combat-related post-traumatic stress disorder (PTSD) patients

PubMed Central

Kosor Krnic, E; Gagro, A; Kozaric-Kovacic, D; Vilibic, M; Grubisic-Ilic, M; Folnegovic-Smalc, V; Drazenovic, V; Cecuk-Jelicic, E; Gjenero-Margan, I; Kuzman, I; Jeren, T; Sabioncello, A; Kerhin-Brkljacic, V; Kaic, B; Markotic, A; Gotovac, K; Rabatic, S; Mlinaric-Galinovic, G; Dekaris, D

2007-01-01

Post-traumatic stress disorder (PTSD) is an anxiety disorder that can occur after exposure to extreme traumatic experience such as war trauma, and is accompanied by fear, helplessness or horror. Exposure to trauma can result in immune dysregulation and influence susceptibility to infectious disease as well as vaccine efficacy. The aim of the study was to determine the relation of psychological stress and the immune response to influenza vaccination in combat-related PTSD patients (n = 28). Detection of anti-viral antibody titre was performed by inhibition of haemagglutination assay. Ex vivo tetramer staining of CD8+ T lymphocytes was used to monitor T cells specific for human leucocyte antigen (HLA)-A*0201-restricted influenza A haemagglutinin antigens before and after vaccination. Twenty patients showed a fourfold antibody titre increase to one or both influenza A viral strains, and 18 of them showed the same response for both influenza B viral strains. Ten of 15 healthy controls showed a fourfold rise in antibody titre to both influenza A viral strains and eight of them showed the same response for both influenza B viral strains. HLA-A*0201+ PTSD patients (n = 10) showed a significant increase of influenza-specific CD8 T cells after vaccination. Although those PTSD patients had a lower number of influenza-specific CD8+ T cells before vaccination compared to HLA-A*0201+ healthy controls (n = 6), there was no difference in influenza A antibody titre between PTSD patients and control subjects before vaccination. The generated humoral and cellular immune response in PTSD patients argues against the hypothesis that combat-related PTSD in war veterans might affect protection following influenza vaccination. PMID:17511777

Introduction of Haemophilus influenzae type B conjugate vaccine into routine immunization in Ghana and its impact on bacterial meningitis in children younger than five years.

PubMed

Renner, Lorna Awo; Newman, Mercy J; Ahadzie, Lawson; Antwi-Agyei, Kwadwo Odei; Eshetu, Messeret

2007-04-01

This report shows the impact of a pentavalent vaccine that includes Haemophilus influenzae type b (Hib) conjugate vaccine on bacterial meningitis in children younger than 5 years in Ghana. A review of the first 3 years of a pediatric bacterial meningitis surveillance program, started in August 2001 in Accra, Ghana, was undertaken. There was a significant reduction, P = 0.042 and 0.017, in percentage of purulent meningitis in children younger than 1 year, comparing the first year when the vaccine was introduced, to the second and third years, respectively.

[Evaluation of immunogenicity and safety of 2 immunizations with allantoic intranasal live influenza vaccine Ultragrivac].

PubMed

Shishkina, L N; Mazurkova, N A; Ternovoĭ, V A; Bulychev, L E; Tumanov, Iu V; Skarnovich, M O; Kabanov, A S; Ryndiuk, N N; Kuzubov, V I; Mironov, A N; Stavskiĭ, E A; Drozdov, I G

2011-01-01

Evaluate reactogenicity, safety and immunogenicity in phase 2 clinical trials of 2 immunization schedules with Ultragrivac--an allantoic intranasal life influenza vaccine based on A/17/ duck/Potsdam/86/92 [17/H5] reassortant strain. 4 groups of volunteers participated in the study: group 1--40 individuals were vaccinated twice with a 10 day interval; group 2--40 individuals were vaccinated twice with a 21 day interval; group 3 (control)--10 individuals received placebo twice with a 10 day interval; group 4 (control)--10 individuals received placebo twice with a 21 day interval. Local (secretory IgA), cellular and humoral immune response were evaluated. Humoral immunity was evaluated by the intensity of increase of geometric mean antibody titers against 2 influenza virus strains A/17/duck/Potsdam/86/92 [17/H5] and A/chicken/Suzdalka/Nov-1 1/2005 (H5N1), and by the level of significant (4 times or more) antibody seroconversions after the vaccination. After the use of Ultragrivac the level of secretory IgA in the nasal cavity of vaccinated volunteers in the groups with revaccination intervals of 10 and 21 days increased significantly. The second immunization with 10 or 21 day intervals significantly increased postvaccinal humoral immune response. Humoral immune response induction after 2 vaccinations with 10 day interval was no less effective than with 21 day interval. Ultragrivac allantoic intranasal live influenza vaccine is areactogenic, harmless for vaccinated individuals, safe for those around, and has immunogenic properties against not only homologous virus A(H5N2), but also against influenza strain A(H5N1).

The Contribution of Systemic and Pulmonary Immune Effectors to Vaccine-Induced Protection from H5N1 Influenza Virus Infection

PubMed Central

Lau, Yuk-Fai; Wright, Amber R.

2012-01-01

Live attenuated influenza vaccines (LAIVs) are effective in providing protection against influenza challenge in animal models and in preventing disease in humans. We previously showed that LAIVs elicit a range of immune effectors and that successful induction of pulmonary cellular and humoral immunity in mice requires pulmonary replication of the vaccine virus. An upper respiratory tract immunization (URTI) model was developed in mice to mimic the human situation, in which the vaccine virus does not replicate in the lower respiratory tract, allowing us to assess the protective efficacy of an H5N1 LAIV against highly pathogenic H5N1 virus challenge in the absence of significant pulmonary immunity. Our results show that, after one dose of an H5N1 LAIV, pulmonary influenza-specific lymphocytes are the main contributors to clearance of challenge virus from the lungs and that contributions of influenza-specific enzyme-linked immunosorbent assay (ELISA) antibodies in serum and splenic CD8+ T cells were negligible. Complete protection from H5N1 challenge was achieved after two doses of H5N1 LAIV and was associated with maturation of the antibody response. Although passive transfer of sera from mice that received two doses of vaccine prevented lethality in naive recipients following challenge, the mice showed significant weight loss, with high pulmonary titers of the H5N1 virus. These data highlight the importance of mucosal immunity in mediating optimal protection against H5N1 infection. Understanding the requirements for effective induction and establishment of these protective immune effectors in the respiratory tract paves the way for a more rational and effective vaccine approach in the future. PMID:22379093

[THE COMPARATIVE ANALYSIS OF EFFECTIVENESS OF QUICK TESTS IN DIAGNOSTIC OF INFLUENZA AND RESPIRATORY SYNCYTIAL VIRAL INFECTION IN CHILDREN].

PubMed

Petrova, E R; Sukhovetskaia, V P; Pisareva, M M; Maiorova, V G; Sverlova, M V; Danilenko, D M; Petrova, P A; Krivitskaia, V Z; Sominina, A A

2015-11-01

The analysis was implemented concerning diagnostic parameters of commercial quick tests (immune chromatographic tests BinaxNOW Influenza A&B and BinaxNow RSV Alere, Scarborough Inc., USA) under detection of antigens of influenza virus A and respiratory syncytial virus in clinical materials. The polymerase chain reaction in real-time and isolation ofviruses in cell cultures. The analysis of naso-pharyngeal smears from 116 children demonstrated that sensitivity and specifcity of detection of influenza virus A using device mariPOC in comparison with polymerase chain reaction made up to 93.8% and 99.0% correspondingly at total concordance of results of both techniques as 98.3%. At diagnosing of respiratory syncytial virus using device mariPOC parameters made up to 77.3%, 98.9% and 862% as compared with polymerase chain reaction. The sensitivity, specificity and total concordance of results of immune chromatographic tests BinaxNOW in comparison ofpolymerase chain reaction made up to 86.7%, 100% and 96.2% correspondingly at detection of influenza virus A and 80.9%, 97.4% and 91.6% correspondingly at detection of respiratory syncytial virus. In comparison with isolation technique in cell cultures sensitivity of system mariPOC and immune chromatographic tests proved to be in 1.3-1.4 times higher at detection of influenza virus A and in 1.7-2 times higher in case of isolation of respiratory syncytial virus. There is no statistically significant differences between diagnostic parameters received for mariPOC and immune chromatographic tests at diagnosing influenza virus A and respiratory syncytial viral infection.

Immunogenicity and sustainability of the immune response in Brazilian HIV-1-infected individuals vaccinated with inactivated triple influenza vaccine.

PubMed

Souza, Thiago Moreno L; Santini-Oliveira, Marilia; Martorelli, Andressa; Luz, Paula M; Vasconcellos, Mauricio T L; Giacoia-Gripp, Carmem B W; Morgado, Mariza; Nunes, Estevão P; Lemos, Alberto S; Ferreira, Ana C G; Moreira, Ronaldo I; Veloso, Valdiléa G; Siqueira, Marilda; Grinsztejn, Beatriz; Camacho, Luiz A B

2016-03-01

HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination. © 2015 Wiley Periodicals, Inc.

Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model.

PubMed

Lee, Tae-Young; Kim, Chang-Ung; Bae, Eun-Hye; Seo, Sang-Hwan; Jeong, Dae Gwin; Yoon, Sun-Woo; Chang, Kyu-Tae; Kim, Young Sang; Kim, Sang-Hyun; Kim, Doo-Jin

2017-01-23

Influenza is an acute respiratory disease and a major health problem worldwide. Since mucosal immunity plays a critical role in protection against influenza virus infection, mucosal immunization is considered a promising vaccination route. However, except for live-attenuated vaccines, there are no effective killed or recombinant mucosal influenza vaccines to date. Outer membrane vesicles (OMVs) are nano-sized vesicles produced by gram-negative bacteria, and contain various bacterial components capable of stimulating the immune system of the host. We generated an OMV with low endotoxicity (fmOMV) by modifying the structure of the lipid A moiety of lipopolysaccharide and investigated its effect as an intranasal vaccine adjuvant in an influenza vaccine model. In this model, fmOMV exhibited reduced toll-like receptor 4-stimulating activity and attenuated endotoxicity compared to that of native OMV. Intranasal injection of the vaccine antigen with fmOMV significantly increased systemic antibody and T cell responses, mucosal IgA levels, and the frequency of lung-resident influenza-specific T cells. In addition, the number of antigen-bearing CD103 + dendritic cells in the mediastinal lymph nodes was significantly increased after fmOMV co-administration. Notably, the mice co-immunized with fmOMV showed a significantly higher protection rate against challenge with a lethal dose of homologous or heterologous influenza viruses without adverse effects. These results show the potential of fmOMV as an effective mucosal adjuvant for intranasal vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

Strategies to alleviate original antigenic sin responses to influenza viruses.

PubMed

Kim, Jin Hyang; Davis, William G; Sambhara, Suryaprakash; Jacob, Joshy

2012-08-21

Original antigenic sin is a phenomenon wherein sequential exposure to closely related influenza virus variants reduces antibody (Ab) response to novel antigenic determinants in the second strain and, consequently, impairs the development of immune memory. This could pose a risk to the development of immune memory in persons previously infected with or vaccinated against influenza. Here, we explored strategies to overcome original antigenic sin responses in mice sequentially exposed to two closely related hemagglutinin 1 neuraminidase 1 (H1N1) influenza strains A/PR/8/34 and A/FM/1/47. We found that dendritic cell-activating adjuvants [Bordetella pertussis toxin (PT) or CpG ODN or a squalene-based oil-in-water nanoemulsion (NE)], upon administration during the second viral exposure, completely protected mice from a lethal challenge and enhanced neutralizing-Ab titers against the second virus. Interestingly, PT and NE adjuvants when administered during the first immunization even prevented original antigenic sin in subsequent immunization without any adjuvants. As an alternative to using adjuvants, we also found that repeated immunization with the second viral strain relieved the effects of original antigenic sin. Taken together, our studies provide at least three ways of overcoming original antigenic sin.

Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

PubMed Central

Wu, Yuet; Lam, Kwok-Tai; Chow, Kin-Hung; Ho, Pak-Leung; Guan, Yi; Peiris, Joseph S. Malik

2014-01-01

ABSTRACT Secondary Streptococcus pneumoniae infection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. In the lung, lethal coinfection significantly increased virus titers and bacterial cell counts and decreased the level of virus-specific IgG, IgM, and IgA, as well as the number of B cells, CD4 T cells, and plasma cells. Lethal coinfection significantly reduced the size and weight of spleen, as well as the number of B cells along the follicular developmental lineage. In mediastinal lymph nodes, lethal coinfection significantly decreased germinal center B cells, T follicular helper cells, and plasma cells. Adoptive transfer of influenza virus-specific immune serum to coinfected mice improved survival, suggesting the protective functions of anti-influenza virus antibodies. In conclusion, coinfection reduced the B cell response to influenza virus. This study helps us to understand the modulation of the B cell response to influenza virus during a lethal coinfection. IMPORTANCE Secondary pneumococcal infection after influenza virus infection is an important clinical issue that often results in excess mortality. Since antibodies are key mediators of protection, this study aims to examine the antibody response to influenza virus and demonstrates that lethal coinfection reduced the B cell response to influenza virus. This study helps to highlight the complexity of the modulation of the B cell response in the context of coinfection. PMID:25428873

Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae

PubMed Central

Finney, Lydia J; Ritchie, Andrew; Pollard, Elizabeth; Johnston, Sebastian L; Mallia, Patrick

2014-01-01

Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans. PMID:25342897

Double-blind, randomized study of the effects of influenza vaccination on the specific antibody response and clinical course of patients with chronic fatigue syndrome

PubMed Central

Sleigh, Kenna M; Danforth, Donelda G; Hall, Raymond T; Fleming, Jonathan A; Stiver, H Grant

2000-01-01

OBJECTIVE: To determine whether influenza immunization is associated with early side effects, a deleterious impact on the illness course and depressed antibody response in patients with chronic fatigue syndrome (CFS). DESIGN: Prospective, randomized, double-blind, placebo controlled trial. CFS patients and healthy volunteers filled out a questionnaire on immunization side effects and had hemagglutination-inhibiting (HI) antibody titres measured pre- and three weeks after immunization. CFS patients completed symptom and function questionnaires before and during the six-week, postimmunization period. SETTING: Ambulatory care. POPULATION STUDIED: Convenience sample of 40 CFS patients fulfilling the Centers for Disease Control and Prevention criteria and 21 demographically matched healthy volunteers. INTERVENTIONS: CFS patients were randomly selected to receive commercially available whole virus influenza vaccine (n=19) or an injection of saline placebo (n=21). Healthy volunteers received vaccine only. MAIN RESULTS: As a group, immunized CFS patients had lower geometric mean HI antibody rises than healthy volunteers (P<0.001). However, there was no difference in the rates of fourfold titre rises, and immunization did achieve a probably protective titre (1:32 or greater) in most CFS patients. No difference could be detected between immunized and placebo CFS patients in immunization side effects, although CFS patients as a group reported four times as many side effects as healthy volunteers. Further, in the six weeks following immunization, placebo and immunized CFS patients did not demonstrate any differences in terms of functioning, symptom severity and sleep disturbance. CONCLUSIONS: In patients with CFS, influenza immunization is safe, not associated with any excess early reactions, and stimulates an immunizing response comparable with that of healthy volunteers. PMID:18159300

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

PubMed Central

Seong, Yekyung; Lazarus, Nicole H.; Sutherland, Lusijah; Habtezion, Aida; Abramson, Tzvia; He, Xiao-Song; Greenberg, Harry B.

2017-01-01

Antibody-secreting cells are generated in regional lymphoid tissues and traffic as plasmablasts (PBs) via lymph and blood to target sites for local immunity. We used multiparameter flow cytometry to define PB trafficking programs (TPs, combinations of adhesion molecules and chemoattractant receptors) and their imprinting in patients in response to localized infection or immune insults. TPs enriched after infection or autoimmune inflammation of mucosae correlate with sites of immune response or symptoms, with different TPs imprinted during small intestinal, colon, throat, and upper respiratory immune challenge. PBs induced after intramuscular or intradermal influenza vaccination, including flu-specific antibody–secreting cells, display TPs characterized by the lack of mucosal homing receptors. PBs of healthy donors display diverse mucosa-associated TPs, consistent with homeostatic immune activity. Identification of TP signatures of PBs may facilitate noninvasive monitoring of organ-specific immune responses. PMID:28352656

Focusing on flu

PubMed Central

Short, Mary B; Middleman, Amy B

2014-01-01

Introduction: To describe adolescents' perspectives regarding the use of school-located immunization programs (SLIP) for influenza vaccination. More importantly, adolescents were asked what factors would make them more or less likely to use a SLIP offering influenza vaccine. Results: Participants were generally found to be knowledgeable about influenza and to have positive attitudes toward receiving the vaccine via SLIP. Students were more willing to participate in a SLIP if it were low cost or free, less time-consuming than going to a doctor, and if they felt they could trust vaccinators. Overall, high school and middle school students ranked the benefits of SLIP similarly to each other. Methods: Focus groups using nominal group method were conducted with middle and high school students in a large, urban school district. Responses were recorded by each school, and then, responses were ranked across all participating schools for each question. Conclusions: A wide range of issues are important to middle and high school students when considering participation in SLIPs including convenience, public health benefits, trust in the program, program safety, and sanitary issues. Further research will be needed regarding the generalizability of these findings to larger populations of students. PMID:24018398

Cellular and humoral cross-immunity against two H3N2v influenza strains in presumably unexposed healthy and HIV-infected subjects.

PubMed

Agrati, Chiara; Castilletti, Concetta; Cimini, Eleonora; Lapa, Daniele; Quartu, Serena; Caglioti, Claudia; Lanini, Simone; Cattoli, Giovanni; Martini, Federico; Ippolito, Giuseppe; Capobianchi, Maria R

2014-01-01

Human cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States. Pre-existing humoral and cellular immunity has been recognized as one of the key factors in limiting the infection burden of an emerging influenza virus strain, contributing to restrict its circulation and to mitigate clinical presentation. Aim of this study was to assess humoral and cell-mediated cross immune responses to H3N2v in immuno-competent (healthy donors, n = 45) and immuno-compromised hosts (HIV-infected subjects, n = 46) never exposed to H3N2v influenza strain. Humoral response against i) H3N2v (A/H3N2/Ind/08/11), ii) animal vaccine H3N2 strain (A/H3N2/Min/11/10), and iii) pandemic H1N1 virus (A/H1N1/Cal/07/09) was analysed by hemagglutination inhibition assay; cell-mediated response against the same influenza strains was analysed by ELISpot assay. A large proportion of healthy and HIV subjects displayed cross-reacting humoral and cellular immune responses against two H3N2v strains, suggesting the presence of B- and T-cell clones able to recognize epitopes from emerging viral strains in both groups. Specifically, humoral response was lower in HIV subjects than in HD, and a specific age-related pattern of antibody response against different influenza strains was observed both in HD and in HIV. Cellular immune response was similar between HD and HIV groups and no relationship with age was reported. Finally, no correlation between humoral and cellular immune response was observed. Overall, a high prevalence of HD and HIV patients showing cross reactive immunity against two H3N2v strains was observed, with a slightly lower proportion in HIV persons. Other studies focused on HIV subjects at different stages of diseases are needed in order to define how cross immunity can be affected by advanced immunosuppression.

Antigen-activated dendritic cells ameliorate influenza A infections

PubMed Central

Boonnak, Kobporn; Vogel, Leatrice; Orandle, Marlene; Zimmerman, Daniel; Talor, Eyal; Subbarao, Kanta

2013-01-01

Influenza A viruses cause significant morbidity and mortality worldwide. There is a need for alternative or adjunct therapies, as resistance to currently used antiviral drugs is emerging rapidly. We tested ligand epitope antigen presentation system (LEAPS) technology as a new immune-based treatment for influenza virus infection in a mouse model. Influenza-J-LEAPS peptides were synthesized by conjugating the binding ligand derived from the β2-microglobulin chain of the human MHC class I molecule (J-LEAPS) with 15 to 30 amino acid–long peptides derived from influenza virus NP, M, or HA proteins. DCs were stimulated with influenza-J-LEAPS peptides (influenza-J-LEAPS) and injected intravenously into infected mice. Antigen-specific LEAPS-stimulated DCs were effective in reducing influenza virus replication in the lungs and enhancing survival of infected animals. Additionally, they augmented influenza-specific T cell responses in the lungs and reduced the severity of disease by limiting excessive cytokine responses, which are known to contribute to morbidity and mortality following influenza virus infection. Our data demonstrate that influenza-J-LEAPS–pulsed DCs reduce virus replication in the lungs, enhance survival, and modulate the protective immune responses that eliminate the virus while preventing excessive cytokines that could injure the host. This approach shows promise as an adjunct to antiviral treatment of influenza virus infections. PMID:23934125

Conventional influenza vaccines influence the performance of a universal influenza vaccine in mice.

PubMed

Rowell, Janelle; Lo, Chia-Yun; Price, Graeme E; Misplon, Julia A; Epstein, Suzanne L; Garcia, Mayra

2018-02-08

Universal influenza vaccines are designed to protect against diverse strains of influenza virus. Preclinical testing of new vaccine candidates is usually done in naïve animals, despite intended use in the human population with its varied immune history including responses to previous vaccinations. As an approach more relevant to human use, we tested a candidate universal influenza vaccine in mice with a history of conventional vaccination. Female BALB/c mice were given two intramuscular doses of inactivated influenza vaccine (IIV) or diphtheria and tetanus toxoids vaccine (DT), one month apart. Another group was given two intranasal doses of live attenuated influenza virus (LAIV). One month after the second dose, mice were given the universal influenza vaccine: recombinant adenoviruses expressing influenza A nucleoprotein (A/NP) and matrix 2 (M2) (A/NP + M2-rAd). Immune responses to universal vaccine antigens A/NP and M2 were assessed by ELISA and interferon-γ ELISPOT. Protection was tested by challenge with mouse-adapted A/FM/1/47 (H1N1) and monitoring for weight loss and survival. Universal vaccine performance was enhanced, inhibited or unaffected by particular prior vaccinations. Mice given Afluria IIV and LAIV had greater antibody and T-cell response to A/NP than mice without prior vaccination, providing examples of enhanced A/NP + M2-rAd performance. Though Fluvirin IIV partially inhibited, the universal vaccine still provided considerable protection unlike conventional vaccination. Fluzone IIV and DT had no effect on A/NP + M2-rAd performance. Thus our results demonstrate that universal vaccine candidate A/NP + M2-rAd was at least partially effective in mice with diverse prior histories. However, the degree of protection and nature of the immune responses may be affected by a history of conventional vaccination and suggests that performance in humans would be influenced by immune history. Published by Elsevier Ltd.

Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raymond, Donald D.; Bajic, Goran; Ferdman, Jack

Antigenic variation requires frequent revision of annual influenza vaccines. Next-generation vaccine design strategies aim to elicit a broader immunity by directing the human immune response toward conserved sites on the principal viral surface protein, the hemagglutinin (HA). We describe a group of antibodies that recognize a hitherto unappreciated, conserved site on the HA of H1 subtype influenza viruses. Mutations in that site, which required a change in the H1 component of the 2017 vaccine, had not previously “taken over” among circulating H1 viruses. Our results encourage vaccine design strategies that resurface a protein to focus the immune response on amore » specific region.« less

THE ANTIGENIC POTENCY OF EPIDEMIC INFLUENZA VIRUS FOLLOWING INACTIVATION BY ULTRAVIOLET RADIATION

PubMed Central

Salk, Jonas E.; Lavin, G. I.; Francis, Thomas

1940-01-01

A study of the antigenic potency of influenza virus inactivated by ultraviolet radiation has been made. Virus so inactivated is still capable of functioning as an immunizing agent when given to mice by the intraperitoneal route. In high concentrations inactivated virus appears to be nearly as effective as active virus but when quantitative comparisons of the immunity induced by different dilutions are made, it is seen that a hundredfold loss in immunizing capacity occurs during inactivation. Virus in suspensions prepared from the lungs of infected mice is inactivated more rapidly than virus in tissue culture medium. A standard for the comparison of vaccines of epidemic influenza virus is proposed. PMID:19871057

Endocrine regulation of the immune response to influenza virus infection with a metabolite of DHEA-androstenediol.

PubMed

Padgett, D A; Loria, R M; Sheridan, J F

1997-09-01

In these studies the influence of androstenediol on the course of an experimental virus infection was examined. Pretreatment with 320 mg/kg AED protected male mice from lethal influenza virus infection. In addition, AED enhanced antigen-induced trafficking of mononuclear cells into the draining lymph node and augmented antigen-specific activation of helper-T cells, which are important for control of viral pathogenesis. Furthermore, AED prevented the characteristic increase in serum corticosterone noted during influenza A virus infection. Although steroid hormones, at least corticosteroids, typically suppress host immune and inflammatory responses in vivo, these data suggest that AED may function to augment host immune and inflammatory responses in contrast to corticosteroids.

A comprehensive influenza campaign in a managed care setting.

PubMed

Pearson, D C; Jackson, L A; Wagener, B; Sarver, L

1998-11-01

Group Health Cooperative, a large, membership-governed, staff model health maintenance organization (HMO), has designed a comprehensive influenza campaign for identifying, recruiting and vaccinating enrollees at increased risk for influenza-related complications. The Cooperative's Centre for Health Promotion is responsible for the overall planning, implementation and evaluation of the influenza campaign. The model for delivering influenza immunizations has been designed to build on the strengths and capabilities of a staff model HMO with sophisticated automated information systems. The model permits area medical centres (AMCs) and physicians to use the materials and intervention strategies generated by the Centre for Health Promotion, while at the same time allowing them flexibility to design and use their own intervention strategies to increase compliance. More importantly, the model reduces resource requirements on AMCs and physicians to plan and maintain internal immunization efforts. Recommendations for improving the influenza campaign are discussed.

Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity

PubMed Central

Wang, Zhongfang; Loh, Liyen; Kedzierski, Lukasz; Kedzierska, Katherine

2016-01-01

Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and 35%, respectively. Ongoing circulation of H5N1 and H7N9 viruses in wild birds and poultry, and their ability to infect humans emphasizes their epidemic and pandemic potential and poses a public health threat. It is, thus, imperative to understand the host immune responses to the AIVs so we can control severe influenza disease caused by H5N1 or H7N9 and rationally design new immunotherapies and vaccines. This review summarizes our current knowledge on AIV epidemiology, disease symptoms, inflammatory processes underlying the AIV infection in humans, and recent studies on universal pre-existing CD8+ T cell immunity to AIVs. Immune responses driving the host recovery from AIV infection in patients hospitalized with severe influenza disease are also discussed. PMID:26973644

Healthcare Professionals' Knowledge of Influenza and Influenza Vaccination: Results of a National Survey in Poland.

PubMed

Kuchar, Ernest; Ludwikowska, Kamila; Antczak, Adam; Nitsch-Osuch, Aneta

2018-01-01

In Poland, the seasonal influenza vaccination rate is just barely 3% which may be related to the unsatisfactory knowledge of influenza among healthcare professionals, poor recognition of the benefits of influenza immunization and the fear of side effects. To address these issues, we surveyed healthcare professionals through an online questionnaire consisting of 18 closed-ended items. The questionnaire was completed by 495 healthcare professionals, mostly physicians (83%). The results revealed gaps in the knowledge concerning influenza diagnosis, complications, risk groups, and prognostic factors. On average, respondents only answered 4.8 of the 18 questions correctly (27%). Only 10% of respondents passed the threshold of 50% correct answers. The knowledge of contraindications to vaccination far outweighed the knowledge of indications for vaccination. Poor knowledge with a focus on the adverse effects of immunization may be a significant factor responsible for the low vaccination rate in Poland. To increase vaccination rate, healthcare professionals need to be educated about influenza-related risks and benefits of vaccination.

Adaptive heterosubtypic immunity to low pathogenic avian influenza viruses in experimentally infected mallards

USDA-ARS?s Scientific Manuscript database

Mallards are widely recognized as reservoirs for Influenza A viruses (IAV), however host factors that might prompt seasonality and trends in subtype diversity of IAV such as adaptive heterosubtypic immunity (HSI) are not well understood. We inoculated mallards with a prevailing H3N8 low pathogenic a...

Cross reactive immunity derived from chickens infected with H9N2 low pathogenic avian influenza against homologous and heterosubtypic challenge

USDA-ARS?s Scientific Manuscript database

Because vaccines for use in commercial poultry against avian influenza (AI) are mainly inactivated and delivered parenterally, our knowledge of protective immunity of poultry against AI is largely based on the induction of serum-neutralizing antibodies produced against a specific hemagglutinin (HA) ...

Vaccine-critical videos on YouTube and their impact on medical students' attitudes about seasonal influenza immunization: a pre and post study.

PubMed

Robichaud, Pierre; Hawken, Steven; Beard, Leslie; Morra, Dante; Tomlinson, George; Wilson, Kumanan; Keelan, Jennifer

2012-05-28

YouTube is a video-sharing platform that is increasingly utilized to share and disseminate health-related information about immunization. Using a pre-post survey methodology, we compared the impact of two of the most popular YouTube videos discussing seasonal influenza vaccine, both vaccine-critical, on the attitudes towards immunizing of first year medical students attending a Canadian medical school. Forty-one medical students were randomized to view either a scientifically styled, seemingly "evidence-based", vaccine-critical video or a video using anecdotal stories of harms and highly sensationalized imagery. In the pre-intervention survey, medical students frequently used YouTube for all-purposes, while 42% used YouTube for health-related purposes and 12% used YouTube to search for health information. While medical students were generally supportive of immunizing, there was suboptimal uptake of annual influenza vaccine reported, and a subset of our study population expressed vaccine-critical attitudes and behaviors with respect to seasonal influenza. Overall there was no significant difference in pre to post attitudes towards influenza immunization nor were there any differences when comparing the two different vaccine-critical videos. The results of our study are reassuring in that they suggest that medical students are relatively resistant to the predominately inaccurate, vaccine-critical messaging on YouTube, even when the message is framed as scientific reasoning. Further empirical work is required to test the popular notion that information disseminated through social media platforms influences health-related attitudes and behaviors. However, our study suggests that there is an opportunity for public health to leverage YouTube to communicate accurate and credible information regarding influenza to medical students and others. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lack of effect of a booster dose of influenza vaccine in hemodialysis patients.

PubMed

Tanzi, Elisabetta; Amendola, Antonella; Pariani, Elena; Zappa, Alessandra; Colzani, Daniela; Logias, Franco; Perego, Angelo; Zanetti, Alessandro R

2007-08-01

To assess whether the administration of a booster dose of influenza vaccine may enhance immune response in hemodialysis patients, 58 subjects were given two doses of the 2003/2004 season influenza vaccine, 1 month apart. "European Agency for the Evaluation of Medicinal Products" (EMEA) criteria were fully met in terms of percentage of response and of mean-fold increase of hemagglutination inhibiting (HI) antibody titer, but not in terms of seroprotection rates (HI antibody titers > or =1:40). The second vaccine administration did not result in additional increase in seroprotection rate or in geometric mean titers. Protective immune response against the epidemic A/H3N2 Fujian-like strain, antigenically distant from that included in the vaccine (A/Panama/2007/99) was observed in 94.7% of vaccinees protected against the A/H3N2 vaccine strain 1 month after immunization. No adverse reactions were reported during follow-up. The study findings suggest that immune response to influenza vaccination may be suboptimal in hemodialysis patients and that the administration of an additional second dose of vaccine does not improve the humoral response.

[AVIAN RECOMBINANT VIRUS H5N1 INFLUENZA (A/VIETNAM/1203/04) AND ITS ESCAPE-MUTANT m13(13) INDUCE EARLY SIGNALING REACTIONS OF THE IMMUNITY IN HUMAN LYMPHOCYTES].

PubMed

Sokolova, T M; Poloskov, V V; Shuvalov, A N; Rudneva, I A; Ershov, F I

2016-01-01

The innate immune receptors TLR4, TLR7, TLR8, and RIG1 recognized the structures of the influenza viruses in human lymphocytes and were activated by the recombinant avian influenza virus A/Vietnam/1203/04 and its escape-mutant m13(13) during early period of interaction. The stimulated levels are not connected with viral reproduction. Donor cells with the low constitutive immune receptors gene expression levels showed higher stimulation. Inflammation virus effects resulted in. increasing production of TNF-alpha and IFN-gamma by lymphocytes. Signaling gene reactions of the parent and mutant viruses endosomal as well as cytoplasmic receptors are very similar. The mutant virus A/Vietnam/1203/04 (HA S145F), stimulated an increase in the transcription level of the membrane receptor gene TLR4 and a decrease in the level of activation of TNF-alpha gene. Further studies of natural influenza virus isolates are necessary to estimate the role of HA antigenic changes on immune reactions in humans.

Enhanced Influenza Virus-Like Particle Vaccination with a Structurally Optimized RIG-I Agonist as Adjuvant.

PubMed

Beljanski, Vladimir; Chiang, Cindy; Kirchenbaum, Greg A; Olagnier, David; Bloom, Chalise E; Wong, Terianne; Haddad, Elias K; Trautmann, Lydie; Ross, Ted M; Hiscott, John

2015-10-01

The molecular interaction between viral RNA and the cytosolic sensor RIG-I represents the initial trigger in the development of an effective immune response against infection with RNA viruses, resulting in innate immune activation and subsequent induction of adaptive responses. In the present study, the adjuvant properties of a sequence-optimized 5'-triphosphate-containing RNA (5'pppRNA) RIG-I agonist (termed M8) were examined in combination with influenza virus-like particles (VLP) (M8-VLP) expressing H5N1 influenza virus hemagglutinin (HA) and neuraminidase (NA) as immunogens. In combination with VLP, M8 increased the antibody response to VLP immunization, provided VLP antigen sparing, and protected mice from a lethal challenge with H5N1 influenza virus. M8-VLP immunization also led to long-term protective responses against influenza virus infection in mice. M8 adjuvantation of VLP increased endpoint and antibody titers and inhibited influenza virus replication in lungs compared with approved or experimental adjuvants alum, AddaVax, and poly(I·C). Uniquely, immunization with M8-VLP stimulated a TH1-biased CD4 T cell response, as determined by increased TH1 cytokine levels in CD4 T cells and increased IgG2 levels in sera. Collectively, these data demonstrate that a sequence-optimized, RIG-I-specific agonist is a potent adjuvant that can be utilized to increase the efficacy of influenza VLP vaccination and dramatically improve humoral and cellular mediated protective responses against influenza virus challenge. The development of novel adjuvants to increase vaccine immunogenicity is an important goal that seeks to improve vaccine efficacy and ultimately prevent infections that endanger human health. This proof-of-principle study investigated the adjuvant properties of a sequence-optimized 5'pppRNA agonist (M8) with enhanced capacity to stimulate antiviral and inflammatory gene networks using influenza virus-like particles (VLP) expressing HA and NA as immunogens. Vaccination with VLP in combination with M8 increased anti-influenza virus antibody titers and protected animals from lethal influenza virus challenge, highlighting the potential clinical use of M8 as an adjuvant in vaccine development. Altogether, the results describe a novel immunostimulatory agonist targeted to the cytosolic RIG-I sensor as an attractive vaccine adjuvant candidate that can be used to increase vaccine efficacy, a pressing issue in children and the elderly population. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effect of the conditional cash transfer program Oportunidades on vaccination coverage in older Mexican people.

PubMed

Salinas-Rodríguez, Aarón; Manrique-Espinoza, Betty Soledad

2013-07-08

Immunization is one of the most effective ways of preventing illness, disability and death from infectious diseases for older people. However, worldwide immunization rates are still low, particularly for the most vulnerable groups within the elderly population. The objective of this study was to estimate the effect of the Oportunidades -an incentive-based poverty alleviation program- on vaccination coverage for poor and rural older people in Mexico. Cross-sectional study, based on 2007 Oportunidades Evaluation Survey, conducted in low-income households from 741 rural communities (localities with <2,500 inhabitants) of 13 Mexican states. Vaccination coverage was defined according to three individual vaccines: tetanus, influenza and pneumococcal, and for complete vaccination schedule. Propensity score matching and linear probability model were used in order to estimate the Oportunidades effect. 12,146 older people were interviewed, and 7% presented cognitive impairment. Among remaining, 4,628 were matched. Low coverage rates were observed for the vaccines analyzed. For Oportunidades and non-Oportunidades populations were 46% and 41% for influenza, 52% and 45% for pneumococcal disease, and 79% and 71% for tetanus, respectively. Oportunidades effect was significant in increasing the proportion of older people vaccinated: for complete schedule 5.5% (CI95% 2.8-8.3), for influenza 6.9% (CI95% 3.8-9.6), for pneumococcal 7.2% (CI95% 4.3-10.2), and for tetanus 6.6% (CI95% 4.1-9.2). The results of this study extend the evidence on the effect that conditional transfer programs exert on health indicators. In particular, Oportunidades increased vaccination rates in the population of older people. There is a need to continue raising vaccination rates, however, particularly for the most vulnerable older people.

