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.

Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to explore the effect of methodological quality on the economic attractiveness of vaccination strategies.

PubMed

Anonychuk, Andrea M; Tricco, Andrea C; Bauch, Chris T; Pham, Ba'; Gilca, Vladimir; Duval, Bernard; John-Baptiste, Ava; Woo, Gloria; Krahn, Murray

2008-01-01

Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios.Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature.Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs were <$US20 000 per QALY or life-year gained. Analyses evaluating vaccination in children, particularly in high incidence areas, produced the most attractive ICERs. For targeted vaccination, cost effectiveness was highly dependent on the risk of infection.Incidence, vaccine cost and discount rate were the most influential parameters in sensitivity analyses. Overall, analyses that evaluated the combined hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal costs and that came from studies of higher methodological quality tended to have more attractive cost-effectiveness ratios. Methodological quality varied across studies. Major methodological flaws included inappropriate model type, comparator, incidence estimate and inclusion/exclusion of costs.

Economic evaluations of varicella vaccination programmes: a review of the literature.

PubMed

Thiry, Nancy; Beutels, Philippe; Van Damme, Pierre; Van Doorslaer, Eddy

2003-01-01

Chickenpox infections are generally mild but due to their very high incidence among healthy children they give rise to considerable morbidity and occasional mortality. With the development of a varicella vaccine in the early 1970s and its progressive licensing in many countries, interest in the efficiency of varicella immunisation programmes grew. The objective of this review was to discuss the methodological aspects and results of published economic evaluations of varicella vaccination. From this, we attempted to make recommendations. A computerised search was carried out; 17 full economic evaluations of varicella vaccination were retrieved. The review identified the methodological divergences and similarities between the articles in four areas: study design, epidemiological data, economic data and model characteristics. We assessed to what extent the applied methods conform to general guidelines for the economic evaluation of healthcare interventions and compared the studies' results. The desirability of a universal vaccination programme depends on whose perspective is taken. Despite variability in data and model assumptions, the studies suggest that universal vaccination of infants is attractive to society because large savings occur from averted unproductive days for parents. For the healthcare payer, universal vaccination of infants does not generate savings. Vaccination of susceptible adolescents has been proposed by some authors as a viable alternative; the attractiveness of this is highly dependent on the negative predictive value of anamnestic screening. Targeted vaccination of healthcare workers and immunocompromised individuals appears relatively cost effective. Findings for other target groups are either contradictory or provide insufficient evidence for any unequivocal recommendations to be made. High sensitivity to vaccine price was reported in most studies. This review highlights that some aspects of these studies need to be further improved before final recommendations can be made. First, more transparency, completeness and compliance to general methodological guidelines are required. Second, because of the increasing severity of varicella with age, it is preferable and in some cases essential to use dynamic models for the assessment of universal vaccination strategies. Third, most studies focused on the strategy of vaccinating children only while their results depended heavily on disputable assumptions (regarding vaccine effectiveness and impact on herpes zoster). Since violation of these assumptions could have important adverse public health effects, we suggest pre-adolescent vaccination as a more secure alternative. This option deserves more attention in future analyses.

Understanding human papillomavirus vaccination intentions: comparative utility of the theory of reasoned action and the theory of planned behavior in vaccine target age women and men.

PubMed

Fisher, William A; Kohut, Taylor; Salisbury, Claire M A; Salvadori, Marina I

2013-10-01

Human papillomavirus (HPV) is an exceedingly prevalent sexually transmitted infection with serious medical, sexual, and relationship consequences. HPV vaccine protection is available but vaccine uptake is very inconsistent. This research applies two major theories of health behavior uptake, the Theory of Reasoned Action and the Theory of Planned Behavior, in an effort to understand intentions to receive HPV vaccine among vaccine target age women and men. The Theory of Reasoned Action asserts that attitudes toward HPV vaccination and perceptions of social support for HPV vaccination are the determinants of intentions to be vaccinated, whereas the Theory of Planned Behavior holds that attitudes toward vaccination, perceptions of social support for vaccination, and perceived ability to get vaccinated are the determinants of intentions to be vaccinated. Canadian university men (N=118) and women (N=146) in the HPV vaccine target age range took part in this correlational study online. Participants completed standard measures of attitudes toward HPV vaccination, perceptions of social support for vaccination, perceived ability to get vaccinated, beliefs about vaccination, and intentions to be vaccinated in the coming semester. Findings confirmed the propositions of the Theory of Reasoned Action and indicated that attitudes toward undergoing HPV vaccination and perceptions of social support for undergoing HPV vaccination contributed uniquely to the prediction of women's (R2=0.53) and men's (R2=0.44) intentions to be vaccinated in the coming semester. Clinical and public health education should focus on strengthening attitudes and perceptions of social support for HPV vaccination, and on the basic beliefs that appear to underlie attitudes and perceptions of social support for HPV vaccination, in efforts to promote HPV vaccine uptake. © 2013 International Society for Sexual Medicine.

Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

PubMed Central

Hauck, Nastasja C.; Kirpach, Josiane; Kiefer, Christina; Farinelle, Sophie; Morris, Stephen A.; Muller, Claude P.; Lu, I-Na

2018-01-01

To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH). Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants. PMID:29587397

Time trends in pediatric hospitalizations for hepatitis A in Greece (1999-2013): Assessment of the impact of universal infant immunization in 2008.

PubMed

Papaevangelou, V; Alexopoulou, Z; Hadjichristodoulou, C; Kourlamba, G; Katsioulis, A; Theodoridou, K; Spoulou, V; Theodoridou, M

2016-07-02

Hepatitis A vaccine was introduced in the Greek National Immunization Program in 2008. To estimate possible impact of the universal vaccination implementation, time trends of hospitalizations for hepatitis A at the Infectious Diseases Unit of a Tertiary Pediatric Hospital in Athens during 1999-2013 were analyzed. Hepatitis A hospitalizations were recorded from the discharge database and were expressed as frequencies and rate of annual departmental hospitalizations. Time series analysis (ARIMA) was used to explore trends and the impact of the vaccination. Moreover, changes in patient age, population group distribution and the duration of hospitalization were also examined. Hepatitis A hospitalizations rate significantly decreased between pre-vaccination (1999-2008) and post-vaccination (2009-2013) era from 50.5 to 20.8/1000 hospitalizations (p = 0.005). A 3-year periodicity and a trend of reduction on hepatitis A hospitalizations rates across years were noted. Roma children had significant higher rates of hepatitis A hospitalization, followed by immigrant children. Importantly, possibly due to preceding vaccine availability with considerable uptake in private market and unvaccinated group/pockets of children (Roma), overall vaccination effect was less apparent when compared to data from other countries that implemented universal vaccination. No significant change in patient age, population group distribution, or duration of hospitalization was observed. High risk groups such as Roma children should be targeted for vaccination to reduce future outbreaks.

Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

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

Hashem, Anwar M.; Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON

Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it couldmore » be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.« less

Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice

PubMed Central

Wang, Wenling; Li, Renqing; Deng, Yao; Lu, Ning; Chen, Hong; Meng, Xin; Wang, Wen; Wang, Xiuping; Yan, Kexia; Qi, Xiangrong; Zhang, Xiangmin; Xin, Wei; Lu, Zhenhua; Li, Xueren; Bian, Tao; Gao, Yingying; Tan, Wenjie

2015-01-01

The conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD50) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD50 and 10 LD50 and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics. PMID:25834017

Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice.

PubMed

Wang, Wenling; Li, Renqing; Deng, Yao; Lu, Ning; Chen, Hong; Meng, Xin; Wang, Wen; Wang, Xiuping; Yan, Kexia; Qi, Xiangrong; Zhang, Xiangmin; Xin, Wei; Lu, Zhenhua; Li, Xueren; Bian, Tao; Gao, Yingying; Tan, Wenjie; Ruan, Li

2015-06-01

The conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD50) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD50 and 10 LD50 and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Young Hispanic Men and Human Papillomavirus Vaccination Choices.

PubMed

Thomas, Tami L; Stephens, Dionne P; Johnson-Mallard, Versie; Higgins, Melinda

2016-03-01

This exploratory descriptive study examined perceived vulnerabilities to human papillomavirus (HPV) and the correlation to factors influencing vaccine beliefs and vaccine decision making in young Hispanic males attending a large public urban university. Only 24% of participants believed that the HPV vaccine could prevent future problems, and 53% said they would not be vaccinated. The best predictors of HPV vaccination in young Hispanic men were agreement with doctor recommendations and belief in the vaccine's efficacy. Machismo cultural norms influence young Hispanic men's HPV-related decision making, their perceptions of the vaccine, and how they attitudinally act on what little HPV information they have access to. This study provides culturally relevant information for the development of targeted health education strategies aimed at increasing HPV vaccination in young Hispanic men. © The Author(s) 2014.

Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

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

Hu, Weibin; Chen, Aizhong; Miao, Yi

Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarilymore » targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.« less

Logistics management in Universal Immunisation Programme.