Effect of the conditional cash transfer program Oportunidades on vaccination coverage in older Mexican people

PubMed Central

2013-01-01

Background Immunization is one of the most effective ways of preventing illness, disability and death from infectious diseases for older people. However, worldwide immunization rates are still low, particularly for the most vulnerable groups within the elderly population. The objective of this study was to estimate the effect of the Oportunidades -an incentive-based poverty alleviation program- on vaccination coverage for poor and rural older people in Mexico. Methods Cross-sectional study, based on 2007 Oportunidades Evaluation Survey, conducted in low-income households from 741 rural communities (localities with <2,500 inhabitants) of 13 Mexican states. Vaccination coverage was defined according to three individual vaccines: tetanus, influenza and pneumococcal, and for complete vaccination schedule. Propensity score matching and linear probability model were used in order to estimate the Oportunidades effect. Results 12,146 older people were interviewed, and 7% presented cognitive impairment. Among remaining, 4,628 were matched. Low coverage rates were observed for the vaccines analyzed. For Oportunidades and non-Oportunidades populations were 46% and 41% for influenza, 52% and 45% for pneumococcal disease, and 79% and 71% for tetanus, respectively. Oportunidades effect was significant in increasing the proportion of older people vaccinated: for complete schedule 5.5% (CI95% 2.8-8.3), for influenza 6.9% (CI95% 3.8-9.6), for pneumococcal 7.2% (CI95% 4.3-10.2), and for tetanus 6.6% (CI95% 4.1-9.2). Conclusions The results of this study extend the evidence on the effect that conditional transfer programs exert on health indicators. In particular, Oportunidades increased vaccination rates in the population of older people. There is a need to continue raising vaccination rates, however, particularly for the most vulnerable older people. PMID:23835202

Effectiveness of Haemophilus influenzae type b conjugate vaccine introduction into routine childhood immunization in Kenya

PubMed Central

Cowgill, Karen D.; Ndiritu, Moses; Nyiro, Joyce; Slack, Mary P. E.; Chiphatsi, Salome; Ismail, Amina; Kamau, Tatu; Mwangi, Isaiah; English, Mike; Newton, Charles R. J. C.; Feikin, Daniel R.; Scott, J. Anthony G.

2006-01-01

Context Haemophilus influenzae type b (Hib) conjugate vaccine is not perceived as a public health priority in Africa because data on Hib disease burden and vaccine effectiveness are scarce. Hib immunization was introduced in Kenyan infants in 2001. Objective to define invasive Hib disease incidence and Hib vaccine program effectiveness. Design, Setting, Patients culture-based surveillance for invasive Hib disease at Kilifi District Hospital from 2000 to 2005 was linked to demographic surveillance of 38,000 children aged <5 years in Kilifi District, Kenya. HIV infection and Hib vaccination status were determined for children with Hib disease admitted 2002–2005. Interventions Conjugate Hib vaccine within the routine childhood immunization program at ages 6, 10 and 14 weeks from November 2001 Main outcome measures Incidence of culture-proven Hib invasive disease before and after vaccine introduction and vaccine program effectiveness (1-incidence rate ratio) Results Prior to vaccine introduction the median age of Hib cases was 8 months; case fatality was 23%. Among children aged <5 years the annual incidence of invasive Hib disease 1 year before and 1 and 3 years after vaccine introduction was 66, 47 and 7.6 per 100,000, respectively. For children <2 years, incidence was 119, 82 and 16, respectively. In 2004–2005 vaccine effectiveness was 88% (95% CI 73–96%) among children <5 years and 87% (95% CI 66–96%) among children <2 years. Of 53 Hib cases admitted during 2002–2005, 29 (55%) were age-ineligible to have received vaccine, 12 (23%) had not been vaccinated despite being eligible, and 12 (23%) had received ≥2 doses of vaccine (2 were HIV-positive). Conclusions In Kenya, introduction of Hib vaccine into the routine childhood immunization program reduced Hib disease incidence among children aged <5 years to 12% of its baseline level. This impact was not observed until the third year after vaccine introduction. PMID:16896110

Towards a universal influenza vaccine: volunteer virus challenge studies in quarantine to speed the development and subsequent licensing.

PubMed

Oxford, John S

2013-08-01

There are now more than 5 experimental vaccine formulations which induce T and B cell immunity towards the internally situated virus proteins matrix (M1 and M2e) and nucleoprotein (NP), and towards stem and stalk regions of the HA which have a shared antigenic structure amongst many of the 17 influenza A virus sub types. Such 'universal vaccines' could be used, at least in theory, as a prophylactic stockpile vaccine for newly emerged epidemic and novel pandemic influenza A viruses or as a supplement to conventional HA/NA vaccines. My own laboratory has approached the problem from the clinical viewpoint by identifying CD4(+) cells which are present in influenza infected volunteers who resist influenza infection. We have established precisely which peptides in M and NP proteins react with these immune CD4 cells. These experimental vaccines induce immunity in animal models but with a single exception no data have been published on protection against influenza virus infection in humans. The efficacy of the latter vaccine is based on vaccinia virus (MVA) as a carrier and was analyzed in a quarantine unit. Given the absence of induced HI antibody in the new universal vaccines a possible licensing strategy is a virus challenge model in quarantine whereby healthy volunteers can be immunized with the new vaccine and thereafter deliberately infected and clinical signs recorded alongside quantities of virus excreted and compared with unvaccinated controls. © 2013 The British Pharmacological Society.

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses.

PubMed

Chen, Sujuan; Zhu, Yinbiao; Yang, Da; Yang, Yang; Shi, Shaohua; Qin, Tao; Peng, Daxin; Liu, Xiufan

2017-01-01

H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

Effect of Lactobacillus paracasei subsp. paracasei, L. casei 431 on immune response to influenza vaccination and upper respiratory tract infections in healthy adult volunteers: a randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Jespersen, Lillian; Tarnow, Inge; Eskesen, Dorte; Morberg, Cathrine Melsaether; Michelsen, Birgit; Bügel, Susanne; Dragsted, Lars Ove; Rijkers, Ger T; Calder, Philip C

2015-06-01

Probiotics can modulate the immune system in healthy individuals and may help reduce symptoms related to respiratory infections. The objective of the study was to investigate the effect of the probiotic strain Lactobacillus paracasei subsp. paracasei, L. casei 431 (Chr. Hansen A/S) (hereafter, L. casei 431) on immune response to influenza vaccination and respiratory symptoms in healthy adults. A randomized double-blind, placebo-controlled trial was conducted in 1104 healthy subjects aged 18-60 y at 2 centers in Germany and Denmark. Subjects were randomly assigned to receive an acidified milk drink containing ≥10(9) colony-forming units of L. casei 431 (n = 553) or placebo (n = 551) for 42 d. After 21 d, subjects received the seasonal influenza vaccination. The primary outcome was seroprotection rate (anti-influenza antibody titers by hemagglutination inhibition) 21 d after vaccination. Other outcomes were seroconversion rate and mean titers, influenza A-specific antibodies and incidence, and duration and severity of upper respiratory symptoms. Antibiotic use and use of health care resources were recorded. There was no effect of L. casei 431 on immune responses to influenza vaccination. Generalized linear mixed modeling showed a shorter duration of upper respiratory symptoms in the probiotic group than in the placebo group (mean ± SD: 6.4 ± 6.1 vs. 7.3 ± 9.7 d, P = 0.0059) in the last 3 wk of the intervention period. No statistically significant differences were found for incidence or severity. Daily consumption of L. casei 431 resulted in no observable effect on the components of the immune response to influenza vaccination but reduced the duration of upper respiratory symptoms. The trial was registered at www.isrctn.com as ISRCTN08280229. © 2015 American Society for Nutrition.

Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic

PubMed Central

Lo, Chia-Yun; Strobl, Susan L.; Dunham, Kimberly; Wang, Wei; Stewart, Lucy; Misplon, Julia A.; Garcia, Mayra; Gao, Jin; Ozawa, Tatsuhiko; Price, Graeme E.; Navidad, Jose; Gradus, Steve; Bhattacharyya, Sanjib; Viboud, Cecile; Eichelberger, Maryna C.; Weiss, Carol D.; Gorski, Jack

2017-01-01

Abstract Background. Antibody and T-cell immunity to conserved influenza virus antigens can protect animals against infection with diverse influenza strains. Although immunity against conserved antigens occurs in humans, whether such responses provide cross-protection in humans and could be harnessed as the basis for universal influenza vaccines is controversial. The 2009 pandemic provided an opportunity to investigate whether pre-existing cross-reactive immunity affected susceptibility to infection. Methods. In 2009, we banked sera and peripheral blood mononuclear cells (PBMC) from blood donors, then monitored them for pandemic influenza infection (pH1N1) by polymerase chain reaction or seroconversion. Antibodies to hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix 2 (M2), and HA-pseudotypes were measured in sera. T-cell inteferon-γ enzyme-linked immunospot responses were measured in PBMC. Results. There were 13 infections in 117 evaluable donors. Pre-existing T-cell reactivity to pH1N1 was substantial (of 153 donors tested, 146 had >100 spot-forming cells/106 cells). Antibodies reactive with pH1N1 were common: anti-NP (all donors) and anti-M2 (44% of donors). Pseudotype-neutralizing antibodies to H1 were detected, but not to highly conserved HA epitopes. Unexpectedly, donors with symptomatic pH1N1 infection had sharp rises in HA pseudotype-neutralizing antibodies, not only pH1N1 but also against multiple seasonal H1s. In addition, an exploratory study of a T-cell marker (response to NP418-426) identified probable infection missed by standard criteria. Conclusions. Although the number of infections was inadequate for conclusions about mechanisms of protection, this study documents the wide variety of pre-existing, cross-reactive, humoral and cellular immune responses to pandemic influenza virus antigens in humans. These responses can be compared with results of other studies and explored in universal influenza vaccine studies. PMID:28730155

Sialidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype.

PubMed

Walz, Lisa; Kays, Sarah-Katharina; Zimmer, Gert; von Messling, Veronika

2018-06-20

Immune responses induced by currently licensed inactivated influenza vaccines are mainly directed against the hemagglutinin (HA) glycoprotein, the immunodominant antigen of influenza viruses. The resulting antigenic drift of HA requires frequent updating of the vaccine composition and annual revaccination. On the other hand, the level of antibodies directed against the neuraminidase (NA) glycoprotein, the second major influenza virus antigen, vary greatly. To investigate the potential of the more conserved NA protein for the induction of a subtype-specific protection, vesicular stomatitis virus-based replicons expressing a panel of N1 proteins from prototypic seasonal and pandemic H1N1 strain and human H5N1 and H7N9 isolates were generated. Immunization of mice and ferrets with the replicon carrying the matched N1 protein resulted in robust humoral and cellular immune responses and protected against challenge with the homologous influenza virus with similar efficacy as the matched HA protein, illustrating the potential of the NA protein as vaccine antigen. The extent of protection after immunization with mismatched N1 proteins correlated with the level of cross-reactive sialidase-inhibiting antibody titers. Passive serum transfer experiments in mice confirmed that these functional antibodies determine subtype-specific cross-protection. Our findings illustrate the potential of NA-specific immunity for achieving broader protection against antigenic drift variants or newly emerging viruses carrying the same NA but a different HA subtype. IMPORTANCE Despite the availability of vaccines, annual influenza virus epidemics cause 250,000 to 500,000 deaths worldwide. Currently licensed inactivated vaccines, which are standardized for the amount of the hemagglutinin (HA) antigen, primarily induce strain-specific antibodies whereas the immune response to the neuraminidase (NA) antigen, which is also present on the viral surface, is usually low. Using NA-expressing single-cycle vesicular stomatitis virus replicons, we show that the NA antigen not only conferred protection of mice and ferrets to the matched influenza strains, but also against viruses carrying NA proteins from other strains of the same subtype. The extent of protection correlated with the level of cross-reactive NA-inhibiting antibodies. This highlights the potential of the NA antigen for the development of more broadly protective influenza vaccines. Such vaccines may also provide partial protection against newly emerging strains with the same NA but a different HA subtype. Copyright © 2018 American Society for Microbiology.

Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity.

PubMed

Wang, Bao-Zhong; Gill, Harvinder S; He, Cheng; Ou, Changbo; Wang, Li; Wang, Ying-Chun; Feng, Hao; Zhang, Han; Prausnitz, Mark R; Compans, Richard W

2014-03-28

Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the Toll-like receptor (TLR) 5-agonist domains from flagellin and multiple repeats of the conserved extracellular domain of the influenza matrix protein 2 (M2e) was constructed, purified and evaluated as such a vaccine. A painless vaccination method suitable for possible self-administration using coated microneedle arrays was investigated for skin-targeted delivery of the fusion protein in a mouse model. The results demonstrate that microneedle immunization induced strong humoral as well as mucosal antibody responses and conferred complete protection against homo- and heterosubtypic lethal virus challenges. Protective efficacy with microneedles was found to be significantly better than that seen with conventional intramuscular injection, and comparable to that observed with intranasal immunization. Because of its advantages for administration, safety and storage, microneedle delivery of M2e-flagellin fusion protein is a promising approach for an easy-to-administer universal influenza vaccine. Copyright © 2014 Elsevier B.V. All rights reserved.

T-cell-mediated cross-strain protective immunity elicited by prime-boost vaccination with a live attenuated influenza vaccine.

PubMed

Li, Junwei; Arévalo, Maria T; Chen, Yanping; Chen, Shan; Zeng, Mingtao

2014-10-01

Antigenic drift and shift of influenza viruses require frequent reformulation of influenza vaccines. In addition, seasonal influenza vaccines are often mismatched to the epidemic influenza strains. This stresses the need for a universal influenza vaccine. BALB/c mice were vaccinated with the trivalent live attenuated (LAIV; FluMist) or inactivated (TIV; FluZone) influenza vaccines and challenged with PR8 (H1N1), FM/47 (H1N1), or HK/68 (H3N2) influenza virus. Cytokines and antibody responses were tested by ELISA. Furthermore, different LAIV dosages were applied in BALB/c mice. LAIV vaccinated mice were also depleted of T-cells and challenged with PR8 virus. LAIV induced significant protection against challenge with the non-vaccine strain PR8 influenza virus. Furthermore, protective immunity against PR8 was dose-dependent. Of note, interleukin 2 and interferon gamma cytokine secretion in the lung alveolar fluid were significantly elevated in mice vaccinated with LAIV. Moreover, T-cell depletion of LAIV vaccinated mice compromised protection, indicating that T-cell-mediated immunity is required. In contrast, passive transfer of sera from mice vaccinated with LAIV into naïve mice failed to protect against PR8 challenge. Neutralization assays in vitro confirmed that LAIV did not induce cross-strain neutralizing antibodies against PR8 virus. Finally, we showed that three doses of LAIV also provided protection against challenge with two additional heterologous viruses, FM/47 and HK/68. These results support the potential use of the LAIV as a universal influenza vaccine under a prime-boost vaccination regimen. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Influenza Vaccination in Young Children Reduces Influenza-Associated Hospitalizations in Older Adults, 2002–2006

PubMed Central

Cohen, Steven A.; Chui, Kenneth K.H.; Naumova, Elena N.

2011-01-01

OBJECTIVES To assess how influenza vaccination coverage in children is related to pneumonia and influenza (P&I) in US seniors and if these associations are modified by sociodemographic factors. DESIGN We abstracted approximately 5 million hospitalization records from the Centers for Medicare and Medicaid Services for four influenza years, 2002–2006. We estimated a single year age distribution of rates of P&I hospitalization by state for each influenza season and observed an exponential acceleration in the P&I rates with age for each influenza season. State-and season-specific P&I rate accelerations were regressed against the percentage of vaccinated children, seniors, or both using mixed effects models. SETTING United States population, 2002–2006 PARTICIPANTS US population aged 65 and above MEASUREMENTS State-level influenza annual vaccination coverage data in children and seniors were obtained from the National Immunization Survey and the Behavioral Risk Factor Surveillance System, respectively. RESULTS Child influenza vaccination coverage was negatively associated with age acceleration in P&I, whereas influenza vaccination in the seniors themselves was not significantly associated with P&I in seniors. CONCLUSION Vaccination of children against influenza may induce herd immunity against influenza for seniors and has the potential to be more beneficial to seniors than the existing policy to prevent influenza by vaccinating seniors themselves. PMID:21275932

Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus

PubMed Central

Melo, Rossana C. N.; Duan, Susu; LeMessurier, Kim S.; Liedmann, Swantje; Surman, Sherri L.; Lee, James J.; Hurwitz, Julia L.; Thomas, Paul G.; McCullers, Jonathan A.

2017-01-01

Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus–infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8+ T cell numbers in the airways. In vitro assays with primary or bone marrow–derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide–exposed eosinophils induced CD8+ T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity. PMID:28283567

The emerging Haemophilus influenzae serotype a infection and a potential vaccine: Implementation science in action

PubMed Central

Barreto, L; Cox, AD; Ulanova, M; Bruce, MG; Tsang, RSW

2017-01-01

Haemophilus influenzae serotype b (Hib) was a major cause of meningitis in children until Hib conjugate vaccine was introduced into the routine infant immunization program and Hib disease in children was almost eliminated. In Alaska, northern Canada and other countries with Indigenous peoples, H. influenzae serotype a (Hia) has emerged as a significant cause of pneumonia, meningitis and septic arthritis especially in children under 24 months of age. A joint government initiative between the Public Health Agency of Canada (PHAC) and the National Research Council of Canada (NRC) was carried out to assess whether an Hia vaccine could be developed for the common good. The initiative included strategic partnerships with clinician researchers in Thunder Bay, Ontario who provide health services to Indigenous people and the Artic Investigations Program (AIP) of the United States Centers for Disease Control and Prevention (CDC) in Alaska. This government initiated and funded research identified that the development of an Hia vaccine is possible and ongoing surveillance that includes strain characterization is essential to understand the potential spread of Hia in North America and around the world. PMID:29770070

The emerging Haemophilus influenzae serotype a infection and a potential vaccine: Implementation science in action.

PubMed

Barreto, L; Cox, A D; Ulanova, M; Bruce, M G; Tsang, Rsw

2017-05-04

Haemophilus influenzae serotype b (Hib) was a major cause of meningitis in children until Hib conjugate vaccine was introduced into the routine infant immunization program and Hib disease in children was almost eliminated. In Alaska, northern Canada and other countries with Indigenous peoples, H. influenzae serotype a (Hia) has emerged as a significant cause of pneumonia, meningitis and septic arthritis especially in children under 24 months of age. A joint government initiative between the Public Health Agency of Canada (PHAC) and the National Research Council of Canada (NRC) was carried out to assess whether an Hia vaccine could be developed for the common good. The initiative included strategic partnerships with clinician researchers in Thunder Bay, Ontario who provide health services to Indigenous people and the Artic Investigations Program (AIP) of the United States Centers for Disease Control and Prevention (CDC) in Alaska. This government initiated and funded research identified that the development of an Hia vaccine is possible and ongoing surveillance that includes strain characterization is essential to understand the potential spread of Hia in North America and around the world.

Bringing influenza vaccines into the 21st century

PubMed Central

Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino

2014-01-01

The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and ‘universal’ flu vaccines, offer a promise of a dramatically improved influenza vaccine system. PMID:24378716

Bringing influenza vaccines into the 21st century.

PubMed

Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino

2014-01-01

The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and 'universal' flu vaccines, offer a promise of a dramatically improved influenza vaccine system.

Immunizations and Developmental Milestones for Your Child from Birth Through 6 Years Old

MedlinePlus

... type b n Hib Pneumococcal n PCV Inactivated Poliovirus n IPV Influenza (Flu) Milestones should be achieved ... type b n Hib Pneumococcal n PCV Inactivated Poliovirus n IPV Influenza (Flu) n Influenza, first dose ...

Integration of Immune Cell Populations, mRNA-Seq, and CpG Methylation to Better Predict Humoral Immunity to Influenza Vaccination: Dependence of mRNA-Seq/CpG Methylation on Immune Cell Populations

PubMed Central

Zimmermann, Michael T.; Kennedy, Richard B.; Grill, Diane E.; Oberg, Ann L.; Goergen, Krista M.; Ovsyannikova, Inna G.; Haralambieva, Iana H.; Poland, Gregory A.

2017-01-01

The development of a humoral immune response to influenza vaccines occurs on a multisystems level. Due to the orchestration required for robust immune responses when multiple genes and their regulatory components across multiple cell types are involved, we examined an influenza vaccination cohort using multiple high-throughput technologies. In this study, we sought a more thorough understanding of how immune cell composition and gene expression relate to each other and contribute to interindividual variation in response to influenza vaccination. We first hypothesized that many of the differentially expressed (DE) genes observed after influenza vaccination result from changes in the composition of participants’ peripheral blood mononuclear cells (PBMCs), which were assessed using flow cytometry. We demonstrated that DE genes in our study are correlated with changes in PBMC composition. We gathered DE genes from 128 other publically available PBMC-based vaccine studies and identified that an average of 57% correlated with specific cell subset levels in our study (permutation used to control false discovery), suggesting that the associations we have identified are likely general features of PBMC-based transcriptomics. Second, we hypothesized that more robust models of vaccine response could be generated by accounting for the interplay between PBMC composition, gene expression, and gene regulation. We employed machine learning to generate predictive models of B-cell ELISPOT response outcomes and hemagglutination inhibition (HAI) antibody titers. The top HAI and B-cell ELISPOT model achieved an area under the receiver operating curve (AUC) of 0.64 and 0.79, respectively, with linear model coefficients of determination of 0.08 and 0.28. For the B-cell ELISPOT outcomes, CpG methylation had the greatest predictive ability, highlighting potentially novel regulatory features important for immune response. B-cell ELISOT models using only PBMC composition had lower performance (AUC = 0.67), but highlighted well-known mechanisms. Our analysis demonstrated that each of the three data sets (cell composition, mRNA-Seq, and DNA methylation) may provide distinct information for the prediction of humoral immune response outcomes. We believe that these findings are important for the interpretation of current omics-based studies and set the stage for a more thorough understanding of interindividual immune responses to influenza vaccination. PMID:28484452

Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells.

PubMed

Hussain, Althaf I; Cordeiro, Melissa; Sevilla, Elizabeth; Liu, Jonathan

2010-05-14

Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced influenza viruses. Based on these study results we conclude that the MDCK cell produced and egg produced vaccine strains are highly comparable. Copyright 2010 Elsevier Ltd. All rights reserved.

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection.

PubMed

Merani, Shahzma; Pawelec, Graham; Kuchel, George A; McElhaney, Janet E

2017-01-01

The number of people over the age of 60 is expected to double by 2050 according to the WHO. This emphasizes the need to ensure optimized resilience to health stressors in late life. In older adults, influenza is one of the leading causes of catastrophic disability (defined as the loss of independence in daily living and self-care activities). Influenza vaccination is generally perceived to be less protective in older adults, with some studies suggesting that the humoral immune response to the vaccine is further impaired in cytomegalovirus (CMV)-seropositive older people. CMV is a β-herpes virus infection that is generally asymptomatic in healthy individuals. The majority of older adults possess serum antibodies against the virus indicating latent infection. Age-related changes in T-cell-mediated immunity are augmented by CMV infection and may be associated with more serious complications of influenza infection. This review focuses on the impact of aging and CMV on immune cell function, the response to influenza infection and vaccination, and how the current understanding of aging and CMV can be used to design a more effective influenza vaccine for older adults. It is anticipated that efforts in this field will address the public health need for improved protection against influenza in older adults, particularly with regard to the serious complications leading to loss of independence.

Complete Protection against Influenza Virus H1N1 Strain A/PR/8/34 Challenge in Mice Immunized with Non-Adjuvanted Novirhabdovirus Vaccines

PubMed Central

Rouxel, Ronan N.; Mérour, Emilie; Biacchesi, Stéphane; Brémont, Michel

2016-01-01

Novirhabdoviruses like Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious Hematopoietic Necrosis Virus (IHNV) are fish-infecting Rhabdoviruses belonging to the Mononegavirales order. By reverse genetics, we previously showed that a recombinant VHSV expressing the West Nile Virus (WNV) E glycoprotein could serve as a vaccine platform against WNV. In the current study, we aimed to evaluate the potential of the Novirhabdovirus platform as a vaccine against influenza virus. Recombinant Novirhabdoviruses, rVHSV-HA and rIHNV-HA, expressing at the viral surface the hemagglutinin HA ectodomain were generated and used to immunized mice. We showed that mice immunized with either, rVHSV-HA or rIHNV-HA, elicited a strong neutralizing antibody response against influenza virus. A complete protection was conferred to the immunized mice when challenged with a lethal dose of influenza H1N1 A/PR/8/34 virus. Furthermore we showed that although acting as inert antigen in mice, since naturally inactivated over 20°C, mice immunized with rVHSV-HA or rIHNV-HA in the absence of adjuvant were also completely protected from a lethal challenge. Novirhabdoviruses platform are of particular interest as vaccines for mammals since they are cost effective to produce, relatively easy to generate and very effective to protect immunized animals. PMID:27711176

Mass Commuting and Influenza Vaccination Prevalence in New York City: Protection in a Mixing Environment

PubMed Central

Levine, Burton; Wilcosky, Tim; Wagener, Diane; Cooley, Phillip

2010-01-01

Objective Assess influenza vaccination among commuters using mass transit in New York City (NYC). Methods We used the 2006 NYC Community Health Survey (CHS) to analyze the prevalence of influenza immunization by commuting behaviors and to understand what socioeconomic and geographic factors may explain any differences found. Results Vaccination prevalence is significantly lower for New Yorkers who commute on public transportation compared to other New Yorkers. This difference is largely attenuated after adjusting for socio-demographic characteristics and neighborhood of residence. Conclusions The analysis identified a low prevalence of immunization among commuters, and given the transmissibility in that setting, targeting commuters for vaccination campaigns may impede influenza spread. PMID:21218159

Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays.

PubMed

Cwach, Kevin T; Sandbulte, Heather R; Klonoski, Joshua M; Huber, Victor C

2012-03-01

Prior to detection of an antibody response toward influenza viruses using the hemagglutination inhibition assay (HAI), sera are routinely treated to inactivate innate inhibitors using both heat inactivation (56°C) and recombinant neuraminidase [receptor-destroying enzyme (RDE)]. We revisited the contributions of innate serum inhibitors toward interference with influenza viruses in immune assays, using murine sera, with emphasis on the interactions with influenza A viruses of the H3N2 subtype. We used individual serum treatments: 56°C alone, RDE alone, or RDE + 56°C, to treat sera prior to evaluation within HAI, microneutralization, and macrophage uptake assays. Our data demonstrate that inhibitors present within untreated murine sera interfere with the HAI assay in a manner that is different from that seen for the microneutralization assay. Specifically, the γ class inhibitor α(2) -Macroglobulin (A2-M) can inhibit H3N2 viruses within the HAI assay, but not in the microneutralization assay. Based on these findings, we used a macrophage uptake assay to demonstrate that these inhibitors can increase uptake by macrophages when the influenza viruses express an HA from a 1968 H3N2 virus isolate, but not a 1997 H3N2 isolate. The practice of treating sera to inactivate innate inhibitors of influenza viruses prior to evaluation within immune assays has allowed us to effectively detect influenza virus-specific antibodies for decades. However, this practice has yielded an under-appreciation for the contribution of innate serum inhibitors toward host immune responses against these viruses, including contributions toward neutralization and macrophage uptake. © 2011 Blackwell Publishing Ltd.

Prediction of common epitopes on hemagglutinin of the influenza A virus (H1 subtype).

PubMed

Guo, Chunyan; Xie, Xin; Li, Huijin; Zhao, Penghua; Zhao, Xiangrong; Sun, Jingying; Wang, Haifang; Liu, Yang; Li, Yan; Hu, Qiaoxia; Hu, Jun; Li, Yuan

2015-02-01

Influenza A virus infection is a persistent threat to public health worldwide due to hemagglutinin (HA) variation. Current vaccines against influenza A virus provide immunity to viral isolates similar to vaccine strains. Antibodies against common epitopes provide immunity to diverse influenza virus strains and protect against future pandemic influenza. Therefore, it is vital to analyze common HA antigenic epitopes of influenza virus. In this study, 14 strains of monoclonal antibodies with high sensitivity to common epitopes of influenza virus antigens identified in our previous study were selected as the tool to predict common HA epitopes. The common HA antigenic epitopes were divided into four categories by ELISA blocking experiments, and separately, into three categories according to the preliminary results of computer simulation. Comparison between the results of computer simulations and ELISA blocking experiments indicated that at least two classes of common epitopes are present in influenza virus HA. This study provides experimental data for improving the prediction of HA epitopes of influenza virus (H1 subtype) and the development of a potential universal vaccine as well as a novel approach for the prediction of epitopes on other pathogenic microorganisms. Copyright © 2014 Elsevier Inc. All rights reserved.

Swine influenza and vaccines: an alternative approach for decision making about pandemic prevention.

PubMed

Basili, Marcello; Ferrini, Silvia; Montomoli, Emanuele

2013-08-01

During the global pandemic of A/H1N1/California/07/2009 (A/H1N1/Cal) influenza, many governments signed contracts with vaccine producers for a universal influenza immunization program and bought hundreds of millions of vaccines doses. We argue that, as Health Ministers assumed the occurrence of the worst possible scenario (generalized pandemic influenza) and followed the strong version of the Precautionary Principle, they undervalued the possibility of mild or weak pandemic wave. An alternative decision rule, based on the non-extensive entropy principle, is introduced, and a different Precautionary Principle characterization is applied. This approach values extreme negative results (catastrophic events) in a different way and predicts more plausible and mild events. It introduces less pessimistic forecasts in the case of uncertain influenza pandemic outbreaks. A simplified application is presented using seasonal data of morbidity and severity among Italian children influenza-like illness for the period 2003-10. Established literature results predict an average attack rate of not less than 15% for the next pandemic influenza [Meltzer M, Cox N, Fukuda K. The economic impact of pandemic influenza in the United States: implications for setting priorities for interventions. Emerg Infect Dis 1999;5:659-71; Meltzer M, Cox N, Fukuda K. Modeling the Economic Impact of Pandemic Influenza in the United States: Implications for Setting Priorities for Intervention. Background paper. Atlanta, GA: CDC, 1999. Available at: http://www.cdc.gov/ncidod/eid/vol5no5/melt_back.htm (7 January 2011, date last accessed))]. The strong version of the Precautionary Principle would suggest using this prediction for vaccination campaigns. On the contrary, the non-extensive maximum entropy principle predicts a lower attack rate, which induces a 20% saving in public funding for vaccines doses. The need for an effective influenza pandemic prevention program, coupled with an efficient use of public funding, calls for a rethinking of the Precautionary Principle. The non-extensive maximum entropy principle, which incorporates vague and incomplete information available to decision makers, produces a more coherent forecast of possible influenza pandemic and a conservative spending in public funding.

Intranasal vaccination with replication defective adenovirus-5 encoding influenza hemagglutinin elicits protective immunity to homologous challenge and partial protection to heterologous challenge in pigs

USDA-ARS?s Scientific Manuscript database

Influenza A virus (IAV) is widely circulating in the swine population and causes significant economic loss. To combat IAV infection the swine industry utilizes adjuvanted whole inactivated virus (WIV) vaccines. These vaccines can provide sterilizing immunity towards homologous virus but often have l...

Comparison of Humoral and Cellular Immune Responses to Inactivated Swine Influenza Virus Vaccine in Weaned Pigs

USDA-ARS?s Scientific Manuscript database

Purpose: To evaluate and compare humoral and cellular immune responses to inactivated swine influenza virus (SIV) vaccine. Methods: Fifty 3-week-old weaned pigs from a herd free of SIV and PRRSV were randomly divided into the non-vaccinated control group and vaccinated group containing 25 pigs each....

Comparison of Humoral and Cellular Immune Responses to Inactivated Swine Influenza Virus Vaccine in Weaned Pigs

USDA-ARS?s Scientific Manuscript database

Humoral and cellular immune responses to inactivated swine influenza virus (SIV) vaccine were evaluated and compared. Fifty 3-week-old weaned pigs from a herd free of SIV and PRRSV were randomly divided into the non-vaccinated control group and vaccinated group containing 25 pigs each. Pigs were va...

Influence of maternal immunity on vaccine efficacy and susceptibility of commercial broilers against highly pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

Maternal antibodies provide early protection from disease, but may interfere with the vaccination efficacy in short-lived broilers. This study seeks to assess how maternal immunity can interfere with vaccine efficacy against clade 2.3.4.4 H5N2 highly pathogenic avian influenza virus (HPAIV) and how ...

Effects of pre-existing orthopoxvirus-specific immunity on the performance of Modified Vaccinia virus Ankara-based influenza vaccines.

PubMed

Altenburg, Arwen F; van Trierum, Stella E; de Bruin, Erwin; de Meulder, Dennis; van de Sandt, Carolien E; van der Klis, Fiona R M; Fouchier, Ron A M; Koopmans, Marion P G; Rimmelzwaan, Guus F; de Vries, Rory D

2018-04-24

The replication-deficient orthopoxvirus modified vaccinia virus Ankara (MVA) is a promising vaccine vector against various pathogens and has an excellent safety record. However, pre-existing vector-specific immunity is frequently suggested to be a drawback of MVA-based vaccines. To address this issue, mice were vaccinated with MVA-based influenza vaccines in the presence or absence of orthopoxvirus-specific immunity. Importantly, protective efficacy of an MVA-based influenza vaccine against a homologous challenge was not impaired in the presence of orthopoxvirus-specific pre-existing immunity. Nonetheless, orthopoxvirus-specific pre-existing immunity reduced the induction of antigen-specific antibodies under specific conditions and completely prevented induction of antigen-specific T cell responses by rMVA-based vaccination. Notably, antibodies induced by vaccinia virus vaccination, both in mice and humans, were not capable of neutralizing MVA. Thus, when using rMVA-based vaccines it is important to consider the main correlate of protection induced by the vaccine, the vaccine dose and the orthopoxvirus immune status of vaccine recipients.

Cytomegalovirus infection enhances the immune response to influenza.

PubMed

Furman, David; Jojic, Vladimir; Sharma, Shalini; Shen-Orr, Shai S; Angel, Cesar J L; Onengut-Gumuscu, Suna; Kidd, Brian A; Maecker, Holden T; Concannon, Patrick; Dekker, Cornelia L; Thomas, Paul G; Davis, Mark M

2015-04-01

Cytomegalovirus (CMV) is a β-herpesvirus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli, and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV status. In contrast, CMV-seropositive young adults exhibited enhanced antibody responses to influenza vaccination, increased CD8(+) T cell sensitivity, and elevated levels of circulating interferon-γ compared to seronegative individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the ubiquity of CMV infection in humans and many other species. Copyright © 2015, American Association for the Advancement of Science.

Invasive bacterial diseases: national surveillance in Italy and vaccination coverage in the Local Health Agency 4 "Chiavarese", Liguria region (Italy).

PubMed

Trucchi, C; Zoppi, G

2012-06-01

In 2007 in Italy, the National Institute of Health published a new protocol for the National Surveillance of Invasive Bacterial Diseases, in order to enhance the notification system of these diseases and to improve immunization strategies. Available vaccines to prevent these diseases were introduced for the first time into the 1999-2000 National Immunization Plan (NIP) (vaccination against Haemophilus influenzae type b) and the 2005-2007 NIP (vaccination against Streptococcus pneumoniae and Neisseria meningitidis serogroup C). We evaluated the frequency of invasive diseases, on the basis of the number of notifications, the different immunization strategies in the Italian Regions and the vaccination coverage in Local Health Agency 4 "Chiavarese" (LHA) in the Liguria Region (Italy). We evaluated the number of notifications of invasive diseases collected by the national databank coordinated by the ISS (Informative System of Infectious Diseases, SIMI) from 1994 to 2011. We also examined regional regulations concerning immunization policies. Immunization coverage was calculated by means of the "OASIS" software (version 9.0.0) used in our LHA. Available data indicate that the large-scale vaccination policy begun in 1999 in Italy has led to a great reduction in Haemophilus influenzae-related diseases in the pediatric age. Meningococcal diseases have declined to a lesser degree; this is due to the more recent introduction of vaccination against serogroup C (in 2005), the variability of the immunization strategies adopted in the different Italian Regions and the availability of the vaccination against serogroup C only in the pediatric age. The diseases caused by Streptococcus pneumoniae seem to have increased since 2007 because of the implementation of the Surveillance of Invasive Diseases Program and the subsequent notification of all invasive diseases (not only meningitis). Furthermore, the various Italian Regions have adopted different immunization strategies against this disease, too. We evaluated vaccination coverage in LHA 4 from 2003 to 2008. VC levels against Haemophilus influenzae are excellent; the objective indicated in the 2005-2007 NIP (> or = 95%) has therefore been reached. Vaccination coverage levels against Streptococcus pneumoniae and Neisseria meningitidis serogroup C at the 24th month of age are also good. However, we need to implement specific immunization strategies for adolescents, since the vaccination coverage levels are not completely satisfactory. The improvement of the national invasive disease surveillance system has provided better knowledge of the size of the problem and the impact of immunization strategies on the incidence of invasive bacterial diseases. Furthermore, immunization policies in Italy display territorial heterogeneity. Vaccination coverage levels against Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis at the 24th month in LHA 4 are very high. In adolescents (15 year-olds) the immunization coverage are good but needs to be improved through specific strategies, such as raising the awareness of healthcare workers, involving general practitioners and educating the target population.

Influenza A (H1N1) 2009 monovalent and seasonal influenza vaccination among adults 25 to 64 years of age with high-risk conditions—United States, 2010

PubMed Central

Lu, Peng-jun; Gonzalez-Feliciano, Amparo; Ding, Helen; Bryan, Leah N.; Yankey, David; Monsell, Elizabeth A.; Greby, Stacie M.; Euler, Gary L.

2018-01-01

Background Seasonal influenza vaccination has been routinely recommended for adults with high-risk conditions. The Advisory Committee on Immunization Practices recommended that persons 25 to 64 years of age with high-risk conditions be one of the initial target groups to receive H1N1 vaccination during the 2009-2010 season. Methods We used data from the 2009-2010 Behavioral Risk Factor Surveillance System survey. Vaccination levels of H1N1 and seasonal influenza vaccination among respondents 25 to 64 years with high-risk conditions were assessed. Multivariable logistic regression models were performed to identify factors independently associated with vaccination. Results Overall, 24.8% of adults 25 to 64 years of age were identified to have high-risk conditions. Among adults 25 to 64 years of age with high-risk conditions, H1N1 and seasonal vaccination coverage were 26.3% and 47.6%, respectively. Characteristics independently associated with an increased likelihood of H1N1 vaccination were as follows: higher age; Hispanic race/ethnicity; medical insurance; ability to see a doctor if needed; having a primary doctor; a routine checkup in the previous year; not being a current smoker; and having high-risk conditions other than asthma, diabetes, and heart disease. Characteristics independently associated with seasonal influenza vaccination were similar compared with factors associated with H1N1 vaccination. Conclusion Immunization programs should work with provider organizations to review efforts made to reach adults with high-risk conditions during the recent pandemic and assess how and where they can increase vaccination coverage during future pandemics. PMID:23419613

ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways

PubMed Central

Kuriakose, Teneema; Man, Si Ming; Malireddi, R.K. Subbarao; Karki, Rajendra; Kesavardhana, Sannula; Place, David E.; Neale, Geoffrey; Vogel, Peter; Kanneganti, Thirumala-Devi

2016-01-01

The interferon-inducible protein Z-DNA binding protein 1 (ZBP1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1) was identified as a dsDNA sensor, which instigates innate immune responses. However, this classification has been disputed and whether ZBP1 functions as a pathogen sensor during an infection has remained unknown. Herein, we demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the RIPK1–RIPK3–Caspase-8 axis. ZBP1 regulates NLRP3 inflammasome activation as well as induction of apoptosis, necroptosis and pyroptosis in IAV-infected cells. Importantly, ZBP1 deficiency protected mice from mortality during IAV infection owing to reduced inflammatory responses and epithelial damage. Overall, these findings indicate that ZBP1 is an innate immune sensor of IAV and highlight its importance in the pathogenesis of IAV infection. PMID:27917412

Vaccination and auto-immune rheumatic diseases: lessons learnt from the 2009 H1N1 influenza virus vaccination campaign.

PubMed

Touma, Zahi; Gladman, Dafna D; Urowitz, Murray B

2013-03-01

To determine the safety and efficacy of adjuvant and nonadjuvant influenza A/H1NI vaccination in patients with rheumatic diseases. Due to immune abnormalities and the use of steroids and immunosuppressant treatment, patients with rheumatic diseases are susceptible to infections including influenza. Infections continue to be one of the leading causes of morbidity and mortality in rheumatic diseases, partly due to the disease processes and partly due to medications. Viral infections are particularly an issue, so vaccinations would be advisable. However, because of the abnormalities in immune mechanisms in many rheumatic diseases, it is not clear whether vaccinations are well tolerated and effective. A number of studies confirmed the efficacy and safety of adjuvant and nonadjuvant influenza A/H1NI vaccination in patients with rheumatic diseases. The potential side effects associated with H1N1 vaccines were not different from those observed with seasonal influenza vaccine. The use of steroids and immunosuppressant therapies may alter the efficacy of the vaccines. Adjuvant and nonadjuvant influenza A/H1NI vaccinations have no clinically important effect on production or levels of autoantibodies in patients with rheumatic diseases. H1N1 vaccination should be given to patients with rheumatic diseases.

Options and obstacles for designing a universal influenza vaccine.

PubMed

Jang, Yo Han; Seong, Baik Lin

2014-08-18

Since the discovery of antibodies specific to a highly conserved stalk region of the influenza virus hemagglutinin (HA), eliciting such antibodies has been considered the key to developing a universal influenza vaccine that confers broad-spectrum protection against various influenza subtypes. To achieve this goal, a prime/boost immunization strategy has been heralded to redirect host immune responses from the variable globular head domain to the conserved stalk domain of HA. While this approach has been successful in eliciting cross-reactive antibodies against the HA stalk domain, protective efficacy remains relatively poor due to the low immunogenicity of the domain, and the cross-reactivity was only within the same group, rather than among different groups. Additionally, concerns are raised on the possibility of vaccine-associated enhancement of viral infection and whether multiple boost immunization protocols would be considered practical from a clinical standpoint. Live attenuated vaccine hitherto remains unexplored, but is expected to serve as an alternative approach, considering its superior cross-reactivity. This review summarizes recent advancements in the HA stalk-based universal influenza vaccines, discusses the pros and cons of these approaches with respect to the potentially beneficial and harmful effects of neutralizing and non-neutralizing antibodies, and suggests future guidelines towards the design of a truly protective universal influenza vaccine.

Options and Obstacles for Designing a Universal Influenza Vaccine

PubMed Central

Jang, Yo Han; Seong, Baik Lin

2014-01-01

Since the discovery of antibodies specific to a highly conserved stalk region of the influenza virus hemagglutinin (HA), eliciting such antibodies has been considered the key to developing a universal influenza vaccine that confers broad-spectrum protection against various influenza subtypes. To achieve this goal, a prime/boost immunization strategy has been heralded to redirect host immune responses from the variable globular head domain to the conserved stalk domain of HA. While this approach has been successful in eliciting cross-reactive antibodies against the HA stalk domain, protective efficacy remains relatively poor due to the low immunogenicity of the domain, and the cross-reactivity was only within the same group, rather than among different groups. Additionally, concerns are raised on the possibility of vaccine-associated enhancement of viral infection and whether multiple boost immunization protocols would be considered practical from a clinical standpoint. Live attenuated vaccine hitherto remains unexplored, but is expected to serve as an alternative approach, considering its superior cross-reactivity. This review summarizes recent advancements in the HA stalk-based universal influenza vaccines, discusses the pros and cons of these approaches with respect to the potentially beneficial and harmful effects of neutralizing and non-neutralizing antibodies, and suggests future guidelines towards the design of a truly protective universal influenza vaccine. PMID:25196381

Prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (ACIP).

PubMed

Briere, Elizabeth C; Rubin, Lorry; Moro, Pedro L; Cohn, Amanda; Clark, Thomas; Messonnier, Nancy

2014-02-28

This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of Haemophilus influenzae type b (Hib) disease in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians, public health officials, vaccination providers, and immunization program personnel as a resource. ACIP recommends routine vaccination with a licensed conjugate Hib vaccine for infants aged 2 through 6 months (2 or 3 doses, depending on vaccine product) with a booster dose at age 12 through 15 months. ACIP also recommends vaccination for certain persons at increased risk for Hib disease (i.e., persons who have early component complement deficiencies, immunoglobulin deficiency, anatomic or functional asplenia, or HIV infection; recipients of hematopoietic stem cell transplant; and recipients of chemotherapy or radiation therapy for malignant neoplasms). This report summarizes current information on Hib epidemiology in the United States and describes Hib vaccines licensed for use in the United States. Guidelines for antimicrobial chemoprophylaxis of contacts of persons with Hib disease also are provided.

Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry

DTIC Science & Technology

2007-05-30

Intercontinental circulation of human influenza A( H1N2 ) reassortant viruses during the 2001–2002 influenza season. J Infect Dis 186: 1490–1493. 6. Taubenberger...Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry Rangarajan Sampath1*, Kevin L. Russell2, Christian Massire1, Mark W...Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, United States of America Background. Effective influenza surveillance requires

Using the Ferret as an Animal Model for Investigating Influenza Antiviral Effectiveness

PubMed Central

Oh, Ding Y.; Hurt, Aeron C.

2016-01-01

The concern of the emergence of a pandemic influenza virus has sparked an increased effort toward the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titer of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness. PMID:26870031

Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: A pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS Network).

PubMed

Nichols, Michaela K; Andrew, Melissa K; Hatchette, Todd F; Ambrose, Ardith; Boivin, Guy; Bowie, William; Chit, Ayman; Dos Santos, Gael; ElSherif, May; Green, Karen; Haguinet, Francois; Halperin, Scott A; Ibarguchi, Barbara; Johnstone, Jennie; Katz, Kevin; Lagacé-Wiens, Phillipe; Langley, Joanne M; LeBlanc, Jason; Loeb, Mark; MacKinnon-Cameron, Donna; McCarthy, Anne; McElhaney, Janet E; McGeer, Allison; Poirier, Andre; Powis, Jeff; Richardson, David; Schuind, Anne; Semret, Makeda; Shinde, Vivek; Smith, Stephanie; Smyth, Daniel; Stiver, Grant; Taylor, Geoffrey; Trottier, Sylvie; Valiquette, Louis; Webster, Duncan; Ye, Lingyun; McNeil, Shelly A

2018-04-12

Ongoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons. The Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death. Overall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4-48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4-47.8%) and 48.0% (95% CI: 37.5-56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8-65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0-88.4%). While effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability. ClinicalTrials.gov Identifier: NCT01517191. Copyright © 2018 Elsevier Ltd. All rights reserved.

H1N1 antibody persistence 1 year after immunization with an adjuvanted or whole-virion pandemic vaccine and immunogenicity and reactogenicity of subsequent seasonal influenza vaccine: a multicenter follow-on study.

PubMed

Walker, Woolf T; de Whalley, Philip; Andrews, Nick; Oeser, Clarissa; Casey, Michelle; Michaelis, Louise; Hoschler, Katja; Harrill, Caroline; Moulsdale, Phoebe; Thompson, Ben; Jones, Claire; Chalk, Jem; Kerridge, Simon; John, Tessa M; Okike, Ifeanyichukwu; Ladhani, Shamez; Tomlinson, Richard; Heath, Paul T; Miller, Elizabeth; Faust, Saul N; Snape, Matthew D; Finn, Adam; Pollard, Andrew J

2012-03-01

We investigated antibody persistence in children 1 year after 2 doses of either an AS03(B)-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03(B)-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%-100%) vs 32.4% (95% CI, 21.5%-44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%-99.4%) vs 65.9% (95% CI, 55.3%-75.5%) in those 3-12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03(B)-adjuvanted vaccine. This study provides serological evidence that 2 doses of AS03(B)-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

PubMed Central

Walker, Woolf T.; de Whalley, Philip; Andrews, Nick; Oeser, Clarissa; Casey, Michelle; Michaelis, Louise; Hoschler, Katja; Harrill, Caroline; Moulsdale, Phoebe; Thompson, Ben; Jones, Claire; Chalk, Jem; Kerridge, Simon; John, Tessa M.; Okike, Ifeanyichukwu; Ladhani, Shamez; Tomlinson, Richard; Heath, Paul T.; Miller, Elizabeth; Snape, Matthew D.; Finn, Adam; Pollard, Andrew J.

2012-01-01

Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain. PMID:22267719

Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study.

PubMed

Hayward, Andrew C; Wang, Lili; Goonetilleke, Nilu; Fragaszy, Ellen B; Bermingham, Alison; Copas, Andrew; Dukes, Oliver; Millett, Elizabeth R C; Nazareth, Irwin; Nguyen-Van-Tam, Jonathan S; Watson, John M; Zambon, Maria; Johnson, Anne M; McMichael, Andrew J

2015-06-15

A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. We quantified influenza A(H3N2) virus-specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.

Natural T Cell–mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study

PubMed Central

Wang, Lili; Goonetilleke, Nilu; Fragaszy, Ellen B.; Bermingham, Alison; Copas, Andrew; Dukes, Oliver; Millett, Elizabeth R. C.; Nazareth, Irwin; Nguyen-Van-Tam, Jonathan S.; Watson, John M.; Zambon, Maria; Johnson, Anne M.; McMichael, Andrew J.

2015-01-01

Rationale: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. Objectives: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. Methods: We quantified influenza A(H3N2) virus–specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. Measurements and Main Results: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11–0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. Conclusions: Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity. PMID:25844934

Mucosal Immunization with a Candidate Universal Influenza Vaccine Reduces Virus Transmission in a Mouse Model

PubMed Central

Lo, Chia-Yun; Misplon, Julia A.; Epstein, Suzanne L.

2014-01-01

ABSTRACT Pandemic influenza is a major public health concern, but conventional strain-matched vaccines are unavailable early in a pandemic. Candidate “universal” vaccines targeting the viral antigens nucleoprotein (NP) and matrix 2 (M2), which are conserved among all influenza A virus strains and subtypes, could be manufactured in advance for use at the onset of a pandemic. These vaccines do not prevent infection but can reduce disease severity, deaths, and virus titers in the respiratory tract. We hypothesized that such immunization may reduce virus transmission from vaccinated, infected animals. To investigate this hypothesis, we studied mouse models for direct-contact and airborne transmission of H1N1 and H3N2 influenza viruses. We established conditions under which virus transmission occurs and showed that transmission efficiency is determined in part at the level of host susceptibility to infection. Our findings indicate that virus transmission between mice has both airborne and direct-contact components. Finally, we demonstrated that immunization with recombinant adenovirus vectors expressing NP and M2 significantly reduced the transmission of virus to cohoused, unimmunized mice in comparison to controls. These findings have broad implications for the impact of conserved-antigen vaccines, not only in protecting the vaccinated individual but also in protecting others by limiting influenza virus transmission and potentially reducing the size of epidemics. IMPORTANCE Using a mouse model of influenza A virus transmission, we demonstrate that a candidate “universal” influenza vaccine both protects vaccinated animals from lethal infection and reduces the transmission of virus from vaccinated to nonvaccinated mice. This vaccine induces immunity against proteins conserved among all known influenza A virus strains and subtypes, so it could be used early in a pandemic before conventional strain-matched vaccines are available and could potentially reduce the spread of infection in the community. PMID:24623430

Differential Immune Profiles in Two Pandemic Influenza A(H1N1)pdm09 Virus Waves at Pandemic Epicenter.

PubMed

Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Rodríguez-Abrego, Gabriela; Mancilla-Herrera, Ismael; Domínguez-Cerezo, Esteban; Valero-Pacheco, Nuriban; Pérez-Toledo, Marisol; Lozano-Patiño, Fernando; Laredo-Sánchez, Fernando; Malagón-Rangel, José; Nellen-Hummel, Haiko; González-Bonilla, César; Arteaga-Troncoso, Gabriel; Cérbulo-Vázquez, Arturo; Pastelin-Palacios, Rodolfo; Klenerman, Paul; Isibasi, Armando; López-Macías, Constantino

2015-11-01

Severe influenza A(H1N1)pdm2009 virus infection cases are characterized by sustained immune activation during influenza pandemics. Seasonal flu data suggest that immune mediators could be modified by wave-related changes. Our aim was to determine the behavior of soluble and cell-related mediators in two waves at the epicenter of the 2009 influenza pandemic. Leukocyte surface activation markers were studied in serum from peripheral blood samples, collected from the 1(st) (April-May, 2009) and 2(nd) (October 2009-February 2010) pandemic waves. Patients with confirmed influenza A(H1N1)pdm2009 virus infection (H1N1), influenza-like illness (ILI) or healthy donors (H) were analyzed. Serum IL-6, IL-4 and IL-10 levels were elevated in H1N1 patients from the 2(nd) pandemic wave. Additionally, the frequency of helper and cytotoxic T cells was reduced during the 1(st) wave, whereas CD69 expression in helper T cells was increased in the 2(nd) wave for both H1N1 and ILI patients. In contrast, CD62L expression in granulocytes from the ILI group was increased in both waves but in monocytes only in the 2(nd) wave. Triggering Receptor Expressed on Myeloid cells (TREM)-1 expression was elevated only in H1N1 patients at the 1(st) wave. Our results show that during the 2009 influenza pandemic a T cell activation phenotype is observed in a wave-dependent fashion, with an expanded activation in the 2(nd) wave, compared to the 1(st) wave. Conversely, granulocyte and monocyte activation is infection-dependent. This evidence collected at the pandemic epicenter in 2009 could help us understand the differences in the underlying cellular mechanisms that drive the wave-related immune profile behaviors that occur against influenza viruses during pandemics. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

A cell culture-derived whole virus influenza A vaccine based on magnetic sulfated cellulose particles confers protection in mice against lethal influenza A virus infection.

PubMed

Pieler, Michael M; Frentzel, Sarah; Bruder, Dunja; Wolff, Michael W; Reichl, Udo

2016-12-07

Downstream processing and formulation of viral vaccines employs a large number of different unit operations to achieve the desired product qualities. The complexity of individual process steps involved, the need for time consuming studies towards the optimization of virus yields, and very high requirements regarding potency and safety of vaccines results typically in long lead times for the establishment of new processes. To overcome such obstacles, to enable fast screening of potential vaccine candidates, and to explore options for production of low cost veterinary vaccines a new platform for whole virus particle purification and formulation based on magnetic particles has been established. Proof of concept was carried out with influenza A virus particles produced in suspension Madin Darby canine kidney (MDCK) cells. The clarified, inactivated, concentrated, and diafiltered virus particles were bound to magnetic sulfated cellulose particles (MSCP), and directly injected into mice for immunization including positive and negative controls. We show here, that in contrast to the mock-immunized group, vaccination of mice with antigen-loaded MSCP (aMSCP) resulted in high anti-influenza A antibody responses and full protection against a lethal challenge with replication competent influenza A virus. Antiviral protection correlated with a 400-fold reduced number of influenza nucleoprotein gene copies in the lungs of aMSCP immunized mice compared to mock-treated animals, indicating the efficient induction of antiviral immunity by this novel approach. Thus, our data proved the use of MSCP for purification and formulation of the influenza vaccine to be fast and efficient, and to confer protection of mice against influenza A virus infection. Furthermore, the method proposed has the potential for fast purification of virus particles directly from bioreactor harvests with a minimum number of process steps towards formulation of low-cost veterinary vaccines, and for screening studies requiring fast purification protocols. Copyright © 2016 Elsevier Ltd. All rights reserved.

Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

PubMed Central

Machkovech, Heather M.; Bedford, Trevor; Suchard, Marc A.

2015-01-01

ABSTRACT Numerous experimental studies have demonstrated that CD8+ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8+ T cells. Here we use a novel computational approach to test for selection in CD8+ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8+ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8+ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8+ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. IMPORTANCE There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8+ T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal models and are associated with decreased symptoms in humans, no studies have proven with statistical significance that influenza virus evolves under positive selection to escape T cells. Here we use comparisons of human and swine influenza viruses to rigorously demonstrate that human influenza virus evolves under pressure to fix mutations in the nucleoprotein that promote escape from T cells. We further show that viruses with these mutations have a selective advantage since they are preferentially located on the “trunk” of the phylogenetic tree. Overall, our results show that CD8+ T cells targeting nucleoprotein play an important role in shaping influenza virus evolution. PMID:26311880

Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice.

PubMed

Kim, Eun Hye; Park, Hae-Jung; Han, Gye-Yeong; Song, Man-Ki; Pereboev, Alexander; Hong, Jeong S; Chang, Jun; Byun, Young-Ho; Seong, Baik Lin; Nguyen, Huan H

2014-09-01

Influenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. We report here that single intranasal immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA- and M2e-specific Ab responses, along with protection against heterosubtypic challenge in mice. The protection is superior compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus-neutralizing Abs, the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have an additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd-vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes. Current licensed influenza vaccines provide protection limited to the infection with same virus strains; therefore, the composition of influenza vaccines has to be revised every year. We have developed a new universal influenza vaccine that is highly efficient in induction of long-lasting cross-protection against different influenza virus strains. The cross-protection is associated with a high level of vaccine-induced antibodies against the conserved stalk domain of influenza virus hemagglutinin and the ectodomain of matrix protein. The vaccine could be used to stimulate cross-protective antibodies for the prevention and treatment of influenza with immediate effect for individuals who fail to respond to or receive the vaccine in due time. The vaccine offers a new tool to control influenza outbreaks, including pandemics. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines

PubMed Central

Gasper, David J.; Neldner, Brandon; Plisch, Erin H.; Rustom, Hani; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M.

2016-01-01

CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the respiratory tract. PMID:27997610

Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines.

PubMed

Gasper, David J; Neldner, Brandon; Plisch, Erin H; Rustom, Hani; Carrow, Emily; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M

2016-12-01

CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the respiratory tract.

Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 Virus.

PubMed

Klausberger, Miriam; Tscheliessnig, Rupert; Neff, Silke; Nachbagauer, Raffael; Wohlbold, Teddy John; Wilde, Monika; Palmberger, Dieter; Krammer, Florian; Jungbauer, Alois; Grabherr, Reingard

2016-01-01

Significant genetic variability in the head region of the influenza A hemagglutinin, the main target of current vaccines, makes it challenging to develop a long-lived seasonal influenza prophylaxis. Vaccines based on the conserved hemagglutinin stalk domain might provide broader cross-reactive immunity. However, this region of the hemagglutinin is immunosubdominant to the head region. Peptide-based vaccines have gained much interest as they allow the immune system to focus on relevant but less immunogenic epitopes. We developed a novel influenza A hemagglutinin-based display platform for H1 hemagglutinin stalk peptides that we identified in an epitope mapping assay using human immune sera and synthetic HA peptides. Flow cytometry and competition assays suggest that the identified stalk sequences do not recapitulate the epitopes of already described broadly neutralizing stalk antibodies. Vaccine constructs displaying 25-mer stalk sequences provided up to 75% protection from lethal heterologous virus challenge in BALB/c mice and induced antibody responses against the H1 hemagglutinin. The developed platform based on a vaccine antigen has the potential to be either used as stand-alone or as prime-vaccine in combination with conventional seasonal or pandemic vaccines for the amplification of stalk-based cross-reactive immunity in humans or as platform to evaluate the relevance of viral peptides/epitopes for protection against influenza virus infection.

Recombinant C-terminal 311 amino acids of HapS adhesin as a vaccine candidate for nontypeable Haemophilus influenzae: A study on immunoreactivity in Balb/C mouse.

PubMed

Tabatabaee Bafroee, Akram Sadat; Siadat, Seyed Davar; Mousavi, Seyed Fazlollah; Aghasadeghi, Mohammad Reza; Khorsand, Hashem; Nejati, Mehdi; Sadat, Seyed Mehdi; Mahdavi, Mehdi

2016-09-01

Hap, an auto-transporter protein, is an antigenically conserved adhesion protein which is present on both typeable and nontypeable Haemophilus influenzae. This protein has central role in bacterial attachment to respiratory tract epithelial cells. A 1000bp C-terminal fragment of Hap passenger domain (HapS) from nontypeable Haemophilus influenzae was cloned into a prokaryotic expression vector, pET-24a. BALB/c mice were immunized subcutaneously with purified rC-HapS. Serum IgG responses to purified rC-HapS, serum IgG subclasses were determined by ELISA and functional activity of antibodies was examined by Serum Bactericidal Assay. The output of rC-HapS was approximately 62% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with rC-HapS mixed with Freund's adjuvant in comparison with control groups. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after subcutaneous immunization in BALB/c mice (IgG2a/IgG1 < 1). The sera from rC-HapS immunized animals were strongly bactericidal against nontypeable Haemophilus influenzae. These results suggest that rC-HapS may be a potential vaccine candidate for nontypeable Haemophilus influenzae. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characteristics associated with seasonal influenza vaccination of preschool children--Oregon, 2006-2008.

PubMed

2011-07-29

Starting with the 2010-11 influenza season, the Advisory Committee on Immunization Practices (ACIP) recommended that all children aged ≥6 months be vaccinated against influenza annually, and that previously unvaccinated children aged ≤8 years be given 2 doses of vaccine. The American Academy of Pediatrics (AAP) also recommends influenza vaccinations for this population. Throughout influenza seasons, preschool children often have higher rates of influenza-related hospitalization than any other age group except older adults. To estimate influenza vaccination coverage and identify sociodemographic and health-care usage correlates of influenza vaccination status among children aged 2 years, data from the 2006-2008 Oregon Pregnancy Risk Assessment Monitoring Survey follow-back survey (Oregon PRAMS-2) were analyzed. This report summarizes the results. In Oregon, 37.7% of mothers reported that their children had received an influenza vaccination during the most recent influenza season. Factors positively associated with recent influenza vaccination in the multivariable-adjusted model were children's influenza vaccination in the previous year, children's receipt of all recommended immunizations, children's uninterrupted health insurance coverage, and mothers' unmarried status. The only factor negatively associated with vaccination was use of a family doctor rather than a pediatrician for well-child visits. The concern about vaccinations most commonly identified by mothers of children who had not received an influenza vaccination during the most recent influenza season (33.9%) was the opinion that too many shots are given at a time. This report highlights the need for health-care provider-based and community-based strategies to increase influenza vaccination coverage for children in Oregon.

Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus.

PubMed

Samarasinghe, Amali E; Melo, Rossana C N; Duan, Susu; LeMessurier, Kim S; Liedmann, Swantje; Surman, Sherri L; Lee, James J; Hurwitz, Julia L; Thomas, Paul G; McCullers, Jonathan A

2017-04-15

Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus-infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8 + T cell numbers in the airways. In vitro assays with primary or bone marrow-derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide-exposed eosinophils induced CD8 + T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity. Copyright © 2017 by The American Association of Immunologists, Inc.

Protection against avian influenza H9N2 virus challenge by immunization with hemagglutinin- or neuraminidase-expressing DNA in BALB/c mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu Meizhen; Fang Fang; Chen Yan

2006-05-19

Avian influenza viruses of H9N2 subtype are widely spread in avian species. The viruses have recently been transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. In this study, an avian influenza H9N2 virus strain (A/Chicken/Jiangsu/7/2002), isolated in Jiangsu Province, China, was used to infect BALB/c mice for adaptation. After five lung-to-lung passages, the virus was stably proliferated in a large quantity in the murine lung and caused the deaths of mice. In addition, we explored the protection induced by H9N2 virus hemagglutinin (HA)- and neuraminidase (NA)-expressing DNAs in BALB/c mice. Female BALB/c micemore » aged 6-8 weeks were immunized once or twice at a 3-week interval with HA-DNA and NA-DNA by electroporation, respectively, each at a dose of 3, 10 or 30 {mu}g. The mice were challenged with a lethal dose (40x LD{sub 5}) of influenza H9N2 virus four weeks after immunization once or one week after immunization twice. The protections of DNA vaccines were evaluated by the serum antibody titers, residual lung virus titers, and survival rates of the mice. The result showed that immunization once with not less than 10 {mu}g or twice with 3 {mu}g HA-DNA or NA-DNA provided effective protection against homologous avian influenza H9N2 virus.« less

Humoral immunity to influenza in an at-risk population and severe influenza cases in Russia in 2016-2017.

PubMed

Ilyicheva, Tatyana N; Durymanov, Alexander G; Svyatchenko, Svetlana V; Marchenko, Vasily Yu; Sobolev, Ivan A; Bakulina, Anastasiya Yu; Goncharova, Natalia I; Kolosova, Natalia P; Susloparov, Ivan M; Pyankova, Olga G; Ryzhikov, Alexander B; Maksyutov, Rinat A

2018-06-05

This work aimed to analyze the herd immunity to influenza among a Russian population living in regions with an increased risk of emergence of viruses with pandemic potential, and to isolate and investigate virus strains from severe influenza cases, including fatal cases, during the 2016-2017 epidemic season. In November 2016 - March 2017 highly pathogenic influenza outbreaks were registered in Russia among wild birds and poultry. No cases of human infection were registered. Analysis of 760 sera from people who had contact with infected or perished birds revealed the presence of antibodies to A(H5N1) virus of clade 2.3.2.1c and A(H5N8) virus of clade 2.3.4.4. The 2016-2017 influenza epidemic season in Russia began in weeks 46-47 of 2016 with predominant circulation of influenza A(H3N2) viruses. Strains isolated from severe influenza cases mainly belonged to 3C.2a.2 and 3C.2a.3 genetic groups. Up to the 8th week of 2017 severe influenza cases were often caused by influenza B viruses which belonged to 1A genetic group with antigenic properties similar to B/Brisbane/60/2008. All influenza A and B virus strains isolated in the 2016-2017 epidemic season were sensitive to oseltamivir and zanamivir.

Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection.

PubMed

Kwon, Ji-Sun; Yoon, Jungsoon; Kim, Yeon-Jung; Kang, Kyuho; Woo, Sunje; Jung, Dea-Im; Song, Man Ki; Kim, Eun-Ha; Kwon, Hyeok-Il; Choi, Young Ki; Kim, Jihye; Lee, Jeewon; Yoon, Yeup; Shin, Eui-Cheol; Youn, Jin-Won

2014-08-01

Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell-based vaccine, but the narrow breadth of T-cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T-cell immunodominance hierarchy in humans in an experimental setting, influenza-primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN-γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T-cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD50 challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP366 epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV-NP + PA showed improved protection. Taken together, a vaccinia-based influenza vaccine expressing conserved internal proteins improved the breadth of influenza-specific T-cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine.

PubMed

Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan; Xu, Jianqing

2012-01-01

A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations.

Trends in influenza vaccination coverage rates in South Korea from 2005 to 2014: Effect of public health policies on vaccination behavior.

PubMed

Seo, Jeongmin; Lim, Juwon

2018-05-05

Influenza is a major cause of morbidity and mortality worldwide. Annual vaccination is effective in its prevention and is recommended especially in susceptible populations such as the elderly over 65 years, children younger than 5, pregnant women, and people with chronic diseases. Overall, South Korea has a high vaccination rate owing to its National Immunization Program, although the method and extent of its coverage varies among the target subgroups. The aim of this study is to assess the trend of influenza vaccination coverage between 2005 and 2014 in South Korea to address the influence of sociodemographic and disease factors on vaccination behavior. Also, we aim to compare the vaccination coverage of target subgroups and evaluate the effect of relevant policies to provide suggestions for their improvement. A total of 61,036 respondents from the Korea National Health and Nutrition Examination Surveys III to VI were included. The total influenza vaccination coverage increased from 38.0% in 2005 to 44.1% in 2014. Vaccination coverage was higher among the elderly aged ≥65 years (range, 70.0-79.8%; p-for-trend <0.001) and children under 5 (range, 64.6-78.9%; p-for-trend < 0.001) than among pregnant women (range, 9.4-37.8%; p-for-trend = 0.122) and people with chronic diseases (range, 29.6-42.6%; p-for-trend = 0.068) from 2005 to 2014. High vaccination coverage was associated with female gender, rural residence, low education level, high income, and increasing number of chronic diseases. But the effect of high income on high vaccination coverage was absent in the elderly aged ≥65 years and children under 5. Influenza vaccination rates have steadily increased from 2005 to 2014 in South Korea. Disparities between target groups correspond to their financial coverage under the National Immunization Program, and financial aids remove the influence of high income on higher vaccination rates. Future vaccination policies should focus on pregnant women and people with chronic diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

The impact of personal experiences with infection and vaccination on behaviour-incidence dynamics of seasonal influenza.

PubMed

Wells, C R; Bauch, C T

2012-08-01

Personal experiences with past infection events, or perceived vaccine failures and complications, are known to drive vaccine uptake. We coupled a model of individual vaccinating decisions, influenced by these drivers, with a contact network model of influenza transmission dynamics. The impact of non-influenzal influenza-like illness (niILI) on decision-making was also incorporated: it was possible for individuals to mistake niILI for true influenza. Our objectives were to (1) evaluate the impact of personal experiences on vaccine coverage; (2) understand the impact of niILI on behaviour-incidence dynamics; (3) determine which factors influence vaccine coverage stability; and (4) determine whether vaccination strategies can become correlated on the network in the absence of social influence. We found that certain aspects of personal experience can significantly impact behaviour-incidence dynamics. For instance, longer term memory for past events had a strong stabilising effect on vaccine coverage dynamics, although it could either increase or decrease average vaccine coverage depending on whether memory of past infections or past vaccine failures dominated. When vaccine immunity wanes slowly, vaccine coverage is low and stable, and infection incidence is also very low, unless the effects of niILI are ignored. Strategy correlations can occur in the absence of imitation, on account of the neighbour-neighbour transmission of infection and history-dependent decision making. Finally, niILI weakens the behaviour-incidence coupling and therefore tends to stabilise dynamics, as well as breaking up strategy correlations. Behavioural feedbacks, and the quality of self-diagnosis of niILI, may need to be considered in future programs adopting "universal" flu vaccines conferring long-term immunity. Public health interventions that focus on reminding individuals about their previous influenza infections, as well as communicating facts about vaccine efficacy and the difference between influenza and niILI, may be an effective way to increase vaccine coverage and prevent unexpected drops in coverage. Copyright © 2012 Elsevier B.V. All rights reserved.

Tobacco Smoke Exposure and Altered Nasal Responses to Live Attenuated Influenza Virus

EPA Science Inventory

Background: Epidemiologic evidence links tobacco smoke and increased risk for influenza in humans, but the specific host defense pathways involved are unclear. Objective. Develop a model to examine influenza-induced innate immune responses in humans and test the hypothesis that ...

New Kids on the Block: RNA-Based Influenza Virus Vaccines.

PubMed

Scorza, Francesco Berlanda; Pardi, Norbert

2018-04-01

RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

Antibody Recognition of a Highly Conserved Influenza Virus Epitope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ekiert, Damian C.; Bhabha, Gira; Elsliger, Marc-André

2009-05-21

Influenza virus presents an important and persistent threat to public health worldwide, and current vaccines provide immunity to viral isolates similar to the vaccine strain. High-affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Cocrystal structures were determined at 2.2 and 2.7 angstrom resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to other structurally characterized influenza antibodies, CR6261 recognizes amore » highly conserved helical region in the membrane-proximal stem of HA1 and HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.« less

Intranasal administration of poly-gamma glutamate induced antiviral activity and protective immune responses against H1N1 influenza A virus infection.

PubMed

Kim, Eun-Ha; Choi, Young-Ki; Kim, Chul-Joong; Sung, Moon-Hee; Poo, Haryoung

2015-10-06

The global outbreak of a novel swine-origin strain of the 2009 H1N1 influenza A virus and the sudden, worldwide increase in oseltamivir-resistant H1N1 influenza A viruses highlight the urgent need for novel antiviral therapy. Here, we investigated the antiviral efficacy of poly-gamma glutamate (γ-PGA), a safe and edible biomaterial that is naturally synthesized by Bacillus subtilis, against A/Puerto Rico/8/1934 (PR8) and A/California/04/2009 (CA04) H1N1 influenza A virus infections in C57BL/6 mice. Intranasal administration of γ-PGA for 5 days post-infection improved survival, increased production of antiviral cytokines including interferon-beta (IFN-β) and interleukin-12 (IL-12), and enhanced activation of natural killer (NK) cells and influenza antigen-specific cytotoxic T lymphocytes (CTL) activity. These results suggest that γ-PGA protects mice against H1N1 influenza A virus by enhancing antiviral immune responses.

Evaluation of Influenza Prevention in the Workplace Using a Personally Controlled Health Record: Randomized Controlled Trial

PubMed Central

Simons, William W; Olson, Karen; Brownstein, John S; Mandl, Kenneth D

2008-01-01

Background Personally controlled health records (PCHRs) are accessible over the Internet and allow individuals to maintain and manage a secure copy of their medical data. These records provide a new opportunity to provide customized health recommendations to individuals based on their record content. Health promotion programs using PCHRs can potentially be used in a variety of settings and target a large range of health issues. Objectives The aim was to assess the value of a PCHR in an employee health promotion program for improving knowledge, beliefs, and behavior around influenza prevention. Methods We evaluated a PCHR-based employee health promotion program using a randomized controlled trial design. Employees at Hewlett Packard work sites who reported reliable Internet access and email use at least once every 2 days were recruited for participation. PCHRs were provided to all participants for survey administration, and tailored, targeted health messages on influenza illness and prevention were delivered to participants in the intervention group. Participants in the control group received messages addressing cardiovascular health and sun protection. The main outcome measure was improvement in knowledge, beliefs, and behavior around influenza prevention. Secondary outcomes were influenza vaccine rates among household members, the impact of cardiovascular health and sun protection messages on the control group, and the usability and utility of the PCHR-based program for employees. Results The intervention did not have a statistically significant effect on the influenza knowledge elements we assessed but did impact certain beliefs surrounding influenza. Participants in the intervention group were more likely to believe that the influenza vaccine was effective (OR = 5.6; 95% CI = 1.7-18.5), that there were actions they could take to prevent the flu (OR = 3.2; 95% CI = 1.1-9.2), and that the influenza vaccine was unlikely to cause a severe reaction (OR = 4.4; 95% CI = 1.3-15.3). Immunization rates did not differ between the intervention and control groups. However, participants in the intervention group were more likely to stay home during an infectious respiratory illness compared with participants in the control group (39% [16/41] vs 14% [5/35], respectively; P = .02). The program also succeeded in improving recognition of the signs of heart attack and stroke among participants in the control group. Overall, 78% of participants rated the PCHR as “extremely/very” easy to use, and 73% responded that they would be “extremely/very” likely to participate again in a PCHR-based health promotion system such as this one. Conclusions With a small sample size, this study identified a modest impact of a PCHR-based employee health program on influenza prevention and control. Employees found the PCHR acceptable and easy to use, suggesting that it should be explored as a common medium for health promotion in the workplace. Trial Registration ClinicalTrials.gov NCT00142077 PMID:18343794

Evaluation of influenza prevention in the workplace using a personally controlled health record: randomized controlled trial.

PubMed

Bourgeois, Florence T; Simons, William W; Olson, Karen; Brownstein, John S; Mandl, Kenneth D

2008-03-14

Personally controlled health records (PCHRs) are accessible over the Internet and allow individuals to maintain and manage a secure copy of their medical data. These records provide a new opportunity to provide customized health recommendations to individuals based on their record content. Health promotion programs using PCHRs can potentially be used in a variety of settings and target a large range of health issues. The aim was to assess the value of a PCHR in an employee health promotion program for improving knowledge, beliefs, and behavior around influenza prevention. We evaluated a PCHR-based employee health promotion program using a randomized controlled trial design. Employees at Hewlett Packard work sites who reported reliable Internet access and email use at least once every 2 days were recruited for participation. PCHRs were provided to all participants for survey administration, and tailored, targeted health messages on influenza illness and prevention were delivered to participants in the intervention group. Participants in the control group received messages addressing cardiovascular health and sun protection. The main outcome measure was improvement in knowledge, beliefs, and behavior around influenza prevention. Secondary outcomes were influenza vaccine rates among household members, the impact of cardiovascular health and sun protection messages on the control group, and the usability and utility of the PCHR-based program for employees. The intervention did not have a statistically significant effect on the influenza knowledge elements we assessed but did impact certain beliefs surrounding influenza. Participants in the intervention group were more likely to believe that the influenza vaccine was effective (OR = 5.6; 95% CI = 1.7-18.5), that there were actions they could take to prevent the flu (OR = 3.2; 95% CI = 1.1-9.2), and that the influenza vaccine was unlikely to cause a severe reaction (OR = 4.4; 95% CI = 1.3-15.3). Immunization rates did not differ between the intervention and control groups. However, participants in the intervention group were more likely to stay home during an infectious respiratory illness compared with participants in the control group (39% [16/41] vs 14% [5/35], respectively; P = .02). The program also succeeded in improving recognition of the signs of heart attack and stroke among participants in the control group. Overall, 78% of participants rated the PCHR as "extremely/very" easy to use, and 73% responded that they would be "extremely/very" likely to participate again in a PCHR-based health promotion system such as this one. With a small sample size, this study identified a modest impact of a PCHR-based employee health program on influenza prevention and control. Employees found the PCHR acceptable and easy to use, suggesting that it should be explored as a common medium for health promotion in the workplace. ClinicalTrials.gov NCT00142077.

Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy.

PubMed

Montoya, Carlos J; Toro, Maria F; Aguirre, Carlos; Bustamante, Alberto; Hernandez, Mariluz; Arango, Liliana P; Echeverry, Marta; Arango, Ana E; Prada, Maria C; Alarcon, Herminia del P; Rojas, Mauricio

2007-06-01

Given that highly active antiretroviral therapy (HAART) has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1)-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI) antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40) against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

Vaccine-specific antibody secreting cells are a robust early marker of LAIV-induced B-cell response in ferrets.

PubMed

Cherukuri, Anu; Servat, Esteban; Woo, Jennifer

2012-01-05

Currently, a robust set of immune correlates for live attenuated influenza vaccine (LAIV) efficacy in humans has not been fully elucidated. The serum hemagglutination inhibition (HAI) assay has been historically used to measure humoral immune responses to injectable inactivated influenza vaccination. However, serum antibody titers do not reliably reflect the complete mechanism of action of LAIV, which is an intranasally delivered vaccine and is expected to induce local mucosal and cellular immune responses in addition to humoral immune responses. Therefore, we designed a study to evaluate potential immune correlates of LAIV vaccination in the ferret animal model of influenza infection. Ferrets were vaccinated with increasing doses of LAIV and four weeks later challenged with a homologous wild-type (wt) H1N1 strain. Humoral immune responses measured following LAIV vaccination included HAI, serum antibodies and antibody secreting cells (ASC); and the responses were found to correlate with the dose level of LAIV administered in this model. Protection from wt virus challenge was determined by measuring inhibition of wt viral replication in nasal washes and in lung tissue. Results demonstrated that LAIV doses ≥ 5.0 log(10) Plaque Forming Units (PFU) elicited vaccine-specific IgG and IgA ASC frequencies and induced complete protection in the lungs. Further, we developed a novel model utilizing seropositive older ferrets to demonstrate that in the background of previous wt influenza infection LAIV induces a robust vaccine-specific B-cell response even in the absence of serum antibody response, a result that suggests that effector B-cell responses generated by LAIV are not inhibited by prior viral exposure. Finally, we demonstrated that LAIV elicits strain-specific memory B-cell responses that are measurable in a background of wt influenza infections. Taken together, results from these studies identified the antigen-specific ASC frequency as a useful early biomarker of LAIV-induced B-cell immune response. Copyright © 2011 Elsevier Ltd. All rights reserved.

Vitamin E, vitamin A and zinc status are not releated to serologic response to influenza vaccine in older adults: an observational prospective cohort study

USDA-ARS?s Scientific Manuscript database

It has been hypothesized that micronutrient levels play a role in the immune 2 response to vaccination. However, population-level research on the association between 3 micronutrient levels and immune response to influenza vaccination is needed. To determine whether serum vitamin A, vitamin E, or zin...

Seasonal Trivalent Inactivated Influenza Vaccine Protects against 1918 Spanish Influenza Virus Infection in Ferrets

PubMed Central

Pearce, Melissa B.; Belser, Jessica A.; Gustin, Kortney M.; Pappas, Claudia; Houser, Katherine V.; Sun, Xiangjie; Maines, Taronna R.; Pantin-Jackwood, Mary J.; Katz, Jacqueline M.

2012-01-01

The influenza virus H1N1 pandemic of 1918 was one of the worst medical catastrophes in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus [A(H1N1)pdm09], the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV), share cross-reactive antigenic determinants. In this study, we demonstrate that immunization with the 2010-2011 seasonal TIV induces neutralizing antibodies that cross-react with the reconstructed 1918 pandemic virus in ferrets. TIV-immunized ferrets subsequently challenged with the 1918 virus displayed significant reductions in fever, weight loss, and virus shedding compared to these parameters in nonimmune control ferrets. Seasonal TIV was also effective in protecting against the lung infection and severe lung pathology associated with 1918 virus infection. Our data demonstrate that prior immunization with contemporary TIV provides cross-protection against the 1918 virus in ferrets. These findings suggest that exposure to A(H1N1)pdm09 through immunization may provide protection against the reconstructed 1918 virus which, as a select agent, is considered to pose both biosafety and biosecurity threats. PMID:22553323

Delivery of GM-CSF to Protect against Influenza Pneumonia

PubMed Central

Subramaniam, Renuka; Hillberry, Zachary; Chen, Han; Feng, Yan; Fletcher, Kalyn; Neuenschwander, Pierre; Shams, Homayoun

2015-01-01

Background Since adaptive immunity is thought to be central to immunity against influenza A virus (IAV) pneumonias, preventive strategies have focused primarily on vaccines. However, vaccine efficacy has been variable, in part because of antigenic shift and drift in circulating influenza viruses. Recent studies have highlighted the importance of innate immunity in protecting against influenza. Methods Granulocyte-macrophage colony stimulating factor (GM-CSF) contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production. Results Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM). In this study, we report that pulmonary delivery of GM-CSF to wild type young and aged mice abrogated mortality from IAV. Conclusion We also demonstrate that protection is species specific and human GM-CSF do not protect the mice nor stimulates mouse immunity. We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection. PMID:25923215

Intramuscular and intranasal immunization with an H7N9 influenza virus-like particle vaccine protects mice against lethal influenza virus challenge.

PubMed

Ren, Zhiguang; Zhao, Yongkun; Liu, Jing; Ji, Xianliang; Meng, Lingnan; Wang, Tiecheng; Sun, Weiyang; Zhang, Kun; Sang, Xiaoyu; Yu, Zhijun; Li, Yuanguo; Feng, Na; Wang, Hualei; Yang, Songtao; Yang, Zhengyan; Ma, Yuanfang; Gao, Yuwei; Xia, Xianzhu

2018-05-01

The H7N9 influenza virus epidemic has been associated with a high mortality rate in China. Therefore, to prevent the H7N9 virus from causing further damage, developing a safe and effective vaccine is necessary. In this study, a vaccine candidate consisting of virus-like particles (VLPs) based on H7N9 A/Shanghai/2/2013 and containing hemagglutinin (HA), neuraminidase (NA), and matrix protein (M1) was successfully produced using a baculovirus (BV) expression system. Immunization experiments showed that strong humoral and cellular immune responses could be induced by the developed VLPs when administered via either the intramuscular (IM) or intranasal (IN) immunization routes. Notably, VLPs administered via both immunization routes provided 100% protection against lethal infection caused by the H7N9 virus. The IN immunization with 40μg of H7N9 VLPs induced strong lung IgA and lung tissue resident memory (TRM) cell-mediated local immune responses. These results provide evidence for the development of an effective preventive vaccine against the H7N9 virus based on VLPs administered through both the IM and IN immunization routes. Copyright © 2017. Published by Elsevier B.V.

A Portrait of the Sialyl Glycan Receptor Specificity of the H10 Influenza Virus Hemagglutinin—A Picture of an Avian Virus on the Verge of Becoming a Pandemic?

PubMed Central

Schneider, Elena K.; Li, Jian; Velkov, Tony

2017-01-01

Pandemic influenza is a constant global threat to human health. In particular, the pandemic potential of novel avian influenza viruses such as the H10N7 and H10N8 avian strains, which recently managed to cross the species barrier from birds to humans, are always of great concern as we are unlikely to have any prior immunity. Human and avian isolates of H10 influenza display the ability to rapidly adapt to replication in mammalian hosts. Fortunately, so far there is no evidence of efficient human-to-human transmission of any avian influenza virus. This review examines all of the available clinical and biological data for H10 influenza viruses with an emphasis on hemagglutinin as it is a major viral antigen that determines host range and immunity. The available glycan binding data on the influenza H10 hemagglutinin are discussed in a structure-recognition perspective. Importantly, this review raises the question of whether the emerging novel avian H10 influenza viruses truly represents a threat to global health that warrants close monitoring. PMID:29236069

Progress on adenovirus-vectored universal influenza vaccines.

PubMed

Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun

2015-01-01

Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8(+) T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides 'self-adjuvanting' activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches.

Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

PubMed Central

Sridhar, Saranya; Brokstad, Karl A.; Cox, Rebecca J.

2015-01-01

Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection. PMID:26343192

Development of a heat-stable and orally delivered recombinant M2e-expressing B. subtilis spore-based influenza vaccine.

PubMed

Zhao, Guangyu; Miao, Yu; Guo, Yan; Qiu, Hongjie; Sun, Shihui; Kou, Zhihua; Yu, Hong; Li, Junfeng; Chen, Yue; Jiang, Shibo; Du, Lanying; Zhou, Yusen

2014-01-01

Highly conserved ectodomain of influenza virus M2 protein (M2e) is an important target for the development of universal influenza vaccines. Today, the use of chemical or genetic fusion constructs have been undertaken to overcome the low immunogenicity of M2e in vaccine formulation. However, current M2e vaccines are neither orally delivered nor heat-stable. In this study, we evaluated the immune efficacy of an orally delivered recombinant M2e vaccine containing 3 molcules of M2e consensus sequence of influenza A viruses, termed RSM2e3. To accomplish this, CotB, a spore coat of Bacillus subtilis (B. subtilis), was used as a fusion partner, and heat-stable nonpathogenic B. subtilis spores were used as the carrier. Our results showed that CotB-M2e3 fusion had no effect on spore structure or function in the resultant recombinant RSM2e3 strain and that heterologous influenza virus M2e protein was successfully displayed on the surface of the recombinant RSM2e3 spore. Importantly, recombinant RSM2e3 spores elicited strong and long-term M2e-specific systemic and mucosal immune responses, completely protecting immunized mice from lethal challenge of A/PR/8/34(H1N1) influenza virus. Taken together, our study forms a solid basis for the development of a novel orally delivered and heat-stable influenza vaccine based on B. subtilis spore surface display.

Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection.

PubMed

Roy, Anirban; Bauer, Stephen M; Lawrence, B Paige

2012-01-01

Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host's ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection.

A single immunization with modified vaccinia virus Ankara-based influenza virus H7 vaccine affords protection in the influenza A(H7N9) pneumonia ferret model.

PubMed

Kreijtz, Joost H C M; Wiersma, Lidewij C M; De Gruyter, Heidi L M; Vogelzang-van Trierum, Stella E; van Amerongen, Geert; Stittelaar, Koert J; Fouchier, Ron A M; Osterhaus, Albert D M E; Sutter, Gerd; Rimmelzwaan, Guus F

2015-03-01

Since the first reports in early 2013, >440 human cases of infection with avian influenza A(H7N9) have been reported including 122 fatalities. After the isolation of the first A(H7N9) viruses, the nucleotide sequences became publically available. Based on the coding sequence of the influenza virus A/Shanghai/2/2013 hemagglutinin gene, a codon-optimized gene was synthesized and cloned into a recombinant modified vaccinia virus Ankara (MVA). This MVA-H7-Sh2 viral vector was used to immunize ferrets and proved to be immunogenic, even after a single immunization. Subsequently, ferrets were challenged with influenza virus A/Anhui/1/2013 via the intratracheal route. Unprotected animals that were mock vaccinated or received empty vector developed interstitial pneumonia characterized by a marked alveolitis, accompanied by loss of appetite, weight loss, and heavy breathing. In contrast, animals vaccinated with MVA-H7-Sh2 were protected from severe disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines

PubMed Central

Banchereau, Romain; Baldwin, Nicole; Cepika, Alma-Martina; Athale, Shruti; Xue, Yaming; Yu, Chun I; Metang, Patrick; Cheruku, Abhilasha; Berthier, Isabelle; Gayet, Ingrid; Wang, Yuanyuan; Ohouo, Marina; Snipes, LuAnn; Xu, Hui; Obermoser, Gerlinde; Blankenship, Derek; Oh, Sangkon; Ramilo, Octavio; Chaussabel, Damien; Banchereau, Jacques; Palucka, Karolina; Pascual, Virginia

2014-01-01

The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines. PMID:25335753

[Attitudes and practices towards seasonal influenza vaccination amongst French hospital staff].

PubMed

Maurette, Max; Pinzelli, Pierre; Yordanov Sandev, Aleksandar; Nock, Francis

2017-04-27

This survey intends to describe the attitudes towards vaccination amongst the hospital staff in the region of Castres, in the south-west of France, and their influenza vaccination coverage. A questionnaire was attached to all pay slips in March 2014 and 471 questionnaires were completed (return rate: 22.4%). Seasonal influenza vaccination coverage rate was similar to that reported in other French surveys. Paramedical personnel were less commonly immunized against influenza compared to medical personnel and age was the major factor associated with vaccination. Three quarters of the non-immunized hospital personnel did not wish to be vaccinated against influenza. Nearly 50% of respondents believed that healthcare personnel do not have to be role models regarding vaccination. The arguments considered most compelling in favour of vaccination are protection of the family, then patient protection and finally protection of other staff members. A demand for accurate scientific information was expressed by respondents, preferably delivered at their workplace.

Modelling the impact of vaccination on curtailing Haemophilus influenzae serotype 'a'.

PubMed

Konini, Angjelina; Moghadas, Seyed M

2015-12-21

Haemophilus influenzae serotype a (Hia) is a human-restricted bacterial pathogen transmitted via direct contacts with an infectious individual. Currently, there is no vaccine available for prevention of Hia, and the disease is treated with antibiotics upon diagnosis. With ongoing efforts for the development of an anti-Hia protein-polysaccharide conjugated vaccine, we sought to investigate the effect of vaccination on curtailing Hia infection. We present the first stochastic model of Hia transmission and control dynamics, and parameterize it using available estimates in the literature. Since both naturally acquired and vaccine-induced immunity wane with time, model simulations show three important results. First, vaccination of only newborns cannot eliminate the pathogen from the population, even when a booster program is implemented with a high coverage. Second, achieving and maintaining a sufficiently high level of herd immunity for pathogen elimination requires vaccination of susceptible individuals in addition to a high vaccination coverage of newborns. Third, for a low vaccination rate of susceptible individuals, a high coverage of booster dose may be needed to raise the level of herd immunity for Hia eradication. Our findings highlight the importance of vaccination and timely boosting of the individual׳s immunity within the expected duration of vaccine-induced protection against Hia. When an anti-Hia vaccine becomes available, enhanced surveillance of Hia incidence and herd immunity could help determine vaccination rates and timelines for booster doses necessary to eliminate Hia from affected populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immune mechanisms associated with enhanced influenza A virus disease versus cross-protection in vaccinated pigs.

USDA-ARS?s Scientific Manuscript database

Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of cross-reactive, non-neutralizing antibody to the challenge I...

Granzyme B ELISPOT assay to measure influenza-specific cellular immunity.

PubMed

Salk, Hannah M; Haralambieva, Iana H; Ovsyannikova, Inna G; Goergen, Krista M; Poland, Gregory A

2013-12-15

The immunogenicity and efficacy of influenza vaccination are markedly lower in the elderly. Granzyme B (GrzB), quantified in fresh cell lysates, has been suggested to be a marker of cytotoxic T lymphocyte (CTL) response and a predictor of influenza illness among vaccinated older individuals. We have developed an influenza-specific GrzB ELISPOT assay using cryopreserved PBMCs. This method was tested on 106 healthy older subjects (ages 50-74) at baseline (Day 0) and three additional time points post-vaccination (Day 3, Day 28, Day 75) with influenza A/H1N1-containing vaccine. No significant difference was seen in GrzB response between any of the time points, although influenza-specific GrzB response appears to be elevated at all post-vaccination time points. There was no correlation between GrzB response and hemagglutination inhibition (HAI) titers, indicating no relationship between the cytolytic activity and humoral antibody levels in this cohort. Additionally, a significant negative correlation between GrzB response and age was observed. These results reveal a reduction in influenza-specific GrzB response as one ages. In conclusion, we have developed and optimized an influenza-specific ELISPOT assay for use with frozen cells to quantify the CTL-specific serine protease GrzB, as a measure of cellular immunity after influenza vaccination. © 2013.

A Bivalent Heterologous DNA Virus-Like-Particle Prime-Boost Vaccine Elicits Broad Protection against both Group 1 and 2 Influenza A Viruses

PubMed Central

Jiang, Wenbo; Wang, Shuangshuang; Chen, Honglin; Ren, Huanhuan; Huang, Xun; Wang, Guiqin; Chen, Ling; Chen, Zhiwei

2017-01-01

ABSTRACT Current seasonal influenza vaccines are efficacious when vaccine strains are matched with circulating strains. However, they do not protect antigenic variants and newly emerging pandemic and outbreak strains. Thus, there is a critical need for developing so-called “universal” vaccines that protect against all influenza viruses. In the present study, we developed a bivalent heterologous DNA virus-like particle prime-boost vaccine strategy. We show that mice immunized with this vaccine were broadly protected against lethal challenge from group 1 (H1, H5, and H9) and group 2 (H3 and H7) viruses, with 94% aggregate survival. To determine the immune correlates of protection, we performed passive immunizations and in vitro assays. We show that this vaccine elicited antibody responses that bound HA from group 1 (H1, H2, H5, H6, H8, H9, H11, and H12) and group 2 (H3, H4, H7, H10, H14, and H15) and neutralized homologous and intrasubtypic H5 and H7 and heterosubtypic H1 viruses and hemagglutinin-specific CD4 and CD8 T cell responses. As a result, passive immunization with immune sera fully protected mice against H5, H7, and H1 challenge, whereas with both immune sera and T cells the mice survived heterosubtypic H3 and H9 challenge. Thus, it appears that (i) neutralizing antibodies alone fully protect against homologous and intrasubtypic H5 and H7 and (ii) neutralizing and binding antibodies are sufficient to protect against heterosubtypic H1, (iii) but against heterosubtypic H3 and H9, binding antibodies and T cells are required for complete survival. We believe that this vaccine regimen could potentially be a candidate for a “universal” influenza vaccine. IMPORTANCE Influenza virus infection is global health problem. Current seasonal influenza vaccines are efficacious only when vaccine strains are matched with circulating strains. However, these vaccines do not protect antigenic variants and newly emerging pandemic and outbreak strains. Because of this, there is an urgent need to develop so-called “universal” influenza vaccines that can protect against both current and future influenza strains. In the present study, we developed a bivalent heterologous prime-boost vaccine strategy. We show that a bivalent vaccine regimen elicited broad binding and neutralizing antibody and T cell responses that conferred broad protection against diverse challenge viruses in mice, suggesting that this bivalent prime-boost strategy could practically be a candidate for a “universal” influenza vaccine. PMID:28179535

Evaluation of the immunogenicity and safety of different doses and formulations of a broad spectrum influenza vaccine (FLU-v) developed by SEEK: study protocol for a single-center, randomized, double-blind and placebo-controlled clinical phase IIb trial.

PubMed

van Doorn, Eva; Pleguezuelos, Olga; Liu, Heng; Fernandez, Ana; Bannister, Robin; Stoloff, Gregory; Oftung, Fredrik; Norley, Stephen; Huckriede, Anke; Frijlink, Henderik W; Hak, Eelko

2017-04-04

Current influenza vaccines, based on antibodies against surface antigens, are unable to provide protection against newly emerging virus strains which differ from the vaccine strains. Therefore the population has to be re-vaccinated annually. It is thus important to develop vaccines which induce protective immunity to a broad spectrum of influenza viruses. This trial is designed to evaluate the immunogenicity and safety of FLU-v, a vaccine composed of four synthetic peptides with conserved epitopes from influenza A and B strains expected to elicit both cell mediated immunity (CMI) and humoral immunity providing protection against a broad spectrum of influenza viruses. In a single-center, randomized, double-blind and placebo-controlled phase IIb trial, 222 healthy volunteers aged 18-60 years will be randomized (2:2:1:1) to receive two injections of a suspension of 500 μg FLU-v in saline (arm 1), one dose of emulsified 500 μg FLU-v in Montanide ISA-51 and water for injection (WFI) followed by one saline dose (arm 2), two saline doses (arm 3), or one dose of Montanide ISA-51 and WFI emulsion followed by one saline dose (arm 4). All injections will be given subcutaneously. Primary endpoints are safety and FLU-v induced CMI, evaluated by cytokine production by antigen specific T cell populations (flow-cytometry and ELISA). Secondary outcomes are measurements of antibody responses (ELISA and multiplex), whereas exploratory outcomes include clinical efficacy and additional CMI assays (ELISpot) to show cross-reactivity. Broadly protective influenza vaccines able to provide protection against multiple strains of influenza are urgently needed. FLU-v is a promising vaccine which has shown to trigger the cell-mediated immune response. The dosages and formulations tested in this current trial are also estimated to induce antibody response. Therefore, both cellular and humoral immune responses will be evaluated. EudraCT number 2015-001932-38 ; retrospectively registered clinicaltrials.gov NCT02962908 (November 7th 2016).

Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic.

PubMed

Lo, Chia-Yun; Strobl, Susan L; Dunham, Kimberly; Wang, Wei; Stewart, Lucy; Misplon, Julia A; Garcia, Mayra; Gao, Jin; Ozawa, Tatsuhiko; Price, Graeme E; Navidad, Jose; Gradus, Steve; Bhattacharyya, Sanjib; Viboud, Cecile; Eichelberger, Maryna C; Weiss, Carol D; Gorski, Jack; Epstein, Suzanne L

2017-01-01

Antibody and T-cell immunity to conserved influenza virus antigens can protect animals against infection with diverse influenza strains. Although immunity against conserved antigens occurs in humans, whether such responses provide cross-protection in humans and could be harnessed as the basis for universal influenza vaccines is controversial. The 2009 pandemic provided an opportunity to investigate whether pre-existing cross-reactive immunity affected susceptibility to infection. In 2009, we banked sera and peripheral blood mononuclear cells (PBMC) from blood donors, then monitored them for pandemic influenza infection (pH1N1) by polymerase chain reaction or seroconversion. Antibodies to hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix 2 (M2), and HA-pseudotypes were measured in sera. T-cell inteferon-γ enzyme-linked immunospot responses were measured in PBMC. There were 13 infections in 117 evaluable donors. Pre-existing T-cell reactivity to pH1N1 was substantial (of 153 donors tested, 146 had >100 spot-forming cells/10 6 cells). Antibodies reactive with pH1N1 were common: anti-NP (all donors) and anti-M2 (44% of donors). Pseudotype-neutralizing antibodies to H1 were detected, but not to highly conserved HA epitopes. Unexpectedly, donors with symptomatic pH1N1 infection had sharp rises in HA pseudotype-neutralizing antibodies, not only pH1N1 but also against multiple seasonal H1s. In addition, an exploratory study of a T-cell marker (response to NP 418-426 ) identified probable infection missed by standard criteria. Although the number of infections was inadequate for conclusions about mechanisms of protection, this study documents the wide variety of pre-existing, cross-reactive, humoral and cellular immune responses to pandemic influenza virus antigens in humans. These responses can be compared with results of other studies and explored in universal influenza vaccine studies. Published by Oxford University Press on behalf of Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Modelling the effects of booster dose vaccination schedules and recommendations for public health immunization programs: the case of Haemophilus influenzae serotype b.

PubMed

Charania, Nadia A; Moghadas, Seyed M

2017-09-13

Haemophilus influenzae serotype b (Hib) has yet to be eliminated despite the implementation of routine infant immunization programs. There is no consensus regarding the number of primary vaccine doses and an optimal schedule for the booster dose. We sought to evaluate the effect of a booster dose after receiving the primary series on the long-term disease incidence. A stochastic model of Hib transmission dynamics was constructed to compare the long-term impact of a booster vaccination and different booster schedules after receiving the primary series on the incidence of carriage and symptomatic disease. We parameterized the model with available estimates for the efficacy of Hib conjugate vaccine and durations of both vaccine-induced and naturally acquired immunity. We found that administering a booster dose substantially reduced the population burden of Hib disease compared to the scenario of only receiving the primary series. Comparing the schedules, the incidence of carriage for a 2-year delay (on average) in booster vaccination was comparable or lower than that observed for the scenario of booster dose within 1 year after primary series. The temporal reduction of symptomatic disease was similar in the two booster schedules, suggesting no superiority of one schedule over the other in terms of reducing the incidence of symptomatic disease. The findings underscore the importance of a booster vaccination for continued decline of Hib incidence. When the primary series provides a high level of protection temporarily, delaying the booster dose (still within the average duration of protection conferred by the primary series) may be beneficial to maintain longer-term protection levels and decelerate the decline of herd immunity in the population.

Haemophilus influenzae type b (Hib) vaccine: an effective control strategy in India.

PubMed

Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj; Bairwa, Mohan; Prinja, Shankar; Rajput, Meena

2011-11-01

Haemophilus influenzae type b (Hib) is an encapsulated, non-motile and non-spore-forming Gram-negative coccobacillus which causes severe pneumonia, meningitis and other life threatening illnesses. Hib disease affects almost exclusively (95%) children aged less than 5 years throughout the world. The mean age of onset is 6-24 months after which it declines gradually until age 5 years. The World Health Organization (WHO) estimates that Hib is responsible for 3 million cases of serious illnesses and approximately 386,000 deaths worldwide each year in children aged under 5 years. In the latest position paper on Hib vaccine, WHO recommended the inclusion of Hib conjugate vaccines in all routine infant immunization programs without waiting for local disease-burden data. The WHO and the Global Alliance for Vaccine Immunization (GAVI) have been working to expand supplies of Hib vaccine, reduce vaccine cost, and assist especially low-income countries with vaccine introduction. Hib vaccine is safe, highly effective and readily available in the market. Hib vaccine has been shown to be > 95% efficacious in diverse populations around the world. Globally, hundreds of millions of doses of Hib vaccine have been administered in the last 2 decades. More than 160 countries are using Hib vaccine in national immunization programmes and around 25 countries planning to introduce. Hib vaccination fits into the India's national immunization schedule.

77 FR 58843 - Advisory Committee on Immunization Practices (ACIP)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-24

..., hepatitis B vaccine, meningococcal vaccines, influenza, measles-mumps-rubella vaccine, pertussis and vaccine...-rubella vaccine, hepatitis B vaccine, child/adolescent immunization schedule, and the adult immunization...

Microneedle delivery of trivalent influenza vaccine to the skin induces long-term cross-protection.

PubMed

Kim, Yeu-Chun; Lee, Su-Hwa; Choi, Won-Hyung; Choi, Hyo-Jick; Goo, Tae-Won; Lee, Ju-Hie; Quan, Fu-Shi

2016-12-01

A painless self-immunization method with effective and broad cross-protection is urgently needed to prevent infections against newly emerging influenza viruses. In this study, we investigated the cross-protection efficacy of trivalent influenza vaccine containing inactivated A/PR/8/34 (H1N1), A/Hong Kong/68 (H3N2) and B/Lee/40 after skin vaccination using microneedle patches coated with this vaccine. Microneedle vaccination of mice in the skin provided 100% protection against lethal challenges with heterologous pandemic strain influenza A/California/04/09, heterogeneous A/Philippines/2/82 and B/Victoria/287 viruses 8 months after boost immunization. Cross-reactive serum IgG antibody responses against heterologous influenza viruses A/California/04/09, A/Philippines/2/82 and B/Victoria/287 were induced at high levels. Hemagglutination inhibition titers were also maintained at high levels against these heterogeneous viruses. Microneedle vaccination induced substantial levels of cross-reactive IgG antibody responses in the lung and cellular immune responses, as well as cross-reactive antibody-secreting plasma cells in the spleen. Viral loads in the lung were significantly (p < 0.05) reduced. All mice survived after viral challenges. These results indicate that skin vaccination with trivalent vaccine using a microneedle array could provide protection against seasonal epidemic or new pandemic strain of influenza viruses.

Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

PubMed Central

Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

2015-01-01

Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

Dietary lactosucrose suppresses influenza A (H1N1) virus infection in mice

PubMed Central

KISHINO, Eriko; TAKEMURA, Naho; MASAKI, Hisaharu; ITO, Tetsuya; NAKAZAWA, Masatoshi

2015-01-01

This study examined the effects of lactosucrose (4G-β-D-galactosylsucrose) on influenza A virus infections in mice. First, the effects of lactosucrose on fermentation in the cecum and on immune function were investigated. In female BALB/c mice, lactosucrose supplementation for 6 weeks promoted cecal fermentation and increased both secretory IgA (SIgA) levels in feces and total IgA and IgG2a concentrations in serum. Both the percentage of CD4+ T cells in Peyer’s patches and the cytotoxic activity of splenic natural killer (NK) cells increased significantly in response to lactosucrose. Next, we examined the effects of lactosucrose on low-dose influenza A virus infection in mice. After 2 weeks of dietary supplementation with lactosucrose, the mice were infected with low-dose influenza A virus. At 7 days post infection, a comparison with control mice showed that weight loss was suppressed, as were viral titers in the lungs. In the spleens of lactosucrose-fed mice, there was an increase in the percentage of NK cells. Lastly, mice fed lactosucrose were challenged with a lethal dose of influenza A virus. The survival rate of these mice was significantly higher than that of mice fed a control diet. These results suggested that lactosucrose supplementation suppresses influenza A virus infection by augmenting innate immune responses and enhancing cellular and mucosal immunity. PMID:26594606

78 FR 27392 - Advisory Committee on Immunization Practices (ACIP)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-10

... discussions on: General recommendations, influenza, Japanese encephalitis vaccine, pertussis vaccine, Herpes... votes are scheduled for influenza and Japanese encephalitis vaccine. Time will be available for public...

Previous exposure to homo- or heterosubtypic low pathogenic avian influenza protects mallards from infection against H5N8 HPAI clade 2.3.4.4

USDA-ARS?s Scientific Manuscript database

Mallard ducks are widely recognized as reservoirs for low pathogenic avian influenza viruses (AIV) in nature and differences in prevalence of viral subtypes are likely influenced by flock immunity in these birds. Heterosubtypic immunity (HSI) refers to the ability of one subtype of AIV to protect ag...

Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination.

PubMed

Díez-Domingo, Javier; Baldó, José-María; Planelles-Catarino, Maria Victoria; Garcés-Sánchez, María; Ubeda, Isabel; Jubert-Rosich, Angels; Marès, Josep; Garcia-Corbeira, Pilar; Moris, Philippe; Teko, Maurice; Vanden Abeele, Carline; Gillard, Paul

2015-03-01

An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3-9 years. In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3-9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03A or AS03B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. (NCT00502593). The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4(+) T cells with a TH 1 profile were observed. Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Budget impact analysis of vaccination against Haemophilus influenzae type b as a part of a Pentavalent vaccine in the childhood immunization schedule of Iran.

PubMed

Teimouri, Fatemeh; Kebriaeezadeh, Abbas; Zahraei, Seyed Mohsen; Gheiratian, MohammadMahdi; Nikfar, Shekoufeh

2017-01-14

Health decision makers need to know the impact of the development of a new intervention on the public health and health care costs so that they can plan for economic and financial objectives. The aim of this study was to determine the budget impact of adding Haemophilus influenzae type b (Hib) as a part of a Pentavalent vaccine (Hib-HBV-DTP) to the national childhood immunization schedule of Iran. An excel-based model was developed to determine the costs of including the Pentavalent vaccine in the national immunization program (NIP), comparing the present schedule with the previous one (including separate DTP and hepatitis B vaccines). The total annual costs included the cost of vaccination (the vaccine and syringe) and the cost of Hib treatment. The health outcome was the estimated annual cases of the diseases. The net budget impact was the difference in the total annual cost between the two schedules. Uncertainty about the vaccine effectiveness, vaccination coverage, cost of the vaccine, and cost of the diseases were handled through scenario analysis. The total cost of vaccination during 5 years was $18,060,463 in the previous program and $67,774,786 in the present program. Inclusion of the Pentavalent vaccine would increase the vaccination cost about $49 million, but would save approximately $6 million in the healthcare costs due to reduction of disease cases and treatment costs. The introduction of the Pentavalent vaccine resulted in a net increase in the healthcare budget expenditure across all scenarios from $43.4 million to $50.7 million. The results of this study showed that the inclusion of the Pentavalent vaccine in the NIP of Iran had a significant impact on the health care budget and increased the financial burden on the government. Budget impact of including Pentavalent vaccine in the national immunization schedule of Iranᅟ.

Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

PubMed Central

Soboleski, Mark R.; Gabbard, Jon D.; Price, Graeme E.; Misplon, Julia A.; Lo, Chia-Yun; Perez, Daniel R.; Ye, Jianqiang; Tompkins, S. Mark; Epstein, Suzanne L.

2011-01-01

Background The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. Methodology/Principal Findings BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. Conclusion/Significance Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic. PMID:21789196

Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans

PubMed Central

Borggren, Marie; Nielsen, Jens; Bragstad, Karoline; Karlsson, Ingrid; Krog, Jesper S; Williams, James A; Fomsgaard, Anders

2015-01-01

The threat posed by the 2009 pandemic H1N1 virus emphasized the need for new influenza A virus vaccines inducing a broad cross-protective immune response for use in both humans and pigs. An effective and broad influenza vaccine for pigs would greatly benefit the pork industry and contribute to public health by diminishing the risk of emerging highly pathogenic reassortants. Current inactivated protein vaccines against swine influenza produce only short-lived immunity and have no efficacy against heterologous strains. DNA vaccines are a potential alternative with advantages such as the induction of cellular and humoral immunity, inherent safety and rapid production time. We have previously developed a DNA vaccine encoding selected influenza proteins of pandemic origin and demonstrated broad protective immune responses in ferrets and pigs. In this study, we evaluated our DNA vaccine expressed by next-generation vectors. These new vectors can improve gene expression, but they are also efficiently produced on large scales and comply with regulatory guidelines by avoiding antibiotic resistance genes. In addition, a new needle-free delivery of the vaccine, convenient for mass vaccinations, was compared with intradermal needle injection followed by electroporation. We report that when our DNA vaccine is expressed by the new vectors and delivered to the skin with the needle-free device in the rabbit model, it can elicit an antibody response with the same titers as a conventional vector with intradermal electroporation. The needle-free delivery is already in use for traditional protein vaccines in pigs but should be considered as a practical alternative for the mass administration of broadly protective influenza DNA vaccines. PMID:25746201

Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

PubMed

Halasa, Natasha B; Gerber, Michael A; Berry, Andrea A; Anderson, Edwin L; Winokur, Patricia; Keyserling, Harry; Eckard, Allison Ross; Hill, Heather; Wolff, Mark C; McNeal, Monica M; Edwards, Kathryn M; Bernstein, David I

2015-09-01

Children 6 through 35 months of age are recommended to receive half the dose of influenza vaccine compared with older children and adults. This was a 6-site, randomized 2:1, double-blind study comparing full-dose (0.5 mL) trivalent inactivated influenza vaccine (TIV) with half-dose (0.25 mL) TIV in children 6 through 35 months of age. Children previously immunized with influenza vaccine (primed cohort) received 1 dose, and those with no previous influenza immunizations (naive cohort) received 2 doses of TIV. Local and systemic adverse events were recorded. Sera were collected before immunization and 1 month after last dose of TIV. Hemagglutination inhibition antibody testing was performed. Of the 243 subjects enrolled (32 primed, 211 naive), data for 232 were available for complete analysis. No significant differences in local or systemic reactions were observed. Few significant differences in immunogenicity to the 3 vaccine antigens were noted. The immune response to H1N1 was significantly higher in the full-dose group among primed subjects. In the naive cohort, the geometric mean titer for all 3 antigens after 2 doses of TIV were significantly higher in the 12 through 35 months compared with the 6 through 11 months age group. Our study confirms the safety of full-dose TIV given to children 6 through 35 months of age. An increase in antibody responses after full- versus half-dose TIV was not observed, except for H1N1 in the primed group. Larger studies are needed to clarify the potential for improved immunogenicity with higher vaccine doses. Recommending the same dose could simplify the production, storage, and administration of influenza vaccines.

School-located Influenza Vaccinations for Adolescents: A Randomized Controlled Trial.

PubMed

Szilagyi, Peter G; Schaffer, Stanley; Rand, Cynthia M; Goldstein, Nicolas P N; Vincelli, Phyllis; Hightower, A Dirk; Younge, Mary; Eagan, Ashley; Blumkin, Aaron; Albertin, Christina S; DiBitetto, Kristine; Yoo, Byung-Kwang; Humiston, Sharon G

2018-02-01

We aimed to evaluate the effect of school-located influenza vaccination (SLIV) on adolescents' influenza vaccination rates. In 2015-2016, we performed a cluster-randomized trial of adolescent SLIV in middle/high schools. We selected 10 pairs of schools (identical grades within pairs) and randomly allocated schools within pairs to SLIV or usual care control. At eight suburban SLIV schools, we sent parents e-mail notifications about upcoming SLIV clinics and promoted online immunization consent. At two urban SLIV schools, we sent parents (via student backpack fliers) paper immunization consent forms and information about SLIV. E-mails were unavailable at these schools. Local health department nurses administered nasal or injectable influenza vaccine at dedicated SLIV clinics and billed insurers. We compared influenza vaccination rates at SLIV versus control schools using school directories to identify the student sample in each school. We used the state immunization registry to determine receipt of influenza vaccination. The final sample comprised 17,650 students enrolled in the 20 schools. Adolescents at suburban SLIV schools had higher overall influenza vaccination rates than did adolescents at control schools (51% vs. 46%, p < .001; adjusted odds ratio = 1.27, 95% confidence interval 1.18-1.38, controlling for vaccination during the prior two seasons). No effect of SLIV was noted among urbanschools on multivariate analysis. SLIV did not substitute for vaccinations in primary care or other settings; in suburban settings, SLIV was associated with increased vaccinations in primary care or other settings (adjusted odds ratio = 1.10, 95% confidence interval 1.02-1.19). SLIV in this community increased influenza vaccination rates among adolescents attending suburban schools. Copyright © 2018. Published by Elsevier Inc.

Comparison of mucosal lining fluid sampling methods and influenza-specific IgA detection assays for use in human studies of influenza immunity.

PubMed

de Silva, Thushan I; Gould, Victoria; Mohammed, Nuredin I; Cope, Alethea; Meijer, Adam; Zutt, Ilse; Reimerink, Johan; Kampmann, Beate; Hoschler, Katja; Zambon, Maria; Tregoning, John S

2017-10-01

We need greater understanding of the mechanisms underlying protection against influenza virus to develop more effective vaccines. To do this, we need better, more reproducible methods of sampling the nasal mucosa. The aim of the current study was to compare levels of influenza virus A subtype-specific IgA collected using three different methods of nasal sampling. Samples were collected from healthy adult volunteers before and after LAIV immunization by nasal wash, flocked swabs and Synthetic Absorptive Matrix (SAM) strips. Influenza A virus subtype-specific IgA levels were measured by haemagglutinin binding ELISA or haemagglutinin binding microarray and the functional response was assessed by microneutralization. Nasosorption using SAM strips lead to the recovery of a more concentrated sample of material, with a significantly higher level of total and influenza H1-specific IgA. However, an equivalent percentage of specific IgA was observed with all sampling methods when normalized to the total IgA. Responses measured using a recently developed antibody microarray platform, which allows evaluation of binding to multiple influenza strains simultaneously with small sample volumes, were compared to ELISA. There was a good correlation between ELISA and microarray values. Material recovered from SAM strips was weakly neutralizing when used in an in vitro assay, with a modest correlation between the level of IgA measured by ELISA and neutralization, but a greater correlation between microarray-measured IgA and neutralizing activity. In conclusion we have tested three different methods of nasal sampling and show that flocked swabs and novel SAM strips are appropriate alternatives to traditional nasal washes for assessment of mucosal influenza humoral immunity. Copyright © 2017 Elsevier B.V. All rights reserved.

Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses

PubMed Central

McCormick, Kara; Jiang, Zhiyong; Zhu, Longchao; Lawson, Steven R.; Langenhorst, Robert; Ransburgh, Russell; Brunick, Colin; Tracy, Miranda C.; Hurtig, Heather R.; Mabee, Leah M.; Mingo, Mark; Li, Yanhua; Webby, Richard J.

2015-01-01

Background and Objectives Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes. Methods and Results Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates. Conclusion This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines. PMID:26061265

[Intestinal disorder of anaerobic bacteria aggravates pulmonary immune pathological injury of mice infected with influenza virus].

PubMed

Wu, Sha; Yan, Yuqi; Zhang, Mengyuan; Shi, Shanshan; Jiang, Zhenyou

2016-04-01

To investigate the relationship between the intestinal disorder of anaerobic bacteria and influenza virus infection, and the effect on pulmonary inflammatory cytokines in mice. Totally 36 mice were randomly divided into normal control group, virus-infected group and metronidazole treatment group (12 mice in each group). Mice in the metronidazole group were administrated orally with metronidazole sulfate for 8 days causing anaerobic bacteria flora imbalance; then all groups except the normal control group were treated transnasally with influenza virus (50 μL/d FM1) for 4 days to establish the influenza virus-infected models. Their mental state and lung index were observed, and the pathological morphological changes of lung tissues, caecum and intestinal mucosa were examined by HE staining. The levels of interleukin 4 (IL-4), interferon γ (IFN-γ), IL-10 and IL-17 in the lung homogenates were determined by ELISA. Compared with the virus control group, the metronidazole group showed obviously increased lung index and more serious pathological changes of the lung tissue and appendix inflammation performance. After infected by the FM1 influenza virus, IFN-γ and IL-17 of the metronidazole group decreased significantly and IL-4 and IL-10 levels were raised, but there was no statistically difference between the metronidazole and virus control groups. Intestinal anaerobic bacteria may inhibit the adaptive immune response in the lungs of mice infected with FM1 influenza virus through adjusting the lung inflammatory factors, affect the replication and clean-up time of the FM1 influenza virus, thus further aggravating pulmonary immune pathological injury caused by the influenza virus infection.

A novel approach for preparation of the antisera reagent for potency determination of inactivated H7N9 influenza vaccines.

PubMed

Schmeisser, Falko; Jing, Xianghong; Joshi, Manju; Vasudevan, Anupama; Soto, Jackeline; Li, Xing; Choudhary, Anil; Baichoo, Noel; Resnick, Josephine; Ye, Zhiping; McCormick, William; Weir, Jerry P

2016-03-01

The potency of inactivated influenza vaccines is determined using a single-radial immunodiffusion (SRID) assay and requires standardized reagents consisting of a Reference Antigen and an influenza strain-specific antiserum. Timely availability of reagents is a critical step in influenza vaccine production, and the need for backup approaches for reagent preparation is an important component of pandemic preparedness. When novel H7N9 viruses emerged in China in 2013, candidate inactivated H7N9 influenza vaccines were developed for evaluation in clinical trials, and reagents were needed to measure vaccine potency. We previously described an alternative approach for generating strain-specific potency antisera, utilizing modified vaccinia virus Ankara vectors to produce influenza hemagglutinin (HA)-containing virus-like particles (VLPs) for immunization. Vector-produced HA antigen is not dependent upon the success of the traditional bromelain-digestion and HA purification. Antiserum for H7N9 vaccines, produced after immunization of sheep with preparations of bromelain-HA (br-HA), was not optimal for the SRID assay, and the supply of antiserum was limited. However, antiserum obtained from sheep boosted with VLPs containing H7 HA greatly improved the ring quality in the SRID assay. Importantly, this antiserum worked well with both egg- and cell-derived antigen and was distributed to vaccine manufacturers. Utilizing a previously developed approach for preparing vaccine potency antiserum, we have addressed a major bottleneck encountered in preparation of H7N9 vaccine reagents. The combination of br-HA and mammalian VLPs for sequential immunization represents the first use of an alternative approach for producing an influenza vaccine potency antiserum. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Identifying children with chronic conditions for influenza vaccination using a statewide immunization registry: initial experiences of primary care providers.

PubMed

Clark, Sarah J; Lamarand, Kara; Dombkowski, Kevin J

2012-01-01

Children with chronic medical conditions are at increased risk of complications from influenza, yet their vaccination rates are low. The Michigan Care Improvement Registry (MCIR), a statewide immunization registry, was expanded in 2006 to include an indicator, based on Medicaid administrative claims, that prompts providers to offer influenza vaccine to high-risk children (ie, those with chronic conditions). To assess primary care providers' experiences with the MCIR high-risk indicator. A cross-sectional, self-administered survey mailed in July 2009. State of Michigan. A total of 300 family physicians and 300 pediatricians who served as primary care providers for children in Michigan's Medicaid program. Provider experiences with the high-risk indicator; suggestions for improvement. Response rate was 79%. Only 32% of pediatricians and 17% of family physicians recalled seeing the high-risk indicator during the 2008-2009 influenza season. Of those who saw the indicator, 48% rated it as "helpful" or "very helpful" in identifying which children should receive flu vaccine. To improve its usefulness, 77% of respondents wanted the indicator to reflect all children, rather than only those enrolled in Medicaid, and 71% wanted MCIR to generate a list of high-risk children in their practice. Three years after implementation, the registry-based high-risk indicator is not viewed by most providers. Half of those who saw the indicator found it helpful, and most respondents endorsed enhancements to broaden its scope. Future work should explore whether enhanced capabilities help to facilitate identification of priority cases by providers.

Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway

PubMed Central

Mohn, Kristin G.-I.; Cox, Rebecca Jane; Tunheim, Gro; Berdal, Jan Erik; Hauge, Anna Germundsson; Jul-Larsen, Åsne; Peters, Bjoern; Oftung, Fredrik

2015-01-01

Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza. PMID:26606759

Leptin and Leptin-Related Gene Polymorphisms, Obesity, and Influenza A/H1N1 Vaccine–Induced Immune Responses in Older Individuals

PubMed Central

Ovsyannikova, Inna G.; White, Sarah J.; Larrabee, Beth R.; Grill, Diane E.; Jacobson, Robert M.; Poland, Gregory A.

2014-01-01

Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (5074 years old) who were immunized with inactivated TIV influenza vacci–ne that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r=0.23, p=0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p = 0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine. PMID:24360890

Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

PubMed Central

Lefevre, Eric A.; Carr, B. Veronica; Inman, Charlotte F.; Prentice, Helen; Brown, Ian H.; Brookes, Sharon M.; Garcon, Fanny; Hill, Michelle L.; Iqbal, Munir; Elderfield, Ruth A.; Barclay, Wendy S.; Gubbins, Simon; Bailey, Mick; Charleston, Bryan

2012-01-01

Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4−CD8+ (cytotoxic) and CD4+CD8+ (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions. PMID:22427834

Fibroblast activation protein is dispensable in the anti-influenza immune response in mice

PubMed Central

Chowdhury, Sumaiya; Polak, Natasa

2017-01-01

Fibroblast activation protein alpha (FAP) is a unique dual peptidase of the S9B serine protease family, being capable of both dipeptidyl peptidase and endopeptidase activities. FAP is expressed at low level in healthy adult organs including the pancreas, cervix, uterus, submaxillary gland and the skin, and highly upregulated in embryogenesis, chronic inflammation and tissue remodelling. It is also expressed by cancer-associated stromal fibroblasts in more than 90% of epithelial tumours. FAP has enzymatic and non-enzymatic functions in the growth, immunosuppression, invasion and cell signalling of tumour cells. FAP deficient mice are fertile and viable with no gross abnormality, but little data exist on the role of FAP in the immune system. FAP is upregulated in association with microbial stimulation and chronic inflammation, but its function in infection remains unknown. We showed that major populations of immune cells including CD4+ and CD8+ T cells, B cells, dendritic cells and neutrophils are generated and maintained normally in FAP knockout mice. Upon intranasal challenge with influenza virus, FAP mRNA was increased in the lungs and lung-draining lymph nodes. Nonetheless, FAP deficient mice showed similar pathologic kinetics to wildtype controls, and were capable of supporting normal anti-influenza T and B cell responses. There was no evidence of compensatory upregulation of other DPP4 family members in influenza-infected FAP-deficient mice. FAP appears to be dispensable in anti-influenza adaptive immunity. PMID:28158223

The 2009 Influenza Pandemic: An Overview

DTIC Science & Technology

2009-10-15

to receive the pandemic vaccine nonetheless. 42 See, for example, the figure by Sanofi Pasteur (a flu vaccine manufacturer), “A(H1N1) Vaccine ...made by four companies: Sanofi Pasteur Inc., CSL Limited, Novartis Vaccines and Diagnostics Limited, and MedImmune LLC.46 The first three products...officials have procured millions of doses of pandemic flu vaccine , and have begun a voluntary nationwide vaccination program. It is being coordinated

Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults.

PubMed

Ikematsu, Hideyuki; Nagai, Hideaki; Kawashima, Masahiro; Kawakami, Yasunobu; Tenjinbaru, Kazuyoshi; Li, Ping; Walravens, Karl; Gillard, Paul; Roman, François

2012-02-01

Background Long-term persistence of immune response and safety of two doses of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) administered 21 d apart was evaluated in Japanese adults [NCT00989612]. Methods One-hundred healthy subjects aged 20-64 y (stratified [1:1] into two age strata 20-40 y and 41-64 y) received 21 d apart, two doses of AS03-adjuvanted 3.75µg haemagglutinin (HA) H1N1 2009 vaccine. Immunogenicity data by haemagglutination inhibition (HI) assay six months after the first vaccine dose (Day 182) and microneutralization assay following each of the two vaccine doses (Days 21 and 42) and at Day 182 are reported here. Results Persistence of strong HI immune response was observed at Day 182 that met the US and European regulatory thresholds for pandemic influenza vaccines (seroprotection rate: 95%; seroconversion rate: 93%; geometric mean fold-rise: 20). The neutralizing antibody response against the A/Netherlands/602/2009 strain (antigenically similar to vaccine-strain) persisted for at least up to Day 182 (vaccine response rate: 76%; geometric mean titer: 114.4) and paralleled the HI immune response at all time points. No marked difference was observed in HI antibody persistence and neutralising antibody response between the two age strata. The vaccine had a clinically-acceptable safety profile. Conclusion Two priming doses of H1N1 2009 pandemic influenza vaccine induced an immune response persisting for at least six months after the first vaccine dose. This could be beneficial in evaluating the importance and effect of vaccination with this AS03-adjuvanted pandemic influenza vaccine.

Bovine colostrum enhances natural killer cell activity and immune response in a mouse model of influenza infection and mediates intestinal immunity through toll-like receptors 2 and 4.

PubMed

Wong, Eric B; Mallet, Jean-François; Duarte, Jairo; Matar, Chantal; Ritz, Barry W

2014-04-01

Oral administration of bovine colostrum affects intestinal immunity, including an increased percentage of natural killer (NK) cells. However, effects on NK cell cytotoxic activity and resistance to infection as well as a potential mechanism remain unclear. Therefore, we investigated the effects of bovine colostrum (La Belle, Inc, Bellingham, WA) on the NK cytotoxic response to influenza infection and on toll-like receptor (TLR) activity in a primary intestinal epithelial cell culture. We hypothesized that colostrum would increase NK cell activity and that TLR-2 and TLR-4 blocking would reduce interleukin 6 production by epithelial cells in response to contact stimulation with colostrum. Four-month-old female C57BL/6 mice were supplemented with 1 g of colostrum per kilogram of body weight before and after infection with influenza A virus (H1N1). Animals were assessed for weight loss, splenic NK cell activity, and lung virus titers. Colostrum-supplemented mice demonstrated less reduction in body weight after influenza infection, indicating a less severe infection, increased NK cell cytotoxicity, and less virus burden in the lungs compared with controls. Colostrum supplementation enhanced NK cell cytotoxicity and improved the immune response to primary influenza virus infection in mice. To investigate a potential mechanism, a primary culture of small intestine epithelial cells was then stimulated with colostrum. Direct activation of epithelial cells resulted in increased interleukin 6 production, which was inhibited with TLR-2 and TLR-4 blocking antibodies. The interaction between colostrum and immunity may be dependent, in part, on the interaction of colostrum components with innate receptors at the intestinal epithelium, including TLR-2 and TLR-4. Copyright © 2014 Elsevier Inc. All rights reserved.

Pre-clinical evaluation of a replication-competent recombinant adenovirus serotype 4 vaccine expressing influenza H5 hemagglutinin.

PubMed

Alexander, Jeff; Ward, Simone; Mendy, Jason; Manayani, Darly J; Farness, Peggy; Avanzini, Jenny B; Guenther, Ben; Garduno, Fermin; Jow, Lily; Snarsky, Victoria; Ishioka, Glenn; Dong, Xin; Vang, Lo; Newman, Mark J; Mayall, Tim

2012-01-01

Influenza virus remains a significant health and social concern in part because of newly emerging strains, such as avian H5N1 virus. We have developed a prototype H5N1 vaccine using a recombinant, replication-competent Adenovirus serotype 4 (Ad4) vector, derived from the U.S. military Ad4 vaccine strain, to express the hemagglutinin (HA) gene from A/Vietnam/1194/2004 influenza virus (Ad4-H5-Vtn). Our hypothesis is that a mucosally-delivered replicating Ad4-H5-Vtn recombinant vector will be safe and induce protective immunity against H5N1 influenza virus infection and disease pathogenesis. The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3 region of Ad4 to accommodate the influenza HA gene. Replication and growth kinetics of the vaccine virus in multiple human cell lines indicated that the vaccine virus is attenuated relative to the wild type virus. Expression of the HA transgene in infected cells was documented by flow cytometry, western blot analysis and induction of HA-specific antibody and cellular immune responses in mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine were protected against lethal H5N1 reassortant viral challenge even in the presence of pre-existing immunity to the Ad4 wild type virus. Several non-clinical attributes of this vaccine including safety, induction of HA-specific humoral and cellular immunity, and efficacy were demonstrated using an animal model to support Phase 1 clinical trial evaluation of this new vaccine.

Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events.

PubMed

Läubli, Heinz; Balmelli, Catharina; Kaufmann, Lukas; Stanczak, Michal; Syedbasha, Mohammedyaseen; Vogt, Dominik; Hertig, Astrid; Müller, Beat; Gautschi, Oliver; Stenner, Frank; Zippelius, Alfred; Egli, Adrian; Rothschild, Sacha I

2018-05-22

Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined. We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade. We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2 months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population.

Positive Selection in CD8+ T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages.

PubMed

Machkovech, Heather M; Bedford, Trevor; Suchard, Marc A; Bloom, Jesse D

2015-11-01

Numerous experimental studies have demonstrated that CD8(+) T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8(+) T cells. Here we use a novel computational approach to test for selection in CD8(+) T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8(+) T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8(+) T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8(+) T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. There is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8(+) T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal models and are associated with decreased symptoms in humans, no studies have proven with statistical significance that influenza virus evolves under positive selection to escape T cells. Here we use comparisons of human and swine influenza viruses to rigorously demonstrate that human influenza virus evolves under pressure to fix mutations in the nucleoprotein that promote escape from T cells. We further show that viruses with these mutations have a selective advantage since they are preferentially located on the "trunk" of the phylogenetic tree. Overall, our results show that CD8(+) T cells targeting nucleoprotein play an important role in shaping influenza virus evolution. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Discrete Dynamical Modeling of Influenza Virus Infection Suggests Age-Dependent Differences in Immunity.

PubMed

Keef, Ericka; Zhang, Li Ang; Swigon, David; Urbano, Alisa; Ermentrout, G Bard; Matuszewski, Michael; Toapanta, Franklin R; Ross, Ted M; Parker, Robert S; Clermont, Gilles

2017-12-01

Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit a delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and a greater likelihood of death. Our study applies a rule-based model to infer which components of the immune response are most changed in an aged host. Two groups of BALB/c mice (aged 12 to 16 weeks and 72 to 76 weeks) were infected with 2 inocula: a survivable dose of 50 PFU and a lethal dose of 500 PFU. Data were measured at 10 points over 19 days in the sublethal case and at 6 points over 7 days in the lethal case, after which all mice had died. Data varied primarily in the onset of immunity, particularly the inflammatory response, which led to a 2-day delay in the clearance of the virus from older hosts in the sublethal cohort. We developed a Boolean model to describe the interactions between the virus and 21 immune components, including cells, chemokines, and cytokines, of innate and adaptive immunity. The model identifies distinct sets of rules for each age group by using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. Our model accurately simulates the immune responses of mice of both ages and with both inocula included in the data (95% accurate for younger mice and 94% accurate for older mice) and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus infection. IMPORTANCE Influenza virus infection causes high morbidity and mortality rates every year, especially in the elderly. The elderly tend to have a delayed onset of many immune responses as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the intrahost immune response to influenza virus infection. The model is fit to experimental data for young and old mice infected with influenza virus. We generated distinct sets of rules for each age group to capture the temporal differences seen in the immune responses of these mice. These rules describe a network of interactions leading to either clearance of the virus or death of the host, depending on the initial dosage of the virus. Our models clearly demonstrate differences in these two age groups, particularly in the innate immune responses. Copyright © 2017 American Society for Microbiology.

The Lung Immune Response to Nontypeable Haemophilus influenzae (Lung Immunity to NTHi)

PubMed Central

King, Paul T.; Sharma, Roleen

2015-01-01

Haemophilus influenzae is divided into typeable or nontypeable strains based on the presence or absence of a polysaccharide capsule. The typeable strains (such as type b) are an important cause of systemic infection, whilst the nontypeable strains (designated as NTHi) are predominantly respiratory mucosal pathogens. NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract. In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease. NTHi induces a strong inflammatory response in the respiratory tract with activation of immune responses, which often fail to clear the bacteria from the lung. This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology. This review will summarise the current literature about the lung immune response to nontypeable Haemophilus influenzae, a topic that has important implications for patient management. PMID:26114124

Local and systemic immune response in pigs during subclinical and clinical swine influenza infection.

PubMed

Pomorska-Mól, M; Kwit, K; Markowska-Daniel, I; Kowalski, C; Pejsak, Z

2014-10-01

Local and systemic immune responses in pigs intranasally (IN) and intratracheally (IT) inoculated with swine influenza virus (SIV) were studied. No clinical signs were observed in IN-inoculated pigs, while IT-inoculated pigs developed typical signs of influenza. Significantly higher titres of specific antibodies and changes of haematological parameters were found only in IT-inoculated pigs. Because positive correlations between viral titre, local cytokine concentration, and lung pathology have been observed, we hypothesise that both viral load and the local secretion of cytokines play a role in the induction of lung lesions. It could be that a higher replication of SIV stimulates immune cells to secrete higher amounts of cytokines. The results of the present study indicate that pathogenesis of SIV is dependent on both, the damage caused to the lung parenchyma directly by virus, and the effects on the cells of the host's immune system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig.

PubMed

Tungatt, Katie; Dolton, Garry; Morgan, Sophie B; Attaf, Meriem; Fuller, Anna; Whalley, Thomas; Hemmink, Johanneke D; Porter, Emily; Szomolay, Barbara; Montoya, Maria; Hammond, John A; Miles, John J; Cole, David K; Townsend, Alain; Bailey, Mick; Rizkallah, Pierre J; Charleston, Bryan; Tchilian, Elma; Sewell, Andrew K

2018-05-01

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens.

Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig

PubMed Central

Morgan, Sophie B.; Attaf, Meriem; Szomolay, Barbara; Miles, John J.; Townsend, Alain; Bailey, Mick; Charleston, Bryan; Tchilian, Elma

2018-01-01

There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens. PMID:29772011

Type 1 Responses of Human Vγ9Vδ2 T Cells to Influenza A Viruses▿

PubMed Central

Qin, Gang; Liu, Yinping; Zheng, Jian; Ng, Iris H. Y.; Xiang, Zheng; Lam, Kwok-Tai; Mao, Huawei; Li, Hong; Peiris, J. S. Malik; Lau, Yu-Lung; Tu, Wenwei

2011-01-01

γδ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells participated in anti-influenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs) in vitro. However, little is known about the noncytolytic responses and trafficking program of γδ T cells to influenza virus. In this study, we found that Vγ9Vδ2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-γ). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated γδ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-γ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in Vγ9Vδ2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of Vγ9Vδ2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human Vγ9Vδ2 T cells against influenza virus infection. PMID:21752902

The influence of pregnancy on systemic immunity.

PubMed

Pazos, Michael; Sperling, Rhoda S; Moran, Thomas M; Kraus, Thomas A

2012-12-01

Adaptations in maternal systemic immunity are presumed to be responsible for observed alterations in disease susceptibility and severity as pregnancy progresses. Epidemiological evidence as well as animal studies have shown that influenza infections are more severe during the second and third trimesters of pregnancy, resulting in greater morbidity and mortality, although the reason for this is still unclear. Our laboratory has taken advantage of 20 years of experience studying the murine immune response to respiratory viruses to address questions of altered immunity during pregnancy. With clinical studies and unique animal model systems, we are working to define the mechanisms responsible for altered immune responses to influenza infection during pregnancy and what roles hormones such as estrogen or progesterone play in these alterations.

Humoral and cell-mediated immune responses to influenza vaccination in equine metabolic syndrome (EMS) horses.

PubMed

Elzinga, Sarah; Reedy, Stephanie; Barker, Virginia D; Chambers, Thomas M; Adams, Amanda A

2018-05-01

Obesity is an increasing problem in the equine population with recent reports indicating that the percentage of overweight horses may range anywhere from 20.6-51%. Obesity in horses has been linked to more serious health concerns such as equine metabolic syndrome (EMS). EMS is a serious problem in the equine industry given its defining characteristics of insulin dysregualtion and obesity, as well as the involvement of laminitis. Little research however has been conducted to determine the effects of EMS on routine healthcare of these horses, in particular how they respond to vaccination. It has been shown that obese humans and mice have decreased immune responses to vaccination. EMS may have similar effects on vaccine responses in horses. If this is the case, these animals may be more susceptible to disease, acting as unknown disease reservoirs. Therefore, we investigated the effects of EMS on immune responses to routine influenza vaccination. Twenty-five adult horses of mixed-sex and mixed-breed (8-21 years old) horses; 13 EMS and 12 non-EMS were selected. Within each group, 4 horses served as non-vaccinate saline controls and the remaining horses were vaccinated with a commercially available equine influenza vaccine. Vaccination (influenza or saline) was administered on weeks 0 and 3, and peripheral blood samples taken on week 0 prior to vaccination and on weeks 1, 2, 3, 4, and 5 post vaccination. Blood samples were used to measure hemagglutination inhibition (HI) titers and equine influenza specific IgGa, IgGb, and IgGT levels. Blood samples were also used to isolate peripheral blood mononuclear cells (PBMCs) for analysis of cell mediated immune (CMI) responses via real-time polymerase chain reaction (RT-PCR). All horses receiving influenza vaccination responded with significant increases (P < 0.05) in HI titers, and IgGa and IgGb equine influenza specific antibodies following vaccination compared to saline controls. EMS did not significantly affect (P > 0.05) humoral immune responses as measured by HI titers or IgG antibody isotypes to influenza vaccination. There was an effect of metabolic status on CMI responses, with influenza vaccinated EMS horses having lower gene expression of IFN-γ (P = 0.02) and IL-2 (P = 0.01) compared to vaccinated non-EMS control horses. Given these results, it appears that while metabolic status does not influence humoral responses to an inactivated influenza vaccine in horses, horses with EMS appear to have a reduced CMI response to vaccination compared to metabolically normal, non-EMS control horses. Copyright © 2018 Elsevier B.V. All rights reserved.

Modified vaccinia virus Ankara encoding influenza virus hemagglutinin induces heterosubtypic immunity in macaques.

PubMed

Florek, Nicholas W; Weinfurter, Jason T; Jegaskanda, Sinthujan; Brewoo, Joseph N; Powell, Tim D; Young, Ginger R; Das, Subash C; Hatta, Masato; Broman, Karl W; Hungnes, Olav; Dudman, Susanne G; Kawaoka, Yoshihiro; Kent, Stephen J; Stinchcomb, Dan T; Osorio, Jorge E; Friedrich, Thomas C

2014-11-01

Current influenza virus vaccines primarily aim to induce neutralizing antibodies (NAbs). Modified vaccinia virus Ankara (MVA) is a safe and well-characterized vector for inducing both antibody and cellular immunity. We evaluated the immunogenicity and protective efficacy of MVA encoding influenza virus hemagglutinin (HA) and/or nucleoprotein (NP) in cynomolgus macaques. Animals were given 2 doses of MVA-based vaccines 4 weeks apart and were challenged with a 2009 pandemic H1N1 isolate (H1N1pdm) 8 weeks after the last vaccination. MVA-based vaccines encoding HA induced potent serum antibody responses against homologous H1 or H5 HAs but did not stimulate strong T cell responses prior to challenge. However, animals that received MVA encoding influenza virus HA and/or NP had high frequencies of virus-specific CD4(+) and CD8(+) T cell responses within the first 7 days of H1N1pdm infection, while animals vaccinated with MVA encoding irrelevant antigens did not. We detected little or no H1N1pdm replication in animals that received vaccines encoding H1 (homologous) HA, while a vaccine encoding NP from an H5N1 isolate afforded no protection. Surprisingly, H1N1pdm viral shedding was reduced in animals vaccinated with MVA encoding HA and NP from an H5N1 isolate. This reduced shedding was associated with cross-reactive antibodies capable of mediating antibody-dependent cellular cytotoxicity (ADCC) effector functions. Our results suggest that ADCC plays a role in cross-protective immunity against influenza. Vaccines optimized to stimulate cross-reactive antibodies with ADCC function may provide an important measure of protection against emerging influenza viruses when NAbs are ineffective. Current influenza vaccines are designed to elicit neutralizing antibodies (NAbs). Vaccine-induced NAbs typically are effective but highly specific for particular virus strains. Consequently, current vaccines are poorly suited for preventing the spread of newly emerging pandemic viruses. Therefore, we evaluated a vaccine strategy designed to induce both antibody and T cell responses, which may provide more broadly cross-protective immunity against influenza. Here, we show in a translational primate model that vaccination with a modified vaccinia virus Ankara encoding hemagglutinin from a heterosubtypic H5N1 virus was associated with reduced shedding of a pandemic H1N1 virus challenge, while vaccination with MVA encoding nucleoprotein, an internal viral protein, was not. Unexpectedly, this reduced shedding was associated with nonneutralizing antibodies that bound H1 hemagglutinin and activated natural killer cells. Therefore, antibody-dependent cellular cytotoxicity (ADCC) may play a role in cross-protective immunity to influenza virus. Vaccines that stimulate ADCC antibodies may enhance protection against pandemic influenza virus. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Modified Vaccinia Virus Ankara Encoding Influenza Virus Hemagglutinin Induces Heterosubtypic Immunity in Macaques

PubMed Central

Florek, Nicholas W.; Weinfurter, Jason T.; Jegaskanda, Sinthujan; Brewoo, Joseph N.; Powell, Tim D.; Young, Ginger R.; Das, Subash C.; Hatta, Masato; Broman, Karl W.; Hungnes, Olav; Dudman, Susanne G.; Kawaoka, Yoshihiro; Kent, Stephen J.; Stinchcomb, Dan T.

2014-01-01

ABSTRACT Current influenza virus vaccines primarily aim to induce neutralizing antibodies (NAbs). Modified vaccinia virus Ankara (MVA) is a safe and well-characterized vector for inducing both antibody and cellular immunity. We evaluated the immunogenicity and protective efficacy of MVA encoding influenza virus hemagglutinin (HA) and/or nucleoprotein (NP) in cynomolgus macaques. Animals were given 2 doses of MVA-based vaccines 4 weeks apart and were challenged with a 2009 pandemic H1N1 isolate (H1N1pdm) 8 weeks after the last vaccination. MVA-based vaccines encoding HA induced potent serum antibody responses against homologous H1 or H5 HAs but did not stimulate strong T cell responses prior to challenge. However, animals that received MVA encoding influenza virus HA and/or NP had high frequencies of virus-specific CD4+ and CD8+ T cell responses within the first 7 days of H1N1pdm infection, while animals vaccinated with MVA encoding irrelevant antigens did not. We detected little or no H1N1pdm replication in animals that received vaccines encoding H1 (homologous) HA, while a vaccine encoding NP from an H5N1 isolate afforded no protection. Surprisingly, H1N1pdm viral shedding was reduced in animals vaccinated with MVA encoding HA and NP from an H5N1 isolate. This reduced shedding was associated with cross-reactive antibodies capable of mediating antibody-dependent cellular cytotoxicity (ADCC) effector functions. Our results suggest that ADCC plays a role in cross-protective immunity against influenza. Vaccines optimized to stimulate cross-reactive antibodies with ADCC function may provide an important measure of protection against emerging influenza viruses when NAbs are ineffective. IMPORTANCE Current influenza vaccines are designed to elicit neutralizing antibodies (NAbs). Vaccine-induced NAbs typically are effective but highly specific for particular virus strains. Consequently, current vaccines are poorly suited for preventing the spread of newly emerging pandemic viruses. Therefore, we evaluated a vaccine strategy designed to induce both antibody and T cell responses, which may provide more broadly cross-protective immunity against influenza. Here, we show in a translational primate model that vaccination with a modified vaccinia virus Ankara encoding hemagglutinin from a heterosubtypic H5N1 virus was associated with reduced shedding of a pandemic H1N1 virus challenge, while vaccination with MVA encoding nucleoprotein, an internal viral protein, was not. Unexpectedly, this reduced shedding was associated with nonneutralizing antibodies that bound H1 hemagglutinin and activated natural killer cells. Therefore, antibody-dependent cellular cytotoxicity (ADCC) may play a role in cross-protective immunity to influenza virus. Vaccines that stimulate ADCC antibodies may enhance protection against pandemic influenza virus. PMID:25210172

Estimating transmission of avian influenza in wild birds from incomplete epizootic data: implications for surveillance and disease spreac

USGS Publications Warehouse

Henaux, Viviane; Jane Parmley,; Catherine Soos,; Samuel, Michael D.

2013-01-01

Synthesis and applications. Our study highlights the potential of integrating incomplete surveillance data with epizootic models to quantify disease transmission and immunity. This modelling approach provides an important tool to understand spatial and temporal epizootic dynamics and inform disease surveillance. Our findings suggest focusing highly pathogenic avian influenza virus (HPAIv) surveillance on postbreeding areas where mortality of immunologically naïve hatch-year birds is most likely to occur, and collecting serology to enhance HPAIv detection. Our modelling approach can integrate various types of disease data facilitating its use with data from other surveillance programs (as illustrated by the estimation of infection rate during an HPAIv outbreak in mute swansCygnus olor in Europe).

Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults.

PubMed

Herati, Ramin Sedaghat; Reuter, Morgan A; Dolfi, Douglas V; Mansfield, Kathleen D; Aung, Htin; Badwan, Osama Z; Kurupati, Raj K; Kannan, Senthil; Ertl, Hildegund; Schmader, Kenneth E; Betts, Michael R; Canaday, David H; Wherry, E John

2014-10-01

Although influenza vaccination is recommended for all adults annually, the incidence of vaccine failure, defined as weak or absent increase in neutralizing Ab titers, is increased in the elderly compared with young adults. The T follicular helper cell (Tfh) subset of CD4 T cells provides B cell help in germinal centers and is necessary for class-switched Ab responses. Previous studies suggested a role for circulating Tfh cells (cTfh) following influenza vaccination in adults, but cTfh have not been studied in elderly adults in whom weak vaccine responses are often observed. In this study, we studied cTfh expressing CXCR5 and programmed death-1 (PD-1). cTfh from elderly adults were present at reduced frequency, had decreased in vitro B cell help ability, and had greater expression of ICOS compared with young adults. At 7 d after inactivated influenza vaccination, cTfh correlated with influenza vaccine-specific IgM and IgG responses in young adults but not in elderly adults. In sum, we have identified aging-related changes in cTfh that correlated with reduced influenza vaccine responses. Future rational vaccine design efforts should incorporate Tfh measurement as an immune correlate of protection, particularly in the setting of aging. Copyright © 2014 by The American Association of Immunologists, Inc.

Positive regulation of humoral and innate immune responses induced by inactivated Avian Influenza Virus vaccine in broiler chickens.

PubMed

Abdallah, Fatma; Hassanin, Ola

2015-12-01

Avian Influenza (AI) vaccines are widely used for mammals and birds in a trial to eliminate the Avian Influenza virus (AIV) infection from the world. However and up till now the virus is still existed via modulation of its antigenic structure to evade the pressure of host immune responses. For a complete understanding of the immune responses following AI vaccination in chickens, the modulations of the chickens humoral immune responses and interferon-alpha signaling pathway, as a fundamental part of the innate immune responses, were investigated. In our study, we measured the humoral immune response using hemagglutination-inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) tests. In addition, chicken interferon-alpha pathway components was measured at RNA levels using Quantitative Real-time PCR (qRT-PCR) following one dose of inactivated H5N1 influenza vaccine at 14 days of age. In this study, the protective levels of humoral antibody responses were observed at 14, 21 and 28 days following immunization with inactivated (Re-1/H5N1) AI vaccine. In the chicken spleen cells, up regulation in the chicken interferon-alpha pathway components (MX1 & IRF7) was existed as early as 48 h post vaccination and remained until 28 days post vaccination at the endogenous state. However, after the recall with ex-vivo stimulation, the up regulation was more pronounced in the transcriptional factor (IRF7) compared to the antiviral gene (MX1) at 28 days post vaccination. So far, from our results it appears that the inactivated H5N1 vaccine can trigger the chicken interferon-alpha signaling pathway as well as it can elicit protective humoral antibody responses.

Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus: studies in the pig model of influenza.

PubMed

Qiu, Yu; De Hert, Karl; Van Reeth, Kristien

2015-09-24

Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs.

Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawano, Masaaki; Morikawa, Katsuma; Suda, Tatsuya

Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A{sup ⁎}02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A{sup ⁎}02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimericmore » SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties.« less

A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

PubMed Central

Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

2016-01-01

A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens

PubMed Central

Jang, Hyesun; Elaish, Mohamed; KC, Mahesh; Abundo, Michael C.; Ghorbani, Amir; Lee, Chang-Won

2018-01-01

Outbreaks of novel highly pathogenic avian influenza viruses have been reported in poultry species in the United States since 2014. These outbreaks have proven the limitations of biosecurity control programs, and new tools are needed to reinforce the current avian influenza control arsenal. Some enzootic countries have implemented inactivated influenza vaccine (IIV) in their control programs, but there are serious concerns that a long-term use of IIV without eradication may result in the selection of novel antigenically divergent strains. A broadly protective vaccine is needed, such as live-attenuated influenza vaccine (LAIV). We showed in our previous studies that pc4-LAIV (a variant that encodes a C-terminally truncated NS1 protein) can provide significant protection against heterologous challenge virus in chickens vaccinated at 2–4 weeks of age through upregulation of innate and adaptive immune responses. The current study was conducted to compare the performances of pc4-LAIV and IIV in young chickens vaccinated at 1 day of age. A single dose of pc4-LAIV was able to induce stronger innate and mucosal IgA responses and protect young immunologically immature chickens better than a single dose of IIV. Most importantly, when 1-day-old chickens were intranasally primed with pc4-LAIV and subcutaneously boosted with IIV three weeks later, they showed a rapid, robust, and highly cross-reactive serum antibody response and a high level of mucosal IgA antibody response. This vaccination regimen warrants further optimization to increase its range of protection. PMID:29624615

Immunogenicity and clinical protection against equine influenza by gene-based DNA vaccination of ponies

PubMed Central

Ault, Alida; Zajac, Alyse M.; Kong, Wing-Pui; Gorres, J. Patrick; Royals, Michael; Wei, Chih-Jen; Bao, Saran; Yang, Zhi-yong; Reedy, Stephanie E.; Sturgill, Tracy L.; Page, Allen E.; Donofrio-Newman, Jennifer; Adams, Amanda A.; Balasuriya, Udeni B.R.; Horohov, David W.; Chambers, Thomas M.; Nabel, Gary J.; Rao, Srinivas S.

2012-01-01

Equine influenza A (H3N8) virus is a leading cause of infectious respiratory disease in horses causing widespread morbidity and economic losses. As with influenza in other species, equine influenza strains continuously mutate, requiring constant re-evaluation of current vaccines and development of new vaccines. Current inactivated (killed) vaccines, while efficacious, only offer limited protection against multiple strains and require frequent boosts. Ongoing research into new vaccine technologies, including gene-based vaccines, aims to increase the neutralization potency, breadth, and duration of protective immunity of new or existing vaccines. In these hypothesis-generating experiments, we demonstrate that a DNA vaccine expressing the hemagglutinin protein of equine H3N8 influenza virus generates homologous and heterologous immune responses, and protects against clinical disease and viral replication following homologous H3N8 infection in horses. Furthermore, we demonstrate that a needle-free delivery device is as efficient and effective as conventional parenteral injection using a needle and syringe. The observed trends in this study drive the hypothesis that DNA vaccines offer a safe, effective, and promising alternative approach for veterinary vaccines against influenza, and applicable to combat equine influenza. PMID:22449425

Influenza vaccination of Michigan children by provider type, 2010-2011.

PubMed

Clayton, Joshua L; Potter, Rachel C; Wells, Eden V; Carlton, Cristi A; Boulton, Matthew L

2014-07-01

Influenza vaccination for all children aged 6 months to 18 years has been recommended since 2008 to prevent flu-related morbidity and mortality. However, 2010-2011 influenza vaccine coverage estimates show under-vaccination in children of all ages. We examined predictors of influenza vaccination in Michigan during the 2010-2011 influenza season. To determine whether immunization provider type was associated with a child's influenza vaccination in Michigan and assess whether county-level factors were confounders of the association. Influenza vaccinations reported to the Michigan Care Improvement Registry from the 2010-2011 influenza season were analyzed in 2012 to estimate ORs for the association between immunization provider type and influenza vaccination. Among 2,373,826 Michigan children aged 6 months through 17 years, 17% were vaccinated against influenza and lower vaccination rates were observed for public compared to private providers (13% vs 18%). In the unadjusted model, public providers had lower odds of vaccinating children compared to private providers (OR=0.60, 95% CI=0.60, 0.61). County-level factors, including percentage of families living below the poverty line, median household income, and percentage black race, were not shown to confound the association. In the adjusted models, public providers had lower odds of vaccinating children compared to private providers (OR=0.87, 95% CI=0.86, 0.88). Although a child's likelihood of influenza vaccination in Michigan varies by provider type, more effective strategies to improve influenza vaccination rates for all Michigan children are needed. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.

PubMed

Koutsakos, Marios; Wheatley, Adam K; Loh, Liyen; Clemens, E Bridie; Sant, Sneha; Nüssing, Simone; Fox, Annette; Chung, Amy W; Laurie, Karen L; Hurt, Aeron C; Rockman, Steve; Lappas, Martha; Loudovaris, Thomas; Mannering, Stuart I; Westall, Glen P; Elliot, Michael; Tangye, Stuart G; Wakim, Linda M; Kent, Stephen J; Nguyen, Thi H O; Kedzierska, Katherine

2018-02-14

Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T FH ) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5 - CXCR3 + antibody-secreting B cell population, CD21 hi CD27 + memory B cells, and CD21 lo CD27 + B cells. Activation of circulating T FH cells correlated with the development of both CD21 lo and CD21 hi memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8 + , mucosal-associated invariant T, γδ T, and natural killer cell activation. In addition, vaccine-induced B cells were not maintained in peripheral blood at 1 year after vaccination. We provide a dissection of rHA-specific B cells across seven human tissue compartments, showing that influenza-specific memory (CD21 hi CD27 + ) B cells primarily reside within secondary lymphoid tissues and the lungs. Our study suggests that a rational design of universal vaccines needs to consider circulating T FH cells, preexisting serological memory, and tissue compartmentalization for effective B cell immunity, as well as to improve targeting cellular T cell immunity. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Long-term persistence of humoral and cellular immune responses induced by an AS03A-adjuvanted H1N1 2009 influenza vaccine: an open-label, randomized study in adults aged 18-60 years and older.

PubMed

Van Damme, Pierre; Kafeja, Froukje; Bambure, Vinod; Hanon, Emmanuel; Moris, Philippe; Roman, François; Gillard, Paul

2013-07-01

This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009 strain, six and 12 mo after adults received one dose (n = 138) or two doses (n = 102; 21 d apart) of a 3.75 µg Hemagglutinin antigen AS03-adjuvanted H1N1 2009 vaccine (NCT00968526). Two hundred forty subjects (18-60 y: 120;>60 y: 120) were vaccinated. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. Exploratory analyses assessed the cell-mediated immune response (CMI) up to Month 12 and the influence of previous influenza vaccination on persistence of immune response. At Month 6, the CHMP criteria were met in subjects aged 18-60 y who received one or two vaccine doses and in subjects aged>60 y who received two vaccine doses. At Month 12, the CHMP criteria were met only in subjects aged 18-60 y who received two vaccine doses. Persistence of HI immune response against the vaccine strain was higher in subjects without prior influenza vaccination. Exploratory analyses showed that two doses of the H1N1 2009 vaccine induced persistence of H1N1-specific CD4+ T cells up to Month 6 and memory B cells up to Month 12. In conclusion, HI immune responses persisted up to 12 mo after vaccination with one-dose and two-dose regimens of the AS03-adjuvanted 3.75 µg HA H1N1 2009 pandemic influenza vaccine, although not all three CHMP guidance criteria for both groups were met at Month 6 and Month 12. The CD4+ T cell and B cell responses also persisted up to Month 12.

Extensive T cell cross-reactivity between diverse seasonal influenza strains in the ferret model.

PubMed

Reber, Adrian J; Music, Nedzad; Kim, Jin Hyang; Gansebom, Shane; Chen, Jufu; York, Ian

2018-04-17

Influenza virus causes widespread, yearly epidemics by accumulating surface protein mutations to escape neutralizing antibodies established from prior exposure. In contrast to antibody epitopes, T cell mediated immunity targets influenza epitopes that are more highly conserved and have potential for cross-protection. The extent of T cell cross-reactivity between a diverse array of contemporary and historical influenza strains was investigated in ferrets challenged with 2009 pandemic H1N1 influenza or the seasonal H3N2 strain, A/Perth/16/2009. Post-challenge cell-mediated immune responses demonstrated extensive cross-reactivity with a wide variety of contemporary and historical influenza A strains as well as influenza B. Responses in peripheral blood were undetectable by 36d post-challenge, but cross-reactivity persisted in spleen. The strongest responses targeted peptides from the NP protein and demonstrated cross-reactivity in both the CD4+ and CD8+ T cell populations. Cross-reactive CD4+ T cells also targeted HA and NA epitopes, while cross-reactive CD8+ T cells targeted internal M1, NS2, and PA. T cell epitopes demonstrated extensive cross-reactivity between diverse influenza strains in outbred animals, with NP implicated as a significant antigenic target demonstrating extensive cross-reactivity for both CD4+ and CD8+ T cells.

Antibody repertoire development in fetal and neonatal piglets. XVI. Influenza stimulates adaptive immunity, class switch and diversification of the IgG repertoire encoded by downstream C-gamma genes

USDA-ARS?s Scientific Manuscript database

Infection of germfree isolator piglets with swine influenza (S-FLU) that generates ds-RNA during replication causes elevation of Igs in serum and bronchial alveolar lavage (BAL), a very weak response to TNP conjugates but an immune response to S-FLU. The increased Igs levels result mainly from the p...

The influence of dual infection with herpes and influenza viruses on the differential blood cell count of mice.

PubMed

Ančicová, L; Dugovičová, V; Briestenská, K; Kostolanský, F; Varečková, E; Mistríková, J

Based on our previous results, which confirmed the role of latent gammaherpesvirus infection in alteration of immune homeostasis, we studied the influence of simultaneous infection with gammaherpes and influenza viruses on selected parameters of innate immunity, particularly on the subpopulations of peripheral blood cell leukocytes. The aim was to analyze changes of differential blood cell count of BALB/c mice persistently infected with murine gammaherpesvirus 68 (MHV-68) and subsequently co-infected with influenza A virus (IAV), in comparison to mice infected with MHV-68 or with IAV only. Our results showed that ongoing gammaherpesvirus latency in mice caused a decreased number of leukocytes after acute infection with IAV in comparison to a single acute IAV infection. However, increased proportion of neutrophils was measured in peripheral blood of IAV- infected and co-infected mice. Dual infection had no effect on the proportion of monocytes or basophilic and eosinophilic granulocytes. The number of atypical lymphocytes, usually accompanying the persistent infection with MHV-68, decreased in co-infected mice as a consequence of the acute infection with IAV. Persistent infection with gammaherpesvirus may thus modulate the host immune response to influenza A virus and the acute IAV infection can influence the immune homeostasis established by latent MHV-68 infection.

The role of social contacts and original antigenic sin in shaping the age pattern of immunity to seasonal influenza.

PubMed

Kucharski, Adam J; Gog, Julia R

2012-01-01

Recent serological studies of seasonal influenza A in humans suggest a striking characteristic profile of immunity against age, which holds across different countries and against different subtypes of influenza. For both H1N1 and H3N2, the proportion of the population seropositive to recently circulated strains peaks in school-age children, reaches a minimum between ages 35-65, then rises again in the older ages. This pattern is little understood. Variable mixing between different age classes can have a profound effect on disease dynamics, and is hence the obvious candidate explanation for the profile, but using a mathematical model of multiple influenza strains, we see that age dependent transmission based on mixing data from social contact surveys cannot on its own explain the observed pattern. Instead, the number of seropositive individuals in a population may be a consequence of 'original antigenic sin'; if the first infection of a lifetime dominates subsequent immune responses, we demonstrate that it is possible to reproduce the observed relationship between age and seroprevalence. We propose a candidate mechanism for this relationship, by which original antigenic sin, along with antigenic drift and vaccination, results in the age profile of immunity seen in empirical studies.

Highly pathogenic avian influenza virus infection of mallards with homo- and heterosubtypic immunity induced by low pathogenic avian influenza viruses.

PubMed

Fereidouni, Sasan R; Starick, Elke; Beer, Martin; Wilking, Hendrik; Kalthoff, Donata; Grund, Christian; Häuslaigner, Rafaela; Breithaupt, Angele; Lange, Elke; Harder, Timm C

2009-08-20

The potential role of wild birds as carriers of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 is still a matter of debate. Consecutive or simultaneous infections with different subtypes of influenza viruses of low pathogenicity (LPAIV) are very common in wild duck populations. To better understand the epidemiology and pathogenesis of HPAIV H5N1 infections in natural ecosystems, we investigated the influence of prior infection of mallards with homo- (H5N2) and heterosubtypic (H4N6) LPAIV on exposure to HPAIV H5N1. In mallards with homosubtypic immunity induced by LPAIV infection, clinical disease was absent and shedding of HPAIV from respiratory and intestinal tracts was grossly reduced compared to the heterosubtypic and control groups (mean GEC/100 microl at 3 dpi: 3.0 x 10(2) vs. 2.3 x 10(4) vs. 8.7 x 10(4); p<0.05). Heterosubtypic immunity induced by an H4N6 infection mediated a similar but less pronounced effect. We conclude that the epidemiology of HPAIV H5N1 in mallards and probably other aquatic wild bird species is massively influenced by interfering immunity induced by prior homo- and heterosubtypic LPAIV infections.

Psychosocial Correlates of Intention to Receive an Influenza Vaccination among Rural Adolescents

ERIC Educational Resources Information Center

Painter, Julia E.; Sales, Jessica M.; Pazol, Karen; Wingood, Gina M.; Windle, Michael; Orenstein, Walter A.; Diclemente, Ralph J.

2010-01-01

The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recently expanded annual influenza vaccination recommendations to include all children 6 months through 18 years of age. Adolescent attitudes toward influenza vaccination may play a key role in reaching this newly added age group. This study examined the…

Transcription factor regulation and cytokine expression following in vitro infection of primary chicken cell culture with low pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

Avian influenza virus (AIV) induced proinflammatory cytokine expression is believed to contribute to the disease pathogenesis following infection. However, there is limited information on the avian immune response to infection with low pathogenic avian influenza virus (LPAIV). To gain a better under...

Current evidence on intradermal influenza vaccines administered by Soluvia™ licensed micro injection system

PubMed Central

Icardi, Giancarlo; Orsi, Andrea; Ceravolo, Antonella; Ansaldi, Filippo

2012-01-01

Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability.   Data from clinical trials performed in children, adults <60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination. PMID:22293531

Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge

PubMed Central

Baz, Mariana; Boonnak, Kobporn; Paskel, Myeisha; Santos, Celia; Powell, Timothy; Townsend, Alain

2015-01-01

ABSTRACT New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppression of the hemagglutinin signal sequence, with the corresponding H1N1 and H5N1 cold-adapted (ca) live attenuated influenza virus vaccines in mice and ferrets. Administration of two doses of H1 or H5 S-FLU vaccines protected mice and ferrets from lethal challenge with homologous, heterologous, and heterosubtypic influenza viruses, and two doses of S-FLU and ca vaccines yielded comparable effects. Importantly, when ferrets immunized with one dose of H1 S-FLU or ca vaccine were challenged with the homologous H1N1 virus, the challenge virus failed to transmit to naive ferrets by the airborne route. S-FLU technology can be rapidly applied to any emerging influenza virus, and the promising preclinical data support further evaluation in humans. PMID:26489862

DAMPs and influenza virus infection in ageing.

PubMed

Samy, Ramar Perumal; Lim, Lina H K

2015-11-01

Influenza A virus (IAV) is a serious global health problem worldwide due to frequent and severe outbreaks. IAV causes significant morbidity and mortality in the elderly population, due to the ineffectiveness of the vaccine and the alteration of T cell immunity with ageing. The cellular and molecular link between ageing and virus infection is unclear and it is possible that damage associated molecular patterns (DAMPs) may play a role in the raised severity and susceptibility of virus infections in the elderly. DAMPs which are released from damaged cells following activation, injury or cell death can activate the immune response through the stimulation of the inflammasome through several types of receptors found on the plasma membrane, inside endosomes after endocytosis as well as in the cytosol. In this review, the detriment in the immune system during ageing and the links between influenza virus infection and ageing will be discussed. In addition, the role of DAMPs such as HMGB1 and S100/Annexin in ageing, and the enhanced morbidity and mortality to severe influenza infection in ageing will be highlighted. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced Mucosal Antibody Production and Protection against Respiratory Infections Following an Orally Administered Bacterial Extract

PubMed Central

Pasquali, Christian; Salami, Olawale; Taneja, Manisha; Gollwitzer, Eva S.; Trompette, Aurelien; Pattaroni, Céline; Yadava, Koshika; Bauer, Jacques; Marsland, Benjamin J.

2014-01-01

Secondary bacterial infections following influenza infection are a pressing problem facing respiratory medicine. Although antibiotic treatment has been highly successful over recent decades, fatalities due to secondary bacterial infections remain one of the leading causes of death associated with influenza. We have assessed whether administration of a bacterial extract alone is sufficient to potentiate immune responses and protect against primary infection with influenza, and secondary infections with either Streptococcus pneumoniae or Klebsiella pneumoniae in mice. We show that oral administration with the bacterial extract, OM-85, leads to a maturation of dendritic cells and B-cells characterized by increases in MHC II, CD86, and CD40, and a reduction in ICOSL. Improved immune responsiveness against influenza virus reduced the threshold of susceptibility to secondary bacterial infections, and thus protected the mice. The protection was associated with enhanced polyclonal B-cell activation and release of antibodies that were effective at neutralizing the virus. Taken together, these data show that oral administration of bacterial extracts provides sufficient mucosal immune stimulation to protect mice against a respiratory tract viral infection and associated sequelae. PMID:25593914

Discordant correlation between serological assays observed when measuring heterosubtypic responses against avian influenza H5 and H7 viruses in unexposed individuals.

PubMed

Molesti, Eleonora; Ferrara, Francesca; Lapini, Giulia; Montomoli, Emanuele; Temperton, Nigel

2014-01-01

The human population is constantly exposed to multiple influenza A subtypes due to zoonotic spillover and rapid viral evolution driven by intrinsic error-prone replication and immunological pressure. In this context, antibody responses directed against the HA protein are of importance since they have been shown to correlate with protective immunity. Serological techniques, detecting these responses, play a critical role for influenza surveillance, vaccine development, and assessment. As the recent human pandemics and avian influenza outbreaks have demonstrated, there is an urgent need to be better prepared to assess the contribution of the antibody response to protection against newly emerged viruses and to evaluate the extent of preexisting heterosubtypic immunity in populations. In this study, 68 serum samples collected from the Italian population between 1992 and 2007 were found to be positive for antibodies against H5N1 as determined by single radial hemolysis (SRH), but most were negative when evaluated using haemagglutination inhibition (HI) and microneutralisation (MN) assays. As a result of these discordant serological findings, the increased sensitivity of lentiviral pseudotypes was exploited in pseudotype-based neutralisation (pp-NT) assays and the results obtained provide further insight into the complex nature of humoral immunity against influenza A viruses.

Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch.

PubMed

Hirobe, Sachiko; Azukizawa, Hiroaki; Hanafusa, Takaaki; Matsuo, Kazuhiko; Quan, Ying-Shu; Kamiyama, Fumio; Katayama, Ichiro; Okada, Naoki; Nakagawa, Shinsaku

2015-07-01

Transcutaneous immunization (TCI) is an attractive vaccination method compared with conventional injectable vaccines because it is easier to administer without pain. We developed a dissolving microneedle patch (MicroHyala, MH) made of hyaluronic acid and showed that transcutaneous vaccination using MH induced a strong immune response against various antigens in mice. In the present study, we investigated the clinical safety and efficacy of a novel transcutaneous influenza vaccine using MH (flu-MH), which contains trivalent influenza hemagglutinins (15 μg each). Subjects of the TCI group were treated transcutaneously with flu-MH, and were compared with subjects who received subcutaneous injections of a solution containing 15 μg of each influenza antigen (SCI group). No severe local or systemic adverse events were detected in either group and immune responses against A/H1N1 and A/H3N2 strains were induced equally in the TCI and SCI groups. Moreover, the efficacy of the vaccine against the B strain in the TCI group was stronger than that in the SCI group. Influenza vaccination using MH is promising for practical use as an easy and effective method to replace conventional injections systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Does influenza vaccination improve pregnancy outcome? Methodological issues and research needs.

PubMed

Savitz, David A; Fell, Deshayne B; Ortiz, Justin R; Bhat, Niranjan

2015-11-25

Evidence that influenza vaccination during pregnancy is safe and effective at preventing influenza disease in women and their children through the first months of life is increasing. Several reports of reduced risk of adverse outcomes associated with influenza vaccination have generated interest in its potential for improving pregnancy outcome. Gavi, the Vaccine Alliance, estimates maternal influenza immunization programs in low-income countries would have a relatively modest impact on mortality compared to other new or under-utilized vaccines, however the impact would be substantially greater if reported vaccine effects on improved pregnancy outcomes were accurate. Here, we examine the available evidence and methodological issues bearing on the relationship between influenza vaccination and pregnancy outcome, particularly preterm birth and fetal growth restriction, and summarize research needs. Evidence for absence of harm associated with vaccination at a point in time is not symmetric with evidence of benefit, given the scenario in which vaccination reduces risk of influenza disease and, in turn, risk of adverse pregnancy outcome. The empirical evidence for vaccination preventing influenza in pregnant women is strong, but the evidence that influenza itself causes adverse pregnancy outcomes is inconsistent and limited in quality. Studies of vaccination and pregnancy outcome have produced mixed evidence of potential benefit but are limited in terms of influenza disease assessment and control of confounding, and their analytic methods often fail to fully address the longitudinal nature of pregnancy and influenza prevalence. We recommend making full use of results of randomized trials, re-analysis of existing observational studies to account for confounding and time-related factors, and quantitative assessment of the potential benefits of vaccination in improving pregnancy outcome, all of which should be informed by the collective engagement of experts in influenza, vaccines, and perinatal health. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Influenza-associated severe acute respiratory infections in 2 sentinel sites in Lebanon-September 2015 to August 2016.

PubMed

Saleh, Majd; Bazzi, Lara; Ismail, Ebstissam; Mroueh, Lina; Jammal, Nisrine; Elkholy, Amgad; Mrad, Pamela; Samadi, Ahmad Al; Hijazi, Ahmad; Abiad, Firass; Nsouli, Ghazi; Rady, Alissar; Khan, Wasiq; Malik, Mamunur; Zalloua, Pierre; Ammar, Walid; Ghosn, Nada

2018-05-01

Given the sparse information on the burden of influenza in Lebanon, the Ministry of Public Health established a sentinel surveillance for severe acute respiratory infections (SARI) to identify the attribution of influenza to reported cases. We aim to highlight the proportion of influenza-associated SARI from September 1st, 2015 to August 31st, 2016 in 2 Lebanese hospitals. The study was conducted in 2 sentinel sites located in Beirut suburbs and southern province of Lebanon. WHO's 2011 standardized SARI case definition was used. Data from September 1, 2015 to August 31, 2016 were reviewed, and all-cause hospital admission numbers were obtained. Nasopharyngeal swabs were collected and tested by RT-PCR. Descriptive and bivariate analyses were conducted using STATA 13. The 2 sentinel sites reported 746 SARI cases during the studied time frame: 467 from the southern province site and 279 from the Beirut suburbs site. SARI reports peaked between January and March 2016. All, except 4, cases were sampled, and a co-dominance of influenza B (43%) and influenza A (H1N1) (41%) was evident. A high proportion of cases was reported in children <2 years 274 (37%). The proportional contribution of influenza-associated SARI to all-cause hospital admissions was high in children <2 years in the south (4.5% [95% CI: 3.1-6.5]) and in children <5 years in Beirut (0.7% [95% CI: 0.6-0.8]). This is the first study to highlight the proportion of influenza-associated SARI in 2 hospitals in Lebanon. The findings will be beneficial for supporting respiratory prevention and immunization program policies. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Characterization of cross protection of Swine-Origin Influenza Virus (S-OIV) H1N1 and reassortant H5N1 influenza vaccine in BALB/c mice given a single-dose vaccination

PubMed Central

2013-01-01

Background Influenza virus has antigen drift and antigen shift effect, vaccination with some influenza vaccine might not induce sufficient immunity for host to the threat of other influenza virus strains. S-OIV H1N1 and H5N1 influenza vaccines in single-dose immunization were evaluated in mice for cross protection to the challenge of A/California/7/2009 H1N1 or NIBRG-14 H5N1 virus. Results Both H1N1 and H5N1 induced significant homologous IgG, HAI, and microneutralization antibody responses in the mice, while only vaccines plus adjuvant produced significant heterogeneous IgG and HAI antibody responses. Both alum and MPLA adjuvants significantly reduced the S-OIV H1N1 vaccine dose required to elicit protective HAI antibody titers from 0.05 μg to 0.001 μg. Vaccines alone did not protect mice from challenge with heterogeneous influenza virus, while H5N1 vaccine plus alum and MPLA adjuvants did. Mouse body weight loss was also less significant in the presence of adjuvant than in the vaccine without adjuvant. Furthermore, both H1N1 and H5N1 lung viral titers of immunized mice were significantly reduced post challenge with homologous viruses. Conclusion Only in the presence of MPLA adjuvant could the H5N1 vaccine significantly reduce mouse lung viral titers post H1N1 virus challenge, and not vice versa. MPLA adjuvant induced cross protection with a single dose vaccination to the challenge of heterogeneous influenza virus in mice. Lung viral titer seemed to be a better indicator compared to IgG, neutralization antibody, and HAI titer to predict survival of mice infected with influenza virus. PMID:23517052

Use of a mandatory declination form in a program for influenza vaccination of healthcare workers.

PubMed

Ribner, Bruce S; Hall, Cynthia; Steinberg, James P; Bornstein, William A; Chakkalakal, Rosette; Emamifar, Amir; Eichel, Irving; Lee, Peter C; Castellano, Penny Z; Grossman, Gilbert D

2008-04-01

To evaluate the utility and impact of using a declination form in the context of an influenza immunization program for healthcare workers. A combined form for documentation of vaccination consent, medical contraindication(s) for vaccination, or vaccination declination was used during the 2006-2007 influenza season in a healthcare system employing approximately 9,200 nonphysician employees in 3 hospitals; a skilled nursing care facility; a large, multisite, faculty-practice plan; and an administrative building. Responses were entered into a database that contained files from human resources departments, which allowed correlation with job category and work location. The overall levels of influenza vaccination coverage of employees increased from 43% (3,892 of 9,050) during the 2005-2006 season to 66.5% (6,123 of 9,214) during the 2006-2007 season. Of 9,214 employees, 1,898 (20.6%) signed the declination statement. Among the occupation groups, nurses had the lowest rate of declining vaccination (13.2% [393 of 2,970]; P < .0001), followed by pharmacy personnel (18.1% [40 of 221]), ancillary personnel with frequent patient contact (21.9% [169 of 771), and all others (24.7% [1,296 of 5,252]). Among the employees who declined vaccination, nurses were the least likely to select the reasons "afraid of needles" (3.8% [15 of 393], vs. 9.1% [137 of 1,505] for all other groups; P < .001) and "fear of getting influenza from the vaccine" (13.5% [53 of 393], vs. 20.5% [309 of 1,505]; P = .002). Seven pregnant nurses had been advised by their obstetricians to avoid vaccination. When declination of influenza vaccination was analyzed by age, 16% of personnel (797 of 4,980) 50 years of age and older declined to be vaccinated, compared with 26% of personnel (1,101 of 4,234) younger than 50 years of age (P < .0001). Implementing use of the declination form during the 2006-2007 influenza season was one of several measures that led to a 55% increase in the acceptance of influenza vaccination by healthcare workers in our healthcare system. Although we cannot determine to what degree use of the declination form contributed to the increased rate of vaccination, use of this form helped the vaccination program assess the reasons for declination and will help to focus future vaccination campaigns.

Demographic and spatiotemporal patterns of avian influenza infection at the continental scale, and in relation to annual life cycle of a migratory host

USGS Publications Warehouse

Nallar, Rodolfo; Papp, Zsuzsanna; Epp, Tasha; Leighton, Frederick A.; Swafford, Seth R.; DeLiberto, Thomas J.; Dusek, Robert J.; Ip, Hon S.; Hall, Jeffrey S.; Berhane, Yohannes; Gibbs, Samantha E.J.; Soos, Catherine

2015-01-01

Since the spread of highly pathogenic avian influenza (HPAI) H5N1 in the eastern hemisphere, numerous surveillance programs and studies have been undertaken to detect the occurrence, distribution, or spread of avian influenza viruses (AIV) in wild bird populations worldwide. To identify demographic determinants and spatiotemporal patterns of AIV infection in long distance migratory waterfowl in North America, we fitted generalized linear models with binominal distribution to analyze results from 13,574 blue-winged teal (Anas discors, BWTE) sampled in 2007 to 2010 year round during AIV surveillance programs in Canada and the United States. Our analyses revealed that during late summer staging (July-August) and fall migration (September-October), hatch year (HY) birds were more likely to be infected than after hatch year (AHY) birds, however there was no difference between age categories for the remainder of the year (winter, spring migration, and breeding period), likely due to maturing immune systems and newly acquired immunity of HY birds. Probability of infection increased non-linearly with latitude, and was highest in late summer prior to fall migration when densities of birds and the proportion of susceptible HY birds in the population are highest. Birds in the Central and Mississippi flyways were more likely to be infected compared to those in the Atlantic flyway. Seasonal cycles and spatial variation of AIV infection were largely driven by the dynamics of AIV infection in HY birds, which had more prominent cycles and spatial variation in infection compared to AHY birds. Our results demonstrate demographic as well as seasonal, latitudinal and flyway trends across Canada and the US, while illustrating the importance of migratory host life cycle and age in driving cyclical patterns of prevalence.

Ubiquitin in Influenza Virus Entry and Innate Immunity.

PubMed

Rudnicka, Alina; Yamauchi, Yohei

2016-10-24

Viruses are obligatory cellular parasites. Their mission is to enter a host cell, to transfer the viral genome, and to replicate progeny whilst diverting cellular immunity. The role of ubiquitin is to regulate fundamental cellular processes such as endocytosis, protein degradation, and immune signaling. Many viruses including influenza A virus (IAV) usurp ubiquitination and ubiquitin-like modifications to establish infection. In this focused review, we discuss how ubiquitin and unanchored ubiquitin regulate IAV host cell entry, and how histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase with ubiquitin-binding activity, mediates IAV capsid uncoating. We also discuss the roles of ubiquitin in innate immunity and its implications in the IAV life cycle.

Ubiquitin in Influenza Virus Entry and Innate Immunity

PubMed Central

Rudnicka, Alina; Yamauchi, Yohei

2016-01-01

Viruses are obligatory cellular parasites. Their mission is to enter a host cell, to transfer the viral genome, and to replicate progeny whilst diverting cellular immunity. The role of ubiquitin is to regulate fundamental cellular processes such as endocytosis, protein degradation, and immune signaling. Many viruses including influenza A virus (IAV) usurp ubiquitination and ubiquitin-like modifications to establish infection. In this focused review, we discuss how ubiquitin and unanchored ubiquitin regulate IAV host cell entry, and how histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase with ubiquitin-binding activity, mediates IAV capsid uncoating. We also discuss the roles of ubiquitin in innate immunity and its implications in the IAV life cycle. PMID:27783058

Antibody responses to natural influenza A/H1N1/09 disease or following immunization with adjuvanted vaccines, in immunocompetent and immunocompromised children.

PubMed

Meier, Sara; Bel, Michael; L'huillier, Arnaud; Crisinel, Pierre-Alex; Combescure, Christophe; Kaiser, Laurent; Grillet, Stéphane; Pósfay-Barbe, Klara; Siegrist, Claire-Anne

2011-04-27

To compare antibody responses elicited by influenza A/H1N1/09 disease and immunization with adjuvanted vaccines, in immunocompetent or immunocompromised children. Prospective parallel cohort field study enrolling children with confirmed influenza A/H1N1/09 disease or immunized with 1 (immunocompetent) or 2 (immunocompromised) doses of influenza A/H1N1/09 squalene-based AS03- or MF59-adjuvanted vaccines. Antibody geometric mean titers (GMT) were measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays 4-6 weeks after vaccination/disease. Vaccine adverse events were self-recorded in a 7-day diary. Antibody titers were as high in 48 immunocompetent children after a single immunization (HAI and MN seroprotection rates: 98%; HAI-GMT: 395, MN-GMT: 370) as in 51 convalescent children (seroprotection rates: 98% (HAI) and 92% (MN); GMT: 350 (HAI) and 212 (MN). Twenty-seven immunocompromised children reached slightly lower seroprotection rates (HAI: 89%, MN: 85%) but similar antibody titers (HAI-GMT: 306, MN-GMT: 225) after 2 immunizations. Adverse events increased with age (P=0.01) and were more frequent with Pandemrix® than Focetria® (P=0.03). Similarly high seroresponses may be expected in immunocompetent children after a single dose of adjuvanted vaccines as responses of convalescent children. Two vaccine doses were sufficient for most immunocompromised children. NCT0102293 and NCT01022905. Copyright © 2011 Elsevier Ltd. All rights reserved.

Influenza, immune system, and pregnancy.

PubMed

Raj, Renju S; Bonney, Elizabeth A; Phillippe, Mark

2014-12-01

Influenza is a major health problem worldwide. Both seasonal influenza and pandemics take a major toll on the health and economy of our country. The present review focuses on the virology and complex immunology of this RNA virus in general and in relation to pregnancy. The goal is to attempt to explain the increased morbidity and mortality seen in infection during pregnancy. We discuss elements of innate and adaptive immunity as well as placental cellular responses to infection. In addition, we delineate findings in animal models as well as human disease. Increased knowledge of maternal and fetal immunologic responses to influenza is needed. However, enhanced understanding of nonimmune, pregnancy-specific factors influencing direct interaction of the virus with host cells is also important for the development of more effective prevention and treatment options in the future. © The Author(s) 2014.

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

PubMed Central

Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia; Krause, Jens C.; Klemenc, Jennifer; Zea, Johanna; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P.; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M.; Chappell, James D.; Crowe, James E.; Williams, John V.; Melendi, Guillermina A.; Polack, Fernando P.

2010-01-01

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

Influenza virus exploits tunneling nanotubes for cell-to-cell spread

PubMed Central

Kumar, Amrita; Kim, Jin Hyang; Ranjan, Priya; Metcalfe, Maureen G.; Cao, Weiping; Mishina, Margarita; Gangappa, Shivaprakash; Guo, Zhu; Boyden, Edward S.; Zaki, Sherif; York, Ian; García-Sastre, Adolfo; Shaw, Michael; Sambhara, Suryaprakash

2017-01-01

Tunneling nanotubes (TNTs) represent a novel route of intercellular communication. While previous work has shown that TNTs facilitate the exchange of viral or prion proteins from infected to naïve cells, it is not clear whether the viral genome is also transferred via this mechanism and further, whether transfer via this route can result in productive replication of the infectious agents in the recipient cell. Here we present evidence that lung epithelial cells are connected by TNTs, and in spite of the presence of neutralizing antibodies and an antiviral agent, Oseltamivir, influenza virus can exploit these networks to transfer viral proteins and genome from the infected to naïve cell, resulting in productive viral replication in the naïve cells. These observations indicate that influenza viruses can spread using these intercellular networks that connect epithelial cells, evading immune and antiviral defenses and provide an explanation for the incidence of influenza infections even in influenza-immune individuals and vaccine failures. PMID:28059146

Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain

PubMed Central

Steel, John; Lowen, Anice C.; Wang, Taia T.; Yondola, Mark; Gao, Qinshan; Haye, Kester; García-Sastre, Adolfo; Palese, Peter

2010-01-01

ABSTRACT Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine. PMID:20689752

The duck genome and transcriptome provide insight into an avian influenza virus reservoir species

PubMed Central

Chen, Hualan; Zhang, Yong; Qian, Wubin; Kim, Heebal; Gan, Shangquan; Zhao, Yiqiang; Li, Jianwen; Yi, Kang; Feng, Huapeng; Zhu, Pengyang; Li, Bo; Liu, Qiuyue; Fairley, Suan; Magor, Katharine E; Du, Zhenlin; Hu, Xiaoxiang; Goodman, Laurie; Tafer, Hakim; Vignal, Alain; Lee, Taeheon; Kim, Kyu-Won; Sheng, Zheya; An, Yang; Searle, Steve; Herrero, Javier; Groenen, Martien A M; Crooijmans, Richard P M A; Faraut, Thomas; Cai, Qingle; Webster, Robert G; Aldridge, Jerry R; Warren, Wesley C; Bartschat, Sebastian; Kehr, Stephanie; Marz, Manja; Stadler, Peter F; Smith, Jacqueline; Kraus, Robert H S; Zhao, Yaofeng; Ren, Liming; Fei, Jing; Morisson, Mireille; Kaiser, Pete; Griffin, Darren K; Rao, Man; Pitel, Frederique; Wang, Jun; Li, Ning

2014-01-01

The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck’s defense mechanisms against influenza infection have been optimized through the diversification of its β-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses. PMID:23749191

Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

PubMed

Quach, Caroline

2014-12-01

Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Canadian influenza decision, 1976.

PubMed Central

Morrison, A. B.; Liston, A. J.; Abbott, J. D.

1976-01-01

This paper explains the Canadian decision process following the isolation and identification of A/New Jersey/8/76 at Fort Dix, New Jersey in February 1976. The cause for concern was the emergence of a swine-like strain related to that which caused the 1918-19 pandemic, together with proved man-to-man transmission. This concern was reinforced since all new influenza A strains known to have infected the number of persons involved at Fort Dix have become strains of epidemic importance. The Fort Dix outbreak gave sufficient warning to allow implementation of a national vaccination program, to prevent and protect against influenza. In the past such an opportunity had not occurred, and vaccine use had, at best, constituted an intervention in the course of an outbreak. The National Advisory Committee on Immunizing Agents had all available information when it reached its decision to recommend vaccination with bivalent (A/Victoria and A/New Jersey) or with monovalent (A/New Jersey) vaccine for selective, high-risk groups. This was an independent, scientifically based decision. PMID:991022

Pan-Canadian assessment of pandemic immunization data collection: study methodology

PubMed Central

2010-01-01

Background The collection of individual-level pandemic (H1N1) 2009 influenza immunization data was considered important to facilitate optimal vaccine delivery and accurate assessment of vaccine coverage. These data are also critical for research aimed at evaluating the new vaccine's safety and effectiveness. Systems used to collect immunization data include manual approaches in which data are collected and retained on paper, electronic systems in which data are captured on computer at the point of vaccination and hybrid systems which are comprised of both computerized and manual data collection components. This study's objective was to compare the efficiencies and perceptions of data collection methods employed during Canada's pandemic (H1N1) 2009 influenza vaccination campaign. Methods/Design A pan-Canadian observational study was conducted in a convenience sample of public health clinics and healthcare institutions during the H1N1 vaccination campaign in the fall of 2009. The study design consisted of three stages: Stage 1 involved passive observation of the site's layout, processes and client flow; Stage 2 entailed timing site staff on 20 clients through five core immunization tasks: i) client registration, ii) medical history collection, iii) medical history review, iv) vaccine administration record keeping and v) preparation of proof of vaccine administration for the client; in Stage 3, site staff completed a questionnaire regarding perceived usability of the site's data collection approach. Before the national study began, a pilot study was conducted in three seasonal influenza vaccination sites in Ontario, to both test that the proposed methodology was logistically feasible and to determine inter-rater reliability in the measurements of the research staff. Comparative analyses will be conducted across the range of data collection methods with respect to time required to collect immunization data, number and type of individual-level data elements collected, and clinic staff perceptions of the usability of the method employed at their site, using analysis of variance (ANOVA). Discussion Various data collection methods were employed at immunization sites across Canada during the pandemic (H1N1) 2009 influenza vaccination campaign. Our comparison of methods can facilitate planning an efficient, coordinated approach for collecting immunization data in future influenza seasons. PMID:20624270

Pan-Canadian assessment of pandemic immunization data collection: study methodology.

PubMed

Pereira, Jennifer A; Quach, Susan; Heidebrecht, Christine; Foisy, Julie; Quan, Sherman; Finkelstein, Michael; Sikora, Christopher A; Bettinger, Julie A; Buckeridge, David L; McCarthy, Anne; Deeks, Shelley; Kwong, Jeffrey C

2010-06-08

The collection of individual-level pandemic (H1N1) 2009 influenza immunization data was considered important to facilitate optimal vaccine delivery and accurate assessment of vaccine coverage. These data are also critical for research aimed at evaluating the new vaccine's safety and effectiveness. Systems used to collect immunization data include manual approaches in which data are collected and retained on paper, electronic systems in which data are captured on computer at the point of vaccination and hybrid systems which are comprised of both computerized and manual data collection components. This study's objective was to compare the efficiencies and perceptions of data collection methods employed during Canada's pandemic (H1N1) 2009 influenza vaccination campaign. A pan-Canadian observational study was conducted in a convenience sample of public health clinics and healthcare institutions during the H1N1 vaccination campaign in the fall of 2009. The study design consisted of three stages: Stage 1 involved passive observation of the site's layout, processes and client flow; Stage 2 entailed timing site staff on 20 clients through five core immunization tasks: i) client registration, ii) medical history collection, iii) medical history review, iv) vaccine administration record keeping and v) preparation of proof of vaccine administration for the client; in Stage 3, site staff completed a questionnaire regarding perceived usability of the site's data collection approach. Before the national study began, a pilot study was conducted in three seasonal influenza vaccination sites in Ontario, to both test that the proposed methodology was logistically feasible and to determine inter-rater reliability in the measurements of the research staff. Comparative analyses will be conducted across the range of data collection methods with respect to time required to collect immunization data, number and type of individual-level data elements collected, and clinic staff perceptions of the usability of the method employed at their site, using analysis of variance (ANOVA). Various data collection methods were employed at immunization sites across Canada during the pandemic (H1N1) 2009 influenza vaccination campaign. Our comparison of methods can facilitate planning an efficient, coordinated approach for collecting immunization data in future influenza seasons.

The time-associated impact of the Newborn Influenza Protection Act on infant influenza rates in New York State.

PubMed

Shah, Shetal; Messina, Catherine

2014-11-01

Influenza presents with increased morbidity and mortality in children ≤5 months of age. Vaccination of caregivers is indicated, but immunization rates are estimated at only 30%. The 2009 New York State Neonatal Influenza Protection Act (NIPA) mandated offering of influenza vaccine to caregivers during the post-partum hospitalization. The purpose of this study was to determine the impact of NIPA on infant influenza rates. Data on laboratory-confirmed influenza cases between 2006 and 2012 were extracted from the New York State Electronic Clinical Laboratory Reporting System (ECLRS). Data on infant cases were categorized by age (0-5 months) and location [New York City (NYC), outside NYC] based on reporting laboratory site. The total number of influenza cases and the percentage of total cases in the infant age group were normalized to the number of reporting laboratory sites. The χ2-test was used to compare the proportions of cases pre- and post-implementation. Year-to-year trends were assessed by linear regression. All tests of significance were two-sided and evaluated at the P<0.05 level. During the 6-year study period, 3154 cases of infant influenza were detected. In bivariate analysis, 1707 (54.1%) of cases occurred prior to NIPA implementation and 1447 (45.9%) of cases occurred after (P<0.001). Of the 1422 total infant cases detected in NYC, the percentages of influenza cases pre- and post-NIPA were 54.6% (777) and 45.4% (645), respectively (P<0.006). Outside NYC, the percentage of infant cases was reduced from 53.7% (930/1732) to 46.3% (802/1732, P<0.02). Prior to implementation, there was a year-to-year increase in the number of infant influenza cases statewide (P<0.04 for trend). The ratio of infant influenza cases normalized per ECLRS site in NYC increased each year after NIPA passage (P<0.01 for trend). The ratio of infant cases outside NYC decreased annually (P<0.05 for trend). No year-to-year trends were seen in the percentage of total influenza cases in the infant age group compared to total cases across all age groups either within or outside NYC. Comparison of three influenza seasons before and after NIPA suggests a total statewide reduction in infant influenza. However, the greatest driver of this reduction occurs from reduced disease in infants outside NYC. We speculate that, with increased crowding within NYC, parental immunization as encouraged by NIPA may not create cocoon immunity.

Expression of H5 hemagglutinin vaccine antigen in common duckweed (Lemna minor) protects against H5N1 high pathogenicity avian influenza virus challenge in immunized chickens

USDA-ARS?s Scientific Manuscript database

A synthetic hemagglutinin (HA) gene from the highly pathogenic avian influenza (HPAI) virus A/chicken/Indonesia/7/2003 (H5N1) (Indo/03) was expressed in aquatic plant Lemna minor (rLemna-HA). In Experiment 1, efficacy of rLemna-HA was tested on specific pathogen free (SPF) birds immunized with 0.2 ...

Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice.

PubMed

Pazos, Michael A; Kraus, Thomas A; Muñoz-Fontela, César; Moran, Thomas M

2012-01-01

Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.

mTOR modulates the antibody response to provide cross-protective immunity to lethal influenza infections

PubMed Central

Keating, Rachael; Hertz, Tomer; Wehenkel, Marie; Harris, Tarsha L.; Edwards, Benjamin A.; McClaren, Jennifer L.; Brown, Scott A.; Surman, Sherri; Wilson, Zachary S.; Bradley, Philip; Hurwitz, Julia; Chi, Hongbo; Doherty, Peter C.; Thomas, Paul G.; McGargill, Maureen A.

2013-01-01

Highly pathogenic avian influenza viruses pose a continuing global threat. Current vaccines will not protect against novel pandemic viruses. Creating “universal” vaccines has been unsuccessful because the immunological mechanisms promoting heterosubtypic immunity are incompletely defined. We show that rapamycin, an immunosuppressive drug that inhibits mTOR, promotes cross-strain protection against lethal H5N1 and H7N9 infections when administered during H3N2 virus immunization. Rapamycin reduced germinal center formation and inhibited B cell class-switching, yielding a unique repertoire of antibodies that mediated heterosubtypic protection. Our data establish a requirement for mTORC1 in B cell class-switching and demonstrate that rapamycin skews the antibody response away from high affinity variant epitopes, targeting more conserved elements of hemagglutinin. These findings have intriguing implications for influenza vaccine design. PMID:24141387

Added Value of Avian Influenza (H5) Day-Old Chick Vaccination for Disease Control in Egypt.

PubMed

Peyre, Marisa; Choisy, Marc; Sobhy, Heba; Kilany, Walid H; Gély, Marie; Tripodi, Astrid; Dauphin, Gwenaëlle; Saad, Mona; Roger, François; Lubroth, Juan; Jobre, Yilma

2016-05-01

The immunity profile against H5N1 highly pathogenic avian influenza (HPAI) in the commercial poultry value chain network in Egypt was modeled with the use of different vaccination scenarios. The model estimated the vaccination coverage, the protective seroconversion level, and the duration of immunity for each node of the network and vaccination scenario. Partial budget analysis was used to compare the benefit-cost of the different vaccination scenarios. The model predicted that targeting day-old chick avian influenza (AI) vaccination in industrial and large hatcheries would increase immunity levels in the overall poultry population in Egypt and especially in small commercial poultry farms (from <30% to >60%). This strategy was shown to be more efficient than the current strategy of using inactivated vaccines. Improving HPAI control in the commercial poultry sector in Egypt would have a positive impact to improve disease control.

The innate and adaptive immune response to avian influenza virus

USDA-ARS?s Scientific Manuscript database

Protective immunity against viruses is mediated by the early innate immune responses and later on by the adaptive immune responses. The early innate immunity is designed to contain and limit virus replication in the host, primarily through cytokine and interferon production. Most all cells are cap...

Combining evidence and diffusion of innovation theory to enhance influenza immunization.

PubMed

Britto, Maria T; Pandzik, Geralyn M; Meeks, Connie S; Kotagal, Uma R

2006-08-01

Children and adolescents with chronic conditions such as asthma, diabetes, and HIV are at high risk of influenza-related morbidity, and there are recommendations to immunize these populations annually. At Cincinnati Children's Hospital Medical Center, the influenza immunization rate increased to 90.4% (5% declined) among 200 patients with cystic fibrosis (CF). Diffusion of innovation theory was used to guide the design and implementation of spread to other clinics. The main intervention strategies were: (1) engagement of interested, nurse-led teams, (2) A collaborative learning session, (3) A tool kit including literature, sample goals, reminder postcards, communication strategies, and team member roles and processes, (4) open-access scheduling and standing orders (5) A simple Web-based registry, (6) facilitated vaccine ordering, (7) recall phone calls, and (8) weekly results posting. Clinic-specific immunization rates ranged from 32.7% to 92.8%, with the highest rate reported in the CF clinic. All teams used multiple strategies; with six of the seven using four or more. Overall, 60.0% (762/1,269) of the population was immunized. Barriers included vaccine shortages, lack of time for reminder calls, and lack of physician support in one clinic. A combination of interventions, guided by evidence and diffusion of innovation theory, led to immunization rates higher than those reported in the literature.

Using administrative claims to identify children with chronic conditions in a statewide immunization registry.

PubMed

Dombkowski, Kevin J; Costello, Lauren; Dong, Shiming; Clark, Sarah J

2014-05-01

To demonstrate the feasibility and utility of using administrative claims data from commercial health plans to establish a high-risk indicator in a statewide immunization registry for enrollees with chronic conditions. Retrospective cohort analysis. Administrative data were used to identify children with 1 or more chronic conditions enrolled in 2 commercial health plans during the 2008-2009 and 2009-2010 influenza seasons and matched with a statewide immunization registry. The proportion of cases that successfully matched and historical health services utilization, including influenza vaccinations and missed opportunities, were assessed. A total of 93% of children with chronic conditions identified through administrative claims were successfully matched with the statewide registry. Less than one-third of children received the seasonal influenza vaccine in either the 2008-2009 (29%) or 2009-2010 (32%) seasons; 30% of children received the H1N1 vaccination in 2009-2010. Most children in the 2008-2009 (63%) and 2009-2010 (63%) seasons had at least 1 missed opportunity for seasonal influenza vaccination. Younger children had the highest percentage of missed opportunities while adolescents had the lowest rate of missed opportunities for vaccination. Conclusions It is feasible to identify children with chronic conditions using administrative data and to link them with a statewide immunization registry. Low influenza vaccination rates and high occurrences of missed opportunities among children with chronic conditions suggest the utility of integrating administrative claims data with statewide registries to support various outreach mechanisms, including physician-focused and parent-targeted reminder/recall, based on target age to improve vaccination rates.

Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals.

PubMed

Ovsyannikova, Inna G; White, Sarah J; Larrabee, Beth R; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

2014-02-07

Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (50-74 years old) who were immunized with inactivated TIV influenza vaccine that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r=0.23, p=0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p=0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Built-in adjuvanticity of genetically and protein-engineered chimeric molecules for targeting of influenza A peptide epitopes.

PubMed

Kerekov, Nikola S; Ivanova, Iva I; Mihaylova, Nikolina M; Nikolova, Maria; Prechl, Jozsef; Tchorbanov, Andrey I

2014-10-01

Highly purified, subunit, or synthetic viral antigens are known to be weakly immunogenic and potentate only the antibody, rather than cell-mediated immune responses. An alternative approach for inducing protective immunity with small viral peptides would be the direct targeting of viral epitopes to the immunocompetent cells by DNA vaccines encoding antibody fragments specific to activating cell surface co-receptor molecules. Here, we are exploring as a new genetic vaccine, a DNA chimeric molecule encoding a T and B cell epitope-containing influenza A virus hemagglutinin peptide joined to sequences encoding a single-chain variable fragment antibody fragment specific for the costimulatory B cell complement receptors 1 and 2. This recombinant DNA molecule was inserted into eukaryotic expression vector and used as a naked DNA vaccine in WT and CR1/2 KO mice. The intramuscular administration of the DNA construct resulted in the in vivo expression of an immunogenic chimeric protein, which cross-links cell surface receptors on influenza-specific B cells. The DNA vaccination was followed by prime-boosting with the protein-engineered replica of the DNA construct, thus delivering an activation intracellular signal. Immunization with an expression vector containing the described construct and boosting with the protein chimera induced a strong anti-influenza cytotoxic response, modulation of cytokine profile, and a weak antibody response in Balb/c mice. The same immunization scheme did not result in generation of influenza-specific response in mice lacking the target receptor, underlining the molecular adjuvant effect of receptor targeting.

Surveillance and compensation claims for adverse events following immunization from 2011 to 2016 in the Republic of Korea.

PubMed

Kim, Min-Kyung; Lee, Yeon Kyeong; Kim, Tae Eun; Kong, Insik; Yang, Hyeon-Jong; Suh, Eun Sook

2017-07-01

In recent years, research on reported adverse events following immunization (AEFI) and claims filed for compensation has been lacking. We reviewed reported AEFIs and compensation claims in Korea from 2011 to 2016. We listed all of the AEFI registered in the Integrated Management System of Disease and Public Health and reviewed the list of claims filed and serious AEFIs reported from 2011 to 2016. An average of 278 AEFI cases was reported annually from 2011 to 2016. Of these, 31 deaths were reported. However, there was no association found between these deaths and vaccinations when evaluating vaccine lot, reviewing autopsies, and considering underlying diseases. AEFI reporting rate was as high as 20.8 cases for bacillus Calmette-Guérin (BCG) vaccine, 7.3 cases for 23-valent pneumococcal polysaccharide vaccine (PPV23), and 5.4 cases for human papillomavirus vaccine per 100,000 vaccination doses in 2016. Of the 469 total cases that claimed vaccine injury compensation from 2011 to 2016, the BCG vaccine was most commonly involved, with 235 cases (50%), followed by influenza vaccine and PPV23, with 90 and 55 cases, respectively. Of these cases, 96% of BCG-related AEFI were compensated, while only 31% and 49% of AEFI following influenza and PPV23 vaccination, respectively, were compensated. Common characteristics of uncompensated cases included the elderly subjects, receiving influenza vaccine, having underlying disease, or a very short time interval between vaccination and symptoms. We have maintained vaccine safety management system through both rapid response to serious AEFI and vaccine injury compensation in order to sustain public trust in the National Immunization Program.

School-Located Influenza Vaccination and Absenteeism among Elementary School Students in a Hispanic Community

ERIC Educational Resources Information Center

Keck, Patricia C.; Ynalvez, Marcus Antonius; Gonzalez, Hector F.; Castillo, Keila D.

2013-01-01

Seasonal influenza is recognized as a significant health burden to children and is a cause of excess school absenteeism in children. In 2008, the Advisory Committee on Immunization Practices recommended annual influenza vaccination for all children 6 months to 18 years of age. School nurses influence participation in this recommendation by…

Cross reactive antibody and cytotoxic T lymphocytes from avian influenza H9N2 infected chickens against homologous and heterologous avian influenza isolates

USDA-ARS?s Scientific Manuscript database

Immunity against avian influenza (AI) is largely based on the induction of neutralizing antibodies produced against the hemagglutinin, although cytotoxic T lymphocytes (CTL’s) have been reported as critical for clearance of virus from infected cells. Antibody production against a particular virus ...

Playing Hide and Seek: How Glycosylation of the Influenza Virus Hemagglutinin Can Modulate the Immune Response to Infection

PubMed Central

Tate, Michelle D.; Job, Emma R.; Deng, Yi-Mo; Gunalan, Vithiagaran; Maurer-Stroh, Sebastian; Reading, Patrick C.

2014-01-01

Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the hemagglutinin (HA) glycoprotein. The viral HA is the major target recognized by neutralizing antibodies and glycans have been proposed to shield antigenic sites on HA, thereby promoting virus survival in the face of widespread vaccination and/or infection. However, addition of glycans can also interfere with the receptor binding properties of HA and this must be compensated for by additional mutations, creating a fitness barrier to accumulation of glycosylation sites. In addition, glycans on HA are also recognized by phylogenetically ancient lectins of the innate immune system and the benefit provided by evasion of humoral immunity is balanced by attenuation of infection. Therefore, a fine balance must exist regarding the optimal pattern of HA glycosylation to offset competing pressures associated with recognition by innate defenses, evasion of humoral immunity and maintenance of virus fitness. In this review, we examine HA glycosylation patterns of IAV associated with pandemic and seasonal influenza and discuss recent advancements in our understanding of interactions between IAV glycans and components of innate and adaptive immunity. PMID:24638204

Trivalent live attenuated intranasal influenza vaccine administered during the 2003-2004 influenza type A (H3N2) outbreak provided immediate, direct, and indirect protection in children.

PubMed

Piedra, Pedro A; Gaglani, Manjusha J; Kozinetz, Claudia A; Herschler, Gayla B; Fewlass, Charles; Harvey, Dianne; Zimmerman, Nadine; Glezen, W Paul

2007-09-01

Live attenuated influenza vaccine may protect against wild-type influenza illness shortly after vaccine administration by innate immunity. The 2003-2004 influenza A (H3N2) outbreak arrived early, and the circulating strain was antigenically distinct from the vaccine strain. The objective of this study was to determine the effectiveness of influenza vaccines for healthy school-aged children when administered during the influenza outbreak. An open-labeled, nonrandomized, community-based influenza vaccine trial was conducted in children 5 to 18 years old. Age-eligible healthy children received trivalent live attenuated influenza vaccine. Trivalent inactivated influenza vaccine was given to children with underlying health conditions. Influenza-positive illness was compared between vaccinated and nonvaccinated children. Medically attended acute respiratory illness and pneumonia and influenza rates for Scott and White Health Plan vaccinees were compared with age-eligible Scott and White Health Plan nonparticipants in the intervention communities. Herd protection was assessed by comparing age-specific medically attended acute respiratory illness rates in Scott and White Health Plan members in the intervention and comparison communities. We administered 1 dose of trivalent live attenuated influenza vaccine or trivalent inactivated influenza vaccine to 6569 and 1040 children, respectively (31.5% vaccination coverage), from October 10 to December 30, 2003. The influenza outbreak occurred from October 12 to December 20, 2003. Significant protection against influenza-positive illness (37.3%) and pneumonia and influenza events (50%) was detected in children who received trivalent live attenuated influenza vaccine but not trivalent inactivated influenza vaccine. Trivalent live attenuated influenza vaccine recipients had similar protection against influenza-positive illness within 14 days compared with >14 days (10 of 25 vs 9 of 30) after vaccination. Indirect effectiveness against medically attended acute respiratory illness was detected in children 5 to 11 and adults 35 to 44 years of age. One dose of trivalent live attenuated influenza vaccine was efficacious in children even when administered during an influenza outbreak and when the dominant circulating influenza virus was antigenically distinct from the vaccine strain. We hypothesize that trivalent live attenuated influenza vaccine provides protection against influenza by both innate and adaptive immune mechanisms.

Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection

PubMed Central

Duan, Susu; Thomas, Paul G.

2016-01-01

Influenza A virus (IAV) is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL)-mediated immunity contributes to the clearance of virus-infected cells, and CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, its cytotoxicity, and the effects of produced proinflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL antiviral immunity from those necessary to restrain CTL-mediated non-specific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity. PMID:26904022

Modeling human influenza infection in the laboratory

PubMed Central

Radigan, Kathryn A; Misharin, Alexander V; Chi, Monica; Budinger, GR Scott

2015-01-01

Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection. PMID:26357484

Immune response to influenza vaccine in children with inflammatory bowel disease

PubMed Central

Lu, Ying; Jacobson, Denise L.; Ashworth, Lori A.; Grand, Richard J.; Meyer, Anthony L.; McNeal, Monica M.; Gregas, Matt C.; Burchett, Sandra K.; Bousvaros, Athos

2013-01-01

OBJECTIVE Patients with inflammatory bowel disease (IBD) frequently receive immunosuppressive therapy. The immune response in these patients to vaccines has not been well studied. We conducted a prospective, open label study to evaluate the serologic response to influenza vaccine in children with IBD. METHODS Serum was obtained from 146 children and young adults with IBD (96 CD, 47 UC, 3 IC) for baseline influenza titer, immediately followed by immunization with trivalent [A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (B)] inactivated influenza vaccine. Subjects returned for repeat titers 3-9 weeks later. Seroprotection against each influenza strain was defined as hemagglutination inhibition (HAI) titer ≥40. Patients were categorized as non-immunosuppressed [(NIS), aminosalicylates only, antibiotics only, or no therapy] or immunosuppressed [(IS), any immunosuppressive agent]. IS patients were further subcategorized as: (1) tacrolimus; (2) TNF-alpha inhibitor; (3) immunomodulator; and (4) corticosteroids only. RESULTS More patients were seroprotected against strains A/H1N1 and A/H3N2 than B strain (p<0.02), regardless of immunosuppression status. The proportion seroprotected and geometric mean titers at post-vaccination were similar between NIS and IS groups for all three strains. Subanalysis of patients not seroprotected at baseline showed that those receiving anti-TNF therapy were less likely seroprotected against strain B (14%) compared to patients in the NIS group (39%, p=0.025). There were no serious vaccine-associated adverse events. CONCLUSION Influenza vaccination produces a high prevalence of seroprotection in IBD patients, particularly against A strains. The vaccine is well tolerated. Routine influenza vaccination in IBD patients is recommended, irrespective of whether patients receive immunosuppressive medications. PMID:19174786

Optimal H1N1 vaccination strategies based on self-interest versus group interest.

PubMed

Shim, Eunha; Meyers, Lauren Ancel; Galvani, Alison P

2011-02-25

Influenza vaccination is vital for reducing H1N1 infection-mediated morbidity and mortality. To reduce transmission and achieve herd immunity during the initial 2009-2010 pandemic season, the US Centers for Disease Control and Prevention (CDC) recommended that initial priority for H1N1 vaccines be given to individuals under age 25, as these individuals are more likely to spread influenza than older adults. However, due to significant delay in vaccine delivery for the H1N1 influenza pandemic, a large fraction of population was exposed to the H1N1 virus and thereby obtained immunity prior to the wide availability of vaccines. This exposure affects the spread of the disease and needs to be considered when prioritizing vaccine distribution. To determine optimal H1N1 vaccine distributions based on individual self-interest versus population interest, we constructed a game theoretical age-structured model of influenza transmission and considered the impact of delayed vaccination. Our results indicate that if individuals decide to vaccinate according to self-interest, the resulting optimal vaccination strategy would prioritize adults of age 25 to 49 followed by either preschool-age children before the pandemic peak or older adults (age 50-64) at the pandemic peak. In contrast, the vaccine allocation strategy that is optimal for the population as a whole would prioritize individuals of ages 5 to 64 to curb a growing pandemic regardless of the timing of the vaccination program. Our results indicate that for a delayed vaccine distribution, the priorities that are optimal at a population level do not align with those that are optimal according to individual self-interest. Moreover, the discordance between the optimal vaccine distributions based on individual self-interest and those based on population interest is even more pronounced when vaccine availability is delayed. To determine optimal vaccine allocation for pandemic influenza, public health agencies need to consider both the changes in infection risks among age groups and expected patterns of adherence.

Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa Rican children with otitis media before and after the introduction of the 7-valent pneumococcal conjugate vaccine in the National Immunization Program: acute otitis media microbiology in Costa Rican children.

PubMed

Abdelnour, Arturo; Arguedas, Adriano; Dagan, Ron; Soley, Carolina; Porat, Nurith; Castrejon, Maria Mercedes; Ortega-Barria, Eduardo; Colindres, Romulo; Pirçon, Jean-Yves; DeAntonio, Rodrigo; Van Dyke, Melissa K

2015-01-01

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010-2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥ 2 PCV7 doses or ≥ 1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.

Who has a clue to preventing the flu? Unravelling supply and demand effects on the take-up of influenza vaccinations.

PubMed

Maurer, Jürgen

2009-05-01

Influenza is a serious disease, especially for older people, and incomplete vaccination take-up poses a major public health challenge. On both the side of physicians and patients, there could be promising channels for increasing immunization rates, but no attempt has yet been made to empirically unravel their respective influences. Using exclusion restrictions implied by an economic model of physician-patient interactions, our study quantifies the particular effects of supply and demand on influenza immunization. On the supply side, our estimates highlight the importance of physician agency and physician quality, while a patient's education and health behaviors are key demand side factors.

Intranasal Immunization with Nontypeable Haemophilus influenzae Outer Membrane Vesicles Induces Cross-Protective Immunity in Mice

PubMed Central

Roier, Sandro; Leitner, Deborah R.; Iwashkiw, Jeremy; Schild-Prüfert, Kristina; Feldman, Mario F.; Krohne, Georg; Reidl, Joachim; Schild, Stefan

2012-01-01

Abstract Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act as a commensal and a pathogen of the respiratory tract. Especially nontypeable H. influenzae (NTHi) is a major threat to public health and is responsible for several infectious diseases in humans, such as pneumonia, sinusitis, and otitis media. Additionally, NTHi strains are highly associated with exacerbations in patients suffering from chronic obstructive pulmonary disease. Currently, there is no licensed vaccine against NTHi commercially available. Thus, this study investigated the utilization of outer membrane vesicles (OMVs) as a potential vaccine candidate against NTHi infections. We analyzed the immunogenic and protective properties of OMVs derived from various NTHi strains by means of nasopharyngeal immunization and colonization studies with BALB/c mice. The results presented herein demonstrate that an intranasal immunization with NTHi OMVs results in a robust and complex humoral and mucosal immune response. Immunoprecipitation revealed the most important immunogenic proteins, such as the heme utilization protein, protective surface antigen D15, heme binding protein A, and the outer membrane proteins P1, P2, P5 and P6. The induced immune response conferred not only protection against colonization with a homologous NTHi strain, which served as an OMV donor for the immunization mixtures, but also against a heterologous NTHi strain, whose OMVs were not part of the immunization mixtures. These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections. PMID:22880074

Priming by a novel universal influenza vaccine (Multimeric-001)-a gateway for improving immune response in the elderly population.

PubMed

Atsmon, Jacob; Caraco, Yoseph; Ziv-Sefer, Sagit; Shaikevich, Dimitry; Abramov, Ester; Volokhov, Inna; Bruzil, Svetlana; Haima, Kirsten Y; Gottlieb, Tanya; Ben-Yedidia, Tamar

2014-10-07

A new vaccine, "Multimeric-001" (M-001) has been recently developed, containing conserved, common linear influenza epitopes that activate both cellular and humoral arms of the immune system against a wide variety of influenza A and B strains. Apart from its direct action, M-001 is an attractive candidate for priming immune responses to seasonal influenza vaccine for the elderly population. The current clinical study was designed to assess M-001's standalone and priming action in participants over 65 years old. Evaluation of standalone action is based on induction of cell mediated immunity (CMI), since M-001 alone does not induce hemagglutinin inhibition (HAI) antibodies. This was a two-center, randomized, placebo-controlled study. 120 participants were randomized 1:1:1:1 into four groups to receive either two sequential non-adjuvanted or a single non-adjuvanted or a single adjuvanted intramuscular injection of 500 mcg M-001 (treatment), or one placebo (saline) injection, before receiving the trivalent inactivated influenza vaccine (TIV). Due to visual differences between placebo and treatment the study was partially blinded. HAI was evaluated at baseline and 3 weeks after standard TIV vaccination as a measure of M-001's efficacy. CMI responses were evaluated in a subset (10/group) of the participants. Participants were monitored for safety throughout the study. Overall the treatment was well-tolerated and safe, though sample sizes allowed only limited statistical analysis. M-001 priming resulted in enhanced seroconversion towards all three TIV strains, compared to priming with placebo. Significant elevation of influenza-specific CMI was observed following immunization with M-001 alone. The standalone and priming actions of M-001 were demonstrated in elderly participants despite the limitations of small population size and pre-existing HAI antibody titers in some participants. As a standalone vaccine, M-001 induced significant CMI to multiple strains and as a primer, M-001 enhanced HAI responses. Larger scale studies are warranted. NCT01419925. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epistatically Interacting Substitutions Are Enriched during Adaptive Protein Evolution

PubMed Central

Gong, Lizhi Ian; Bloom, Jesse D.

2014-01-01

Most experimental studies of epistasis in evolution have focused on adaptive changes—but adaptation accounts for only a portion of total evolutionary change. Are the patterns of epistasis during adaptation representative of evolution more broadly? We address this question by examining a pair of protein homologs, of which only one is subject to a well-defined pressure for adaptive change. Specifically, we compare the nucleoproteins from human and swine influenza. Human influenza is under continual selection to evade recognition by acquired immune memory, while swine influenza experiences less such selection due to the fact that pigs are less likely to be infected with influenza repeatedly in a lifetime. Mutations in some types of immune epitopes are therefore much more strongly adaptive to human than swine influenza—here we focus on epitopes targeted by human cytotoxic T lymphocytes. The nucleoproteins of human and swine influenza possess nearly identical numbers of such epitopes. However, mutations in these epitopes are fixed significantly more frequently in human than in swine influenza, presumably because these epitope mutations are adaptive only to human influenza. Experimentally, we find that epistatically constrained mutations are fixed only in the adaptively evolving human influenza lineage, where they occur at sites that are enriched in epitopes. Overall, our results demonstrate that epistatically interacting substitutions are enriched during adaptation, suggesting that the prevalence of epistasis is dependent on the underlying evolutionary forces at play. PMID:24811236

Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.

PubMed

Gohil, Devanshi; Kothari, Sweta; Shinde, Pramod; Meharunkar, Rhuta; Warke, Rajas; Chowdhary, Abhay; Deshmukh, Ranjana

2017-08-01

Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

Protein and modified vaccinia virus Ankara-based influenza virus nucleoprotein vaccines are differentially immunogenic in BALB/c mice.

PubMed

Altenburg, A F; Magnusson, S E; Bosman, F; Stertman, L; de Vries, R D; Rimmelzwaan, G F

2017-10-01

Because of the high variability of seasonal influenza viruses and the eminent threat of influenza viruses with pandemic potential, there is great interest in the development of vaccines that induce broadly protective immunity. Most probably, broadly protective influenza vaccines are based on conserved proteins, such as nucleoprotein (NP). NP is a vaccine target of interest as it has been shown to induce cross-reactive antibody and T cell responses. Here we tested and compared various NP-based vaccine preparations for their capacity to induce humoral and cellular immune responses to influenza virus NP. The immunogenicity of protein-based vaccine preparations with Matrix-M™ adjuvant as well as recombinant viral vaccine vector modified Vaccinia virus Ankara (MVA) expressing the influenza virus NP gene, with or without modifications that aim at optimization of CD8 + T cell responses, was addressed in BALB/c mice. Addition of Matrix-M™ adjuvant to NP wild-type protein-based vaccines significantly improved T cell responses. Furthermore, recombinant MVA expressing the influenza virus NP induced strong antibody and CD8 + T cell responses, which could not be improved further by modifications of NP to increase antigen processing and presentation. © 2017 British Society for Immunology.

Inactivated and live, attenuated influenza vaccines protect mice against influenza:Streptococcus pyogenes super-infections

PubMed Central

Chaussee, Michael S.; Sandbulte, Heather R.; Schuneman, Margaret J.; DePaula, Frank P.; Addengast, Leslie A.; Schlenker, Evelyn H.; Huber, Victor C.

2011-01-01

Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with S. pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-γ which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue to levels that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete. PMID:21440037

Identification of novel membrane-associated prostaglandin E synthase-1 (mPGES-1) inhibitors with anti-influenza activities in vitro.

PubMed

Park, Ji Hoon; Park, Eun Beul; Lee, Jae Yeol; Min, Ji-Young

2016-01-22

Influenza A virus (IAV) is a major public health concern that leads to high morbidity and mortality worldwide. Despite various vaccination programs and development of drugs targeting essential viral proteins, the emergence of drug-resistant variants has been frequently reported and the therapeutic options are limited. Because exaggerated inflammation is considered as an important factor in disease pathogenesis, immunomodulatory agents that effectively suppress cytokine responses are needed for the treatment of IAV infection. Membrane-associated prostaglandin E synthase-1 (mPGES-1) is an enzyme responsible for the production of prostaglandin E2 (PGE2) that is the best-characterized immune modulatory lipid in vitro and in vivo models of inflammation. In the present study, we tested the anti-influenza activities of mPGES-1 inhibitors, using a phenotype-based assay involving image analyses. Seven primary hits among 49 compounds targeting mPGES-1 exhibited anti-influenza activities against A/Puerto Rico/8/1934 (H1N1) in a dose-dependent manner. The most effective hit, MPO-0047, suppressed influenza-induced p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) activation. We also showed that mRNA levels of TNF-α, IL-8, CCL5/RANTES, and CXCL10/IP-10 were significantly reduced by the treatment of influenza-infected cells with MPO-0047. Exogenous PGE2 reversed the inhibitory effects of MPO-0047. Our results showed that this selective mPGES-1 inhibitor has anti-influenza effects by inhibiting PGE2 production, which suppresses the induction of pro-inflammatory genes. Taken together our data revealed that mPGES-1 inhibitor has the potential for further development as an influenza therapeutic agent. Copyright © 2015 Elsevier Inc. All rights reserved.

Cancer patients treated with sunitinib or sorafenib have sufficient antibody and cellular immune responses to warrant influenza vaccination.

PubMed

Mulder, Sasja F; Jacobs, Joannes F M; Olde Nordkamp, Michel A M; Galama, Joep M D; Desar, Ingrid M E; Torensma, Ruurd; Teerenstra, Steven; Mulders, Peter F A; Vissers, Kris C P; Punt, Cornelis J A; de Vries, I Jolanda M; van Herpen, Carla M L

2011-07-01

The tyrosine kinase inhibitors sorafenib and sunitinib have efficacy in several types of cancer. Recent studies indicate that these agents affect the immune system. The way it affects the immune response to influenza vaccination is unknown. The aim of this study was to elucidate the specific immune response to seasonal flu vaccination in cancer patients treated with sunitinib or sorafenib. Sunitinib- or sorafenib-treated cancer patients were vaccinated against seasonal influenza with an inactivated vaccine. Healthy controls and patients with metastatic renal cell cancer (mRCC) without systemic treatment (nontreated mRCC controls) were included for comparison. Antibody responses were measured at baseline, day 8, and day 22 by a standard hemagglutination inhibition assay and cellular T-cell responses at baseline and day 8 by proliferation assay and secretion of cytokines. Forty subjects were enrolled: 16 patients treated with sunitinib, 6 patients with sorafenib, 7 nontreated mRCC controls, and 11 healthy controls. All patients treated with sunitinib and sorafenib developed seroprotection rates comparable with controls. Functional T-cell reactivity was observed in all groups, except for patients treated with sorafenib who showed a decreased proliferation rate and IFN-γ/IL-2 production and increased IL-10 compared with healthy controls. We conclude that influenza vaccination should be recommended to cancer patients treated with sunitinib or sorafenib.

Intranasal influenza vaccine: Why does Canada have different recommendations from the USA on its use?

PubMed

Tam, Theresa W S

2018-02-01

Canada and the USA differ in their recommendations for the use of live attenuated influenza vaccine (LAIV). The Canadian National Advisory Committee on Immunization (NACI) continues to recommend LAIV as one of the influenza vaccines available for use in children 2 to 17 years of age. The US Advisory Committee on Immunization Practices (ACIP) made an interim recommendation against the use of LAIV for the 2016 to 2017 influenza season in response to low LAIV effectiveness observed in the USA during the 2013 to 2014 to 2015 to 2016 seasons. The recommendation has been continued for the 2017 to 2018 season. In response, NACI undertook a review of available LAIV effectiveness data in children and adolescents from Canada, the USA and a number of European countries. This commentary by Canada's Chief Public Health Officer summarizes the findings of that review and provides the rationale for Canada's current continued recommendation for LAIV use.

Microneedle and mucosal delivery of influenza vaccines

PubMed Central

Kang, Sang-Moo; Song, Jae-Min; Kim, Yeu-Chun

2017-01-01

In recent years with the threat of pandemic influenza and other public health needs, alternative vaccination methods other than intramuscular immunization have received great attention. The skin and mucosal surfaces are attractive sites probably because of both non-invasive access to the vaccine delivery and unique immunological responses. Intradermal vaccines using a microinjection system (BD Soluvia) and intranasal vaccines (FluMist) are licensed. As a new vaccination method, solid microneedles have been developed using a simple device that may be suitable for self-administration. Because coated micorneedle influenza vaccines are administered in the solid state, developing formulations maintaining the stability of influenza vaccines is an important issue to be considered. Marketable microneedle devices and clinical trials remain to be developed. Other alternative mucosal routes such as oral and intranasal delivery systems are also attractive for inducing cross protective mucosal immunity but effective non-live mucosal vaccines remain to be developed. PMID:22697052

Haemophilus influenzae type B meningitis: Is there a re-emergence? 24 years of experience in a children's hospital.

PubMed

Gentile, Angela; Martínez, Ana C; Juarez, María Del V; Lución, María F; Burgo, Candela; Della Latta, María P; Rapapor, Solana; Romanin, Viviana; Turco, Marisa

2017-06-01

Haemophilus influenzae type B (Hib) used to be the main cause of bacterial meningitis in children younger than 5 years old. Following the introduction of the Hib vaccine in the immunization schedule (1998), its incidence reduced significantly but it has increased over the last years. The objectives of this study included describing the characteristics and analyzing the epidemic curve of Haemophilus influenzae type B (Hib) meningitis by comparing the pre- and postimmunization periods. Time-series study. All patients hospitalized with Hib meningitis at Hospital de Niños "R. Gutiérrez" (January 1992-May 2016). Hospitalization rates were compared before (pre-immunization) and after (post-immunization) the introduction of the Hib vaccine. The post-immunization period was divided into three similar periods. Eighty-five patients with Hib meningitis were admitted (73.3% in the pre-immunization period). No differences were observed in relation to the clinical and sociodemographic characteristics of cases in both periods. Pre-immunization: 10.5 cases/year; postimmunization: 0.7 cases/year. As of 2014, the rate has increased. Lethality rate: 4.8% (all preimmunization). Post-immunization data (n= 15): 40% had completed their primary immunization schedule, 40% were delayed on the immunization schedule for their age. Overall reduction in the hospital rate of Hib meningitis by 89.8% (95% confidence interval: -82.79-93.96%, p < 0.001) in the post-immunization period. The analysis of the different post-immunization periods shows a decline in reduction over time. A very significant reduction in hospitalizations due to Hib meningitis was observed after the Hib vaccine was introduced; however, over the past years, the number of cases has increased although no changes have been observed in patient characteristics.

Universal influenza vaccines: Shifting to better vaccines.

PubMed

Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J

2016-06-03

Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Modeling Insights into Haemophilus influenzae Type b Disease, Transmission, and Vaccine Programs

PubMed Central

Rose, Charles E.; Cohn, Amanda; Coronado, Fatima; Clark, Thomas A.; Wenger, Jay D.; Bulkow, Lisa; Bruce, Michael G.; Messonnier, Nancy E.; Hennessy, Thomas W.

2012-01-01

In response to the 2007–2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age. PMID:22257582

Vaccine protection of turkeys against H5N1 highly pathogenic avian influenza virus with a recombinant HVT expressing the hemagglutinin gene of avian influenza

USDA-ARS?s Scientific Manuscript database

Outbreaks of H5 highly pathogenic avian influenza (HPAI) in commercial poultry are a constant threat to animal health and food supplies. While vaccination can enhance protection and reduce the spread of disease, there is considerable evidence that the level of immunity required for protection varies...

Influenza Seasonal Summary: Departments of the Navy and Defense 2015-2016

DTIC Science & Technology

2016-08-01

System (CHCS) (laboratory, pharmacy, and radiology data), inpatient admission records, ambulatory medical encounter records, and vaccination records...had a medical event report (MER). Active Duty and Recruits Influenza activity among AD and recruit Sailors and Marines were similar to overall DON...considered immune). Geographic Distribution Influenza activity among DON beneficiaries was greatest at Naval Medical Center (NMC) San Diego; other

Prior Population Immunity Reduces the Expected Impact of CTL-Inducing Vaccines for Pandemic Influenza Control

PubMed Central

Bolton, Kirsty J.; McCaw, James M.; Brown, Lorena; Jackson, David; Kedzierska, Katherine; McVernon, Jodie

2015-01-01

Vaccines that trigger an influenza-specific cytotoxic T cell (CTL) response may aid pandemic control by limiting the transmission of novel influenza A viruses (IAV). We consider interventions with hypothetical CTL-inducing vaccines in a range of epidemiologically plausible pandemic scenarios. We estimate the achievable reduction in the attack rate, and, by adopting a model linking epidemic progression to the emergence of IAV variants, the opportunity for antigenic drift. We demonstrate that CTL-inducing vaccines have limited utility for modifying population-level outcomes if influenza-specific T cells found widely in adults already suppress transmission and prove difficult to enhance. Administration of CTL-inducing vaccines that are efficacious in "influenza-experienced" and "influenza-naive" hosts can likely slow transmission sufficiently to mitigate a moderate IAV pandemic. However if neutralising cross-reactive antibody to an emerging IAV are common in influenza-experienced hosts, as for the swine-variant H3N2v, boosting CTL immunity may be ineffective at reducing population spread, indicating that CTL-inducing vaccines are best used against novel subtypes such as H7N9. Unless vaccines cannot readily suppress transmission from infected hosts with naive T cell pools, targeting influenza-naive hosts is preferable. Such strategies are of enhanced benefit if naive hosts are typically intensively mixing children and when a subset of experienced hosts have pre-existing neutralising cross-reactive antibody. We show that CTL-inducing vaccination campaigns may have greater power to suppress antigenic drift than previously suggested, and targeting adults may be the optimal strategy to achieve this when the vaccination campaign does not have the power to curtail the attack rate. Our results highlight the need to design interventions based on pre-existing cellular immunity and knowledge of the host determinants of vaccine efficacy, and provide a framework for assessing the performance requirements of high-impact CTL-inducing vaccines. PMID:25811654

Prior population immunity reduces the expected impact of CTL-inducing vaccines for pandemic influenza control.

PubMed

Bolton, Kirsty J; McCaw, James M; Brown, Lorena; Jackson, David; Kedzierska, Katherine; McVernon, Jodie

2015-01-01

Vaccines that trigger an influenza-specific cytotoxic T cell (CTL) response may aid pandemic control by limiting the transmission of novel influenza A viruses (IAV). We consider interventions with hypothetical CTL-inducing vaccines in a range of epidemiologically plausible pandemic scenarios. We estimate the achievable reduction in the attack rate, and, by adopting a model linking epidemic progression to the emergence of IAV variants, the opportunity for antigenic drift. We demonstrate that CTL-inducing vaccines have limited utility for modifying population-level outcomes if influenza-specific T cells found widely in adults already suppress transmission and prove difficult to enhance. Administration of CTL-inducing vaccines that are efficacious in "influenza-experienced" and "influenza-naive" hosts can likely slow transmission sufficiently to mitigate a moderate IAV pandemic. However if neutralising cross-reactive antibody to an emerging IAV are common in influenza-experienced hosts, as for the swine-variant H3N2v, boosting CTL immunity may be ineffective at reducing population spread, indicating that CTL-inducing vaccines are best used against novel subtypes such as H7N9. Unless vaccines cannot readily suppress transmission from infected hosts with naive T cell pools, targeting influenza-naive hosts is preferable. Such strategies are of enhanced benefit if naive hosts are typically intensively mixing children and when a subset of experienced hosts have pre-existing neutralising cross-reactive antibody. We show that CTL-inducing vaccination campaigns may have greater power to suppress antigenic drift than previously suggested, and targeting adults may be the optimal strategy to achieve this when the vaccination campaign does not have the power to curtail the attack rate. Our results highlight the need to design interventions based on pre-existing cellular immunity and knowledge of the host determinants of vaccine efficacy, and provide a framework for assessing the performance requirements of high-impact CTL-inducing vaccines.

Influenza-specific T cells from older people are enriched in the late effector subset and their presence inversely correlates with vaccine response.

PubMed

Wagar, Lisa E; Gentleman, Beth; Pircher, Hanspeter; McElhaney, Janet E; Watts, Tania H

2011-01-01

T cells specific for persistent pathogens accumulate with age and express markers of immune senescence. In contrast, much less is known about the state of T cell memory for acutely infecting pathogens. Here we examined T cell responses to influenza in human peripheral blood mononuclear cells from older (>64) and younger (<40) donors using whole virus restimulation with influenza A (A/PR8/34) ex vivo. Although most donors had pre-existing influenza reactive T cells as measured by IFNγ production, older donors had smaller populations of influenza-responsive T cells than young controls and had lost a significant proportion of their CD45RA-negative functional memory population. Despite this apparent dysfunction in a proportion of the older T cells, both old and young donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA-A2+ donors, MHC tetramer staining showed that a higher proportion of influenza-specific memory CD8 T cells from the 65+ group co-express the markers killer cell lectin-like receptor G1 (KLRG1) and CD57 compared to their younger counterparts. These markers have previously been associated with a late differentiation state or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen show signs of advanced differentiation and functional deterioration with age. There was a significant negative correlation between the frequency of KLRG1(+)CD57(+) influenza M1-specific CD8 T cells pre-vaccination and the ability to make antibodies in response to vaccination with seasonal trivalent inactivated vaccine, whereas no such trend was observed when the total CD8(+)KLRG1(+)CD57(+) population was analyzed. These results suggest that the state of the influenza-specific memory CD8 T cells may be a predictive indicator of a vaccine responsive healthy immune system in old age.

Glycans from avian influenza virus are recognized by chicken dendritic cells and are targets for the humoral immune response in chicken.

PubMed

de Geus, Eveline D; Tefsen, Boris; van Haarlem, Daphne A; van Eden, Willem; van Die, Irma; Vervelde, Lonneke

2013-12-01

To increase our understanding of the interaction between avian influenza virus and its chicken host, we identified receptors for putative avian influenza virus (AIV) glycan determinants on chicken dendritic cells. Chicken dendritic cells (DCs) were found to recognize glycan determinants containing terminal αGalNAc, Galα1-3Gal, GlcNAcβ1-4GlcNAcβ1-4GlcNAcβ (chitotriose) and Galα1-2Gal. Infection of chicken dendritic cells with either low pathogenic (LP) or highly pathogenic (HP) AIV results in elevated mRNA expression of homologs of the mouse C-type lectins DEC205 and macrophage mannose receptor (MMR), whereas expression levels of the human dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) homolog remained unchanged. Following uptake and subsequent presentation of avian influenza virus by DCs, adaptive immunity, including humoral immune responses are induced. We have investigated the antibody responses against virus glycan epitopes after avian influenza virus infection. Using glycan micro-array analysis we showed that chicken contained antibodies that predominantly recognize terminal Galα1-3Gal-R, chitotriose and Fucα1-2Galβ1-4GlcNAc-R (H-type 2). After influenza-infection, glycan array analysis showed that both levels and repertoire of glycan-recognizing antibodies decreased. However, analysis of the sera by ELISA indicated that the levels of different isotypes of anti-glycan Abs against specific glycan antigens was increased after influenza-infection, suggesting that the presentation of the glycan antigens and iso-type of the Abs are critical parameters to take into account when measuring anti-glycan Abs. This novel approach in avian influenza research may contribute to the development of a broad spectrum vaccine and improves our mechanistic understanding of innate and adaptive responses to glycans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with diabetes mellitus: with special reference to age, body mass index, and HbA1c.

PubMed

Egawa, Yumi; Ohfuji, Satoko; Fukushima, Wakaba; Yamazaki, Yuko; Morioka, Tomoaki; Emoto, Masanori; Maeda, Kazuhiro; Inaba, Masaaki; Hirota, Yoshio

2014-01-01

Subjects with diabetes mellitus are considered to be at high risk of influenza infection and influenza-associated complications. To evaluate the immunogenicity of the influenza A(H1N1)pdm09 vaccine among these subjects, we performed a prospective cohort study and measured hemagglutination inhibition antibody titers at baseline and 3 weeks after vaccination in 49 patients. No serious adverse events were reported. We were able to perform analyses for 48 patients, after excluding one patient with suspected infection. The vaccine induced a rise of about 9-fold in the mean antibody level. The sero-response proportion was 79%, and the sero-protection proportion was 73%. Patients with older age and lower body mass index tended to show lower immune response. Multivariate analysis indicated an independent negative effect of hemoglobin A1c level on the sero-protection proportion. A single A(H1N1)pdm09 vaccination achieved a sufficient level of immunity among diabetic patients, but both clinicians and patients should be aware of the potential for reductions in immune response.

Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants.

PubMed

Kawano, Masaaki; Morikawa, Katsuma; Suda, Tatsuya; Ohno, Naohito; Matsushita, Sho; Akatsuka, Toshitaka; Handa, Hiroshi; Matsui, Masanori

2014-01-05

Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A*02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A*02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. © 2013 Elsevier Inc. All rights reserved.

Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza and Streptococcus pneumoniae

PubMed Central

Shrestha, Sourya; Foxman, Betsy; Dawid, Suzanne; Aiello, Allison E.; Davis, Brian M.; Berus, Joshua; Rohani, Pejman

2013-01-01

A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with both Streptococcus pneumoniae and Staphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We explore an immune-mediated model of the viral–bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus and S. pneumoniae in the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4–6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness. PMID:23825111

Vitamin D, leptin and impact on immune response to seasonal influenza A/H1N1 vaccine in older persons

PubMed Central

Sadarangani, Sapna P.; Ovsyannikova, Inna G.; Goergen, Krista; Grill, Diane E.; Poland, Gregory A.

2016-01-01

ABSTRACT Background: Influenza-related complications are highest in the elderly. Vaccine efficacy is lower due to immunosenescence. Vitamin D's immunomodulatory role was studied in the context of vaccine response. Methods: We evaluated the effect of baseline 25-(OH) D on vaccine-induced immunological response in a cohort of 159 healthy subjects ages 50–74 in Rochester, MN, who received one dose of seasonal trivalent 2010–2011 influenza vaccine, containing A/California/H1N1- like virus. We examined correlations between 25-(OH) D, leptin, and leptin-related gene SNPs to understand the role of leptin and vitamin D's effects. Results: The median (IQR) baseline for total 25-(OH) D was 44.4 ng/mL (36.6–52.2 ng/mL). No correlation was observed with age. No correlation between 25-(OH) D levels and humoral immune outcomes existed at any timepoint. There was a weak positive correlation between 25-(OH) D levels and change (Day 75-Day 0) in influenza-specific granzyme-B response (r=0.16, p=0.04). We found significant associations between 3 SNPs in the PPARG gene and 25-(OH) D levels (rs1151996, p=0.01; rs1175540, p= 0.02; rs1175544, p=0.03). Conclusion: Several SNPs in the PPARG gene were significantly associated with baseline 25-(OH) D levels. Understanding the functional and mechanistic relationships between vitamin D and influenza vaccine-induced immunity could assist in directing new influenza vaccine design. PMID:26575832

Supplementation of Elderly Japanese Men and Women with Fucoidan from Seaweed Increases Immune Responses to Seasonal Influenza Vaccination12

PubMed Central

Negishi, Hirokuni; Mori, Mari; Mori, Hideki; Yamori, Yukio

2013-01-01

The elderly are known to have an inadequate immune response to influenza vaccine. Mekabu fucoidan (MF), a sulfated polysaccharide extracted from seaweed, was previously shown to have an immunomodulatory effect. We therefore investigated antibody production after influenza vaccination in elderly Japanese men and women with and without oral MF intake. A randomized, placebo-controlled, double-blind study was conducted with 70 volunteers >60 y of age. They were randomly assigned to 1 of 2 groups, consuming either MF (300 mg/d) or placebo for 4 wk, and then given a trivalent seasonal influenza vaccine. Serum was sampled at 5 and 20 wk after vaccination to measure the hemagglutination inhibition titer and natural killer cell activity. The MF group had higher antibody titers against all 3 strains contained in the seasonal influenza virus vaccine than the placebo group. Titers against the B/Brisbane/60/2008 (B) strain increased substantially more in the MF group than in the placebo group over the product consumption period. The immune response against B antigen met the European Union Licensure criteria regarding the geometric mean titer ratio in the MF group (2.4), but not in the placebo group (1.7). In the MF group, natural killer cell activity tended to increase from baseline 9 wk after MF intake (P = 0.08). However, in the placebo group no substantial increase was noted at 9 wk, and the activity decreased substantially from 9 to 24 wk. In the immunocompromised elderly, MF intake increased antibody production after vaccination, possibly preventing influenza epidemics. PMID:24005608

The C-Terminal Fragment of the Internal 110-Kilodalton Passenger Domain of the Hap Protein of Nontypeable Haemophilus influenzae Is a Potential Vaccine Candidate

PubMed Central

Liu, Dai-Fang; Mason, Kathryn W.; Mastri, Maria; Pazirandeh, Mehran; Cutter, David; Fink, Doran L.; St. Geme, Joseph W.; Zhu, Duzhang; Green, Bruce A.

2004-01-01

Nontypeable Haemophilus influenzae is a major causative agent of bacterial otitis media in children. H. influenzae Hap autotransporter protein is an adhesin composed of an outer membrane Hapβ region and a moiety of an extracellular internal 110-kDa passenger domain called HapS. The HapS moiety promotes adherence to human epithelial cells and extracellular matrix proteins, and it also mediates bacterial aggregation and microcolony formation. A recent work (D. L. Fink, A. Z. Buscher, B. A. Green, P. Fernsten, and J. W. St. Geme, Cell. Microbiol. 5:175-186, 2003) demonstrated that HapS adhesive activity resides within the C-terminal 311 amino acids (the cell binding domain) of the protein. In this study, we immunized mice subcutaneously with recombinant proteins corresponding to the C-terminal region of HapS from H. influenzae strains N187, P860295, and TN106 and examined the resulting immune response. Antisera against the recombinant proteins from all three strains not only recognized native HapS purified from strain P860295 but also inhibited H. influenzae Hap-mediated adherence to Chang epithelial cells. Furthermore, when mice immunized intranasally with recombinant protein plus mutant cholera toxin CT-E29H were challenged with strain TN106, they were protected against nasopharyngeal colonization. These observations demonstrate that the C-terminal region of HapS is capable of eliciting cross-reacting antibodies that reduce nasopharyngeal colonization, suggesting utility as a vaccine antigen for the prevention of nontypeable H. influenzae diseases. PMID:15557618

Maternal uptake of pertussis cocooning strategy and other pregnancy related recommended immunizations.

PubMed

Wong, C Y; Thomas, N J; Clarke, M; Boros, C; Tuckerman, J; Marshall, H S

2015-01-01

Maternal immunization is an important strategy to prevent severe morbidity and mortality in mothers and their offspring. This study aimed to identify whether new parents were following immunization recommendations prior to pregnancy, during pregnancy, and postnatally. A cross-sectional survey was conducted by a questionnaire administered antenatally to pregnant women attending a maternity hospital with a follow-up telephone interview at 8-10 weeks post-delivery. Factors associated with uptake of pertussis vaccination within the previous 5 y or postnatally and influenza vaccination during pregnancy were explored using log binomial regression models. A total of 297 pregnant women completed the questionnaire. For influenza vaccine, 20.3% were immunized during pregnancy and 3.0% postnatally. For pertussis vaccine, 13.1% were vaccinated within 5 y prior to pregnancy and 31 women received the vaccine postnatally, 16 (51.6%) received the vaccine >4 weeks after delivery. Receiving a recommendation from a healthcare provider (HCP) was an independent predictor for receipt of both pertussis (RR 2.07, p < 0.001) and influenza vaccine (RR 2.26, p = 0.001). Non-English speaking mothers were significantly less likely to have received pertussis vaccination prior to pregnancy or postnatally (RR 0.24, p = 0.011). Multiparous pregnant women were less likely to have received an influenza vaccine during their current pregnancy (p = 0.015). Uptake of pregnancy related immunization is low and likely due to poor knowledge of availability, language barriers and lack of recommendations from HCPs. Strategies to improve maternal vaccine uptake should include education about recommended vaccines for both HCPs and parents and written information in a variety of languages.

Nine μg intradermal influenza vaccine and 15 μg intramuscular influenza vaccine induce similar cellular and humoral immune responses in adults.

PubMed

Nougarede, Nolwenn; Bisceglia, Hélène; Rozières, Aurore; Goujon, Catherine; Boudet, Florence; Laurent, Philippe; Vanbervliet, Beatrice; Rodet, Karen; Hennino, Ana; Nicolas, Jean-François

2014-01-01

Intanza® 9 μg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 μg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 μg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 μg (n=38) or IM 15 μg (n=42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 μg vaccine are similar to those to the standard IM 15 μg vaccine.

Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

DTIC Science & Technology

2011-01-01

central nervous system, optic neuritis, chronic inflammatory demyelinating polyneuropathy ) 340, 341.0, 341.8, 341.9, 377.30, 377.31, 377.32, 377.34...neuropathy, polyneuropathy due to drugs or other toxic agents, critical illness polyneuropathy , other inflammatory and toxic neuropathy) 337.0, 337.9, 354.1...Popula- tions at high risk, such as those with chronic diseases, are sometimes not well represented in clinical studies; however, additional efforts

Antibody Immunity Induced by H7N9 Avian Influenza Vaccines: Evaluation Criteria, Affecting Factors, and Implications for Rational Vaccine Design

PubMed Central

Hu, Zenglei; Jiao, Xinan; Liu, Xiufan

2017-01-01

Severe H7N9 avian influenza virus (AIV) infections in humans have public health authorities around the world on high alert for the potential development of a human influenza pandemic. Currently, the newly-emerged highly pathogenic avian influenza A (H7N9) virus poses a dual challenge for public health and poultry industry. Numerous H7N9 vaccine candidates have been generated using various platforms. Immunization trials in animals and humans showed that H7N9 vaccines are apparently poorly immunogenic because they induced low hemagglutination inhibition and virus neutralizing antibody titers. However, H7N9 vaccines elicit comparable levels of total hemagglutinin (HA)-reactive IgG antibody as the seasonal influenza vaccines, suggesting H7N9 vaccines are as immunogenic as their seasonal counterparts. A large fraction of overall IgG antibody is non-neutralizing antibody and they target unrecognized epitopes outside of the traditional antigenic sites in HA. Further, the Treg epitope identified in H7 HA may at least partially contribute to regulation of antibody immunity. Here, we review the latest advances for the development of H7N9 vaccines and discuss the influence of serological criteria on evaluation of immunogenicity of H7N9 vaccines. Next, we discuss factors affecting antibody immunity induced by H7N9 vaccines, including the change in antigenic epitopes in HA and the presence of the Treg epitope. Last, we present our perspectives for the unique features of antibody immunity of H7N9 vaccines and propose some future directions to improve or modify antibody response induced by H7N9 vaccines. This perspective would provide critical implications for rational design of H7N9 vaccines for human and veterinary use. PMID:29018438

Child, Household, and Caregiver Characteristics Associated with Hospitalization for Influenza Among Children 6–59 Months of Age

PubMed Central

2014-01-01

Background: Young children are at increased risk of severe outcomes from influenza illness, including hospitalization. We conducted a case-control study to identify risk factors for influenza-associated hospitalizations among children in US Emerging Infections Program sites. Methods: Cases were children 6–59 months of age hospitalized for laboratory-confirmed influenza infections during 2005–2008. Age- and zip-code-matched controls were enrolled. Data on child, caregiver and household characteristics were collected from parents and medical records. Conditional logistic regression was used to identify independent risk factors for hospitalization. Results: We enrolled 290 (64%) of 454 eligible cases and 1089 (49%) of 2204 eligible controls. Risk for influenza hospitalization increased with maternal age <26 years [odds ratio (OR): 1.8, 95% confidence interval (CI): 1.1–2.9]; household income below the poverty threshold (OR: 2.2, 95% CI: 1.4–3.6); smoking by >50% of household members (OR: 2.9, 95% CI: 1.4–6.6); lack of household influenza vaccination (OR: 1.8, 95% CI: 1.2–2.5) and presence of chronic illnesses, including hematologic/oncologic (OR: 11.8, 95% CI: 4.5–31.0), pulmonary (OR: 2.9, 95% CI: 1.9–4.4) and neurologic (OR: 3.8, 95% CI: 1.6–9.2) conditions. Full influenza immunization decreased the risk among children 6–23 months of age (OR: 0.5, 95% CI: 0.3–0.9) but not among those 24–59 months of age (OR: 1.5, 95% CI: 0.8–3.0; P value for difference = 0.01). Conclusions: Chronic illnesses, young maternal age, poverty, household smoking and lack of household influenza vaccination increased the risk of influenza hospitalization. These characteristics may help providers to identify young children who are at greatest risk for severe outcomes from influenza illness. PMID:24642518

Influence of clinical outcome and outcome period definitions on estimates of absolute clinical and economic benefits of influenza vaccination in community dwelling elderly persons.

PubMed

Nichol, K L; Nordin, J; Mullooly, J

2006-03-06

Studies assessing the clinical and economic benefits of vaccination in the elderly have used different clinical outcomes (e.g. hospitalizations for pneumonia or influenza versus hospitalizations for respiratory and cardiovascular causes) and different outcome periods (e.g. peak versus total influenza season) on which to base estimates of clinical effectiveness and cost effectiveness. We explored the implications of these varying approaches by comparing two health economic analysis models of influenza vaccination of community-dwelling elderly persons. We developed computerized models using clinical data from 3 large US HMOs for the 1998-1999 and 1999-2000 influenza seasons. The primary health economic model used a broad definition of clinical events and outcome period and included hospitalizations for all respiratory and cardiovascular events that occurred during the entire influenza season. The alternative model used more restrictive definitions and included pneumonia or influenza hospitalizations occurring during the peak influenza season. The results of Monte Carlo simulation showed that, with the more inclusive primary model, influenza vaccination resulted in net medical care cost savings due to fewer respiratory or cardiovascular hospitalizations of Dollars 71/person vaccinated (5th-95th percentile Dollars 32-118) and net savings of Dollars 809/year of life saved (5th-95th percentile Dollars 331-1450). In contrast, the alternate model found costs of Dollars 3.50/person vaccinated (5th-95th percentile Dollars -11 to 5) and net costs of Dollars 91/year of life saved (5th-95th percentile Dollars -309 to 126). Our findings confirm that influenza vaccination of the elderly is most likely cost saving and supports policies and programs that advocate routine immunization of all persons 65 and older. They also highlight how different outcome definitions can influence the results of health economic analyses.

Financing and systems barriers to seasonal influenza vaccine delivery in community settings.

PubMed

Penfold, Robert B; Rusinak, Donna; Lieu, Tracy A; Shefer, Abigail; Messonnier, Mark; Lee, Grace M

2011-12-06

Recommendations for annual seasonal influenza vaccination have expanded to now include >300 million children and adults each year. Community settings have become increasingly important venues for influenza vaccination. We sought to identify barriers to and solutions for expanding influenza vaccination in community settings. Semi-structured telephone interviews were conducted from 01/09 to 06/10 with a range of stakeholders involved in influenza vaccination, including health plans, medical services firms, retail based clinics, pharmacies, schools, and state and local public health immunization programs. Participants (n=65) were asked about barriers and feasible solutions to influenza vaccine delivery to children and adults in community settings. Key themes were identified through iterative coding using a grounded theory approach. Stakeholders identified specific financial barriers to influenza vaccine delivery in 3 major areas: purchase and distribution, delivery, and reimbursement. Limited purchasing power, the uncertain nature of public demand, and unpredictable timing of influenza vaccine supply were important barriers to enhance delivery in community settings. Barriers to delivery included complexities in running off-site clinics, especially in school settings, the need to manage publicly vs. privately purchased vaccines separately, and state-to-state variability in requirements for credentialing, physician oversight, and reporting. Reimbursement barriers included a protracted credentialing process, the need to determine insurance eligibility at point-of-service, and lack of a billing infrastructure in off-site clinics. Opportunities to mitigate financial barriers to influenza vaccine delivery in community settings focused on coordination across providers and the role of public health as a "trusted broker" to overcome existing challenges. Financial and systems barriers hamper the optimal use of community settings to effectively deliver influenza vaccines. Public health partners at the federal, state, and local levels are well-positioned to facilitate the engagement of all stakeholders in this important and complex vaccine delivery system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Preparing for an influenza pandemic: model of an immunization clinic in an urban family practice

PubMed Central

Bourgeois, Nicole; Franke, Carolyn; O’Connor, Shirlee A.; Shaw, Holly; Hum, Susan; Dunn, Sheila

2011-01-01

Abstract Problem addressed The surge in patient demand for the H1N1 influenza vaccine during the 2009 pandemic. Objective of the program To facilitate timely delivery of the 2009 H1N1 influenza vaccine to a family practice population while preserving regular clinic function and to create a model of effective vaccination delivery for future outbreaks. Program description An academic family practice in Toronto, Ont, adopted a process-improvement approach and implemented 3 Saturday stand-alone H1N1 vaccination clinics to accommodate increased demand for the vaccine. Medical directives were developed to give nurses the authority to vaccinate patients. Consent forms with eligibility criteria and risks versus benefits sheets were provided to patients in the waiting area to make optimal use of time. The clinic with “appointment blocks” for patients had improved efficiency (ie, fewer bottlenecks from waiting area to vaccination room), which was satisfactory to both staff and patients. Conclusion During a pandemic, when patient demand for vaccination is high, such stand-alone vaccination clinics in conjunction with family practices can deliver vaccines to patients in a timely and acceptable manner while promoting continuity of care. This model requires the commitment of extra staffing resources if regular primary care delivery is to be maintained. PMID:21998244

Prophylactic Administration of Bacterially Derived Immunomodulators Improves the Outcome of Influenza Virus Infection in a Murine Model▿

PubMed Central

Norton, Elizabeth B.; Clements, John D.; Voss, Thomas G.; Cárdenas-Freytag, Lucia

2010-01-01

Prophylactic or therapeutic immunomodulation is an antigen-independent strategy that induces nonspecific immune system activation, thereby enhancing host defense to disease. In this study, we investigated the effect of prophylactic immunomodulation on the outcome of influenza virus infection using three bacterially derived immune-enhancing agents known for promoting distinct immunological profiles. BALB/c mice were treated nasally with either cholera toxin (CT), a mutant form of the CT-related Escherichia coli heat-labile enterotoxin designated LT(R192G), or CpG oligodeoxynucleotide. Mice were subsequently challenged with a lethal dose of influenza A/PR/8/34 virus 24 h after the last immunomodulation treatment and either monitored for survival or sacrificed postchallenge for viral and immunological analysis. Treatment with the three immunomodulators prevented or delayed mortality and weight loss, but only CT and LT(R192G) significantly reduced initial lung viral loads as measured by plaque assay. Analysis performed 4 days postinfection indicated that prophylactic treatments with CT, LT(R192G), or CpG resulted in significantly increased numbers of CD4 T cells, B cells, and dendritic cells and altered costimulatory marker expression in the airways of infected mice, coinciding with reduced expression of pulmonary chemokines and the appearance of inducible bronchus-associated lymphoid tissue-like structures in the lungs. Collectively, these results suggest that, despite different immunomodulatory mechanisms, CT, LT(R192G), and CpG induce an initial inflammatory process and enhance the immune response to primary influenza virus challenge while preventing potentially damaging chemokine expression. These studies provide insight into the immunological parameters and immune modulation strategies that have the potential to enhance the nonspecific host response to influenza virus infection. PMID:20053748

Pre-Existing Immunity with High Neutralizing Activity to 2009 Pandemic H1N1 Influenza Virus in Shanghai Population

PubMed Central

Chen, Zhihui; Tang, Ziwei; Xu, Qingqiang; Wang, Yue; Zhao, Ping; Qi, Zhongtian

2013-01-01

Pre-existing immunity is an important factor countering the pandemic potential of an emerging influenza virus strain. Thus, studying of pre-existing immunity to the 2009 pandemic H1N1 virus (2009 H1N1) will advance our understanding of the pathogenesis and epidemiology of this emerging pathogen. In the present study, sera were collected from 486 individuals in a hospital in Shanghai, China, before the 2009 H1N1 influenza pandemic. The serum anti-hemagglutinins (HA) antibody, hemagglutination inhibition (HI) antibody and neutralizing antibody against the 2009 H1N1 were assayed. Among this population, 84.2%, 14.61% and 26.5% subjects possessed anti-HA antibody, HI antibody and neutralizing antibody, respectively. Although neutralizing antibody only existed in those sera with detectable anti-HA antibody, there was no obvious correlation between the titers of anti-HA and neutralizing antibody. However, the titers of anti-HA and neutralizing antibody against seasonal H1N1 virus were highly correlated. In the same population, there was no correlation between titers of neutralizing antibody against 2009 H1N1 and seasonal H1N1. DNA immunization performed on mice demonstrated that antibodies to the HA of 2009 pandemic and seasonal H1N1 influenza viruses were strain-specific and had no cross-neutralizing activity. In addition, the predicted conserved epitope in the HA of 2009 H1N1 and recently circulating seasonal H1N1 virus, GLFGAIAGFIE, was not an immunologically valid B-cell epitope. The data in this report are valuable for advancing our understanding of 2009 H1N1 influenza virus infection. PMID:23527030

Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine

PubMed Central

Woodruff, Matthew C.; Heesters, Balthasar A.; Herndon, Caroline N.; Groom, Joanna R.; Thomas, Paul G.; Luster, Andrew D.; Turley, Shannon J.

2014-01-01

Dendritic cells (DCs) are well established as potent antigen-presenting cells critical to adaptive immunity. In vaccination approaches, appropriately stimulating lymph node–resident DCs (LNDCs) is highly relevant to effective immunization. Although LNDCs have been implicated in immune response, their ability to directly drive effective immunity to lymph-borne antigen remains unclear. Using an inactive influenza vaccine model and whole node imaging approaches, we observed surprising responsiveness of LNDC populations to vaccine arrival resulting in a transnodal repositioning into specific antigen collection sites within minutes after immunization. Once there, LNDCs acquired viral antigen and initiated activation of viral specific CD4+ T cells, resulting in germinal center formation and B cell memory in the absence of skin migratory DCs. Together, these results demonstrate an unexpected stimulatory role for LNDCs where they are capable of rapidly locating viral antigen, driving early activation of T cell populations, and independently establishing functional immune response. PMID:25049334

Longitudinal analysis of the peripheral B cell repertoire reveals unique effects of immunization with a new influenza virus strain.

PubMed

Cortina-Ceballos, Bernardo; Godoy-Lozano, Elizabeth Ernestina; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Sámano-Sánchez, Hugo; Aguilar-Salgado, Andrés; Gómez-Barreto, Rosa Elena; Valdovinos-Torres, Humberto; López-Martínez, Irma; Aparicio-Antonio, Rodrigo; Rodríguez, Mario H; Martínez-Barnetche, Jesús

2015-11-25

Despite the potential to produce antibodies that can neutralize different virus (heterotypic neutralization), there is no knowledge of why vaccination against influenza induces protection predominantly against the utilized viral strains (homotypic response). Identification of structural patterns of the B cell repertoire associated to heterotypic neutralization may contribute to identify relevant epitopes for a universal vaccine against influenza. Blood samples were collected from volunteers immunized with 2008/2009 trivalent inactivated vaccine (TIV), pandemic H1N1 (pdmH1N1) monovalent inactivated vaccine (MIV) and the 2014/2015 TIV. Neutralization was assessed by hemagglutination and microneutralization test. IgG V(H) amplicons derived from peripheral blood RNA from pre-immune and 7 days post vaccination were subjected to 454-Roche sequencing. Full reconstruction of the sampled repertoires was done with ImmunediveRsity. The TIV induced a predominantly homotypic neutralizing serologic response, while the 09 MIV induced a heterotypic neutralizing seroconversion in 17% of the individuals. Both the 08/09 and the 14/15 TIV were associated with a reduction in clonotypic diversity, whereas 09 MIV was the opposite. Moreover, TIV and MIV induced distinctive patterns of IGHV segment use that are consistent with B cell selection by conserved antigenic determinants shared by the pre-pandemic and the pandemic strains. However, low somatic hypermutation rates in IgG after 09 MIV immunization, but not after 08/09 and 14/15 TIV immunization were observed. Furthermore, no evidence of the original antigenic sin was found in the same individuals after vaccination with the three vaccines. Immunization with a new influenza virus strain (2009 pdmH1N1) induced unique effects in the peripheral B cell repertoire clonal structure, a stereotyped response involving distinctive IGHV segment use and low somatic hypermutation levels. These parameters were contrastingly different to those observed in response to pre-pandemic and post-pandemic vaccination, and may be the result of clonal selection of common antigenic determinants, as well as germinal center-independent responses that wane as the pandemic strain becomes seasonal. Our findings may contribute in the understanding of the structural and cellular basis required to develop a universal influenza vaccine.

Immunity to viruses: learning from successful human vaccines.

PubMed

Pulendran, Bali; Oh, Jason Z; Nakaya, Helder I; Ravindran, Rajesh; Kazmin, Dmitri A

2013-09-01

For more than a century, immunologists and vaccinologists have existed in parallel universes. Immunologists have for long reveled in using 'model antigens', such as chicken egg ovalbumin or nitrophenyl haptens, to study immune responses in model organisms such as mice. Such studies have yielded many seminal insights about the mechanisms of immune regulation, but their relevance to humans has been questioned. In another universe, vaccinologists have relied on human clinical trials to assess vaccine efficacy, but have done little to take advantage of such trials for studying the nature of immune responses to vaccination. The human model provides a nexus between these two universes, and recent studies have begun to use this model to study the molecular profile of innate and adaptive responses to vaccination. Such 'systems vaccinology' studies are beginning to provide mechanistic insights about innate and adaptive immunity in humans. Here, we present an overview of such studies, with particular examples from studies with the yellow fever and the seasonal influenza vaccines. Vaccination with the yellow fever vaccine causes a systemic acute viral infection and thus provides an attractive model to study innate and adaptive responses to a primary viral challenge. Vaccination with the live attenuated influenza vaccine causes a localized acute viral infection in mucosal tissues and induces a recall response, since most vaccinees have had prior exposure to influenza, and thus provides a unique opportunity to study innate and antigen-specific memory responses in mucosal tissues and in the blood. Vaccination with the inactivated influenza vaccine offers a model to study immune responses to an inactivated immunogen. Studies with these and other vaccines are beginning to reunite the estranged fields of immunology and vaccinology, yielding unexpected insights about mechanisms of viral immunity. Vaccines that have been proven to be of immense benefit in saving lives offer us a new fringe benefit: lessons in viral immunology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Memory CD4+ T cells: beyond “helper” functions

PubMed Central

Boonnak, Kobporn; Subbarao, Kanta

2012-01-01

In influenza virus infection, antibodies, memory CD8+ T cells, and CD4+ T cells have all been shown to mediate immune protection, but how they operate and interact with one another to mediate efficient immune responses against virus infection is not well understood. In this issue of the JCI, McKinstry et al. have identified unique functions of memory CD4+ T cells beyond providing “help” for B cell and CD8+ T cell responses during influenza virus infection. PMID:22820285