PubMed

Bachani, D; Bansal, R D

1990-01-01

The review of the National Immunization Programme of India in 1989 focused attention to the issue of storage and distribution of vaccines. Cold-chain equipment such as walk-in-coolers (WICs), deep freezers, ice-lined refrigerators (ILRs), and vaccine carriers proliferated after the introduction of the universal immunization program (UIP) but the available units fell short of the official targets in 1988, especially ILRs (7500 proposed and 2876 available) and vaccine carriers (250,000 proposed and 35,500 available). Some states had over 6 months of supplies of vaccines whose management posed problems of losing potency: oral polio virus (OPV) potency was acceptable in 63% of stock in 1988. Syringes, needles, stoves, pressure-cooker sterilizers, dial thermometers, and refrigerator repair kits were in short supply especially at the primary health care (PHC) level. Only 1/3 of subcenters had sterilizers and 58% had vaccines carriers. Logistics management on the state level required provision of vaccines based on previous use and eligible population with even distribution throughout the year. On the district level WICs were needed for every district with 1.5 million inhabitants. Recording of vaccine requirement, utilization, and storage would aid target allocations and avoid wastage. On the institutional and PHC level an ILR and a transporting vehicle was needed. The number of women and children eligible for immunization had to be calculated based on real population figures. Cold-chain capacity of 30,000-40,000 vials was required for a district as well as about 500 reusable syringes and needles a year along with vaccination cards exceeding the number of women and children by 10% for recordkeeping at the PHC center.

Young Hispanic Men and Human Papillomavirus Vaccination Choices

PubMed Central

Stephens, Dionne P.; Johnson-Mallard, Versie; Higgins, Melinda

2014-01-01

This exploratory descriptive study examined perceived vulnerabilities to HPV and the correlation to factors influencing vaccine beliefs and vaccine decision-making in young Hispanics males attending a large public urban university. Only 24% of participants believed the HPV vaccine could prevent future problems, and 53% said they would not be vaccinated. The best predictors of HPV vaccination in young Hispanic men were agreement with doctor recommendations and belief in the vaccine’s efficacy. Machismo cultural norms influence young Hispanic men’s HPV-related decision making, their perceptions of the vaccine, and how they attitudinally act upon what little HPV information they have access to. This study provides culturally relevant information for the development of targeted health education strategies aimed at increasing HPV vaccination in young Hispanic men. PMID:24841473

Time trends in pediatric hospitalizations for hepatitis A in Greece (1999–2013): Assessment of the impact of universal infant immunization in 2008

PubMed Central

Papaevangelou, V.; Alexopoulou, Z.; Hadjichristodoulou, C.; Kourlamba, G.; Katsioulis, A.; Theodoridou, K.; Spoulou, V.; Theodoridou, M.

2016-01-01

ABSTRACT Hepatitis A vaccine was introduced in the Greek National Immunization Program in 2008. To estimate possible impact of the universal vaccination implementation, time trends of hospitalizations for hepatitis A at the Infectious Diseases Unit of a Tertiary Pediatric Hospital in Athens during 1999–2013 were analyzed. Hepatitis A hospitalizations were recorded from the discharge database and were expressed as frequencies and rate of annual departmental hospitalizations. Time series analysis (ARIMA) was used to explore trends and the impact of the vaccination. Moreover, changes in patient age, population group distribution and the duration of hospitalization were also examined. Hepatitis A hospitalizations rate significantly decreased between pre-vaccination (1999–2008) and post-vaccination (2009–2013) era from 50.5 to 20.8/1000 hospitalizations (p = 0.005). A 3-year periodicity and a trend of reduction on hepatitis A hospitalizations rates across years were noted. Roma children had significant higher rates of hepatitis A hospitalization, followed by immigrant children. Importantly, possibly due to preceding vaccine availability with considerable uptake in private market and unvaccinated group/pockets of children (Roma), overall vaccination effect was less apparent when compared to data from other countries that implemented universal vaccination. No significant change in patient age, population group distribution, or duration of hospitalization was observed. High risk groups such as Roma children should be targeted for vaccination to reduce future outbreaks. PMID:27141813

Perceptions and Attitudes of Patients About Adult Vaccination and Their Vaccination Status: Still a Long Way to Go?

PubMed

Ozisik, Lale; Calik Basaran, Nursel; Oz, S Gul; Sain Guven, Gulay; Durusu Tanriover, Mine

2017-06-29

BACKGROUND Immunization is one of the most effective public health measures to prevent disease, but vaccination rates in adult populations still remain below the targets. Patient and physician attitudes about vaccination are important for adult vaccination. In this study, we aimed to determine patient attitudes and perceptions about vaccination and the vaccination coverage rates of adult patients in a university hospital in Turkey. MATERIAL AND METHODS A survey was conducted between October 2014 and May 2015 at the Internal Medicine Outpatient Clinics of a university hospital. Adult patients were asked to fill out a questionnaire on their perceptions and attitudes about vaccination and their vaccination status. RESULTS We interviewed 512 patients ages 19-64 years. Eighty percent of the study population thought that adults should be vaccinated, while only 36.1% of the patients stated that vaccination was ever recommended to them in their adult life. Forty-eight percent of the patients stated that they were vaccinated at least once in their adulthood. The most commonly received vaccine was tetanus vaccine in general, while influenza vaccine was the leading vaccine among patients with chronic medical conditions. While 71.4% of the patients to whom vaccination was recommended received the vaccine, 34.9% of the patients received a vaccine without any recommendation. CONCLUSIONS Although the vaccine coverage rates among adults in this survey were low, the perceptions of patients about adult vaccination were mainly positive and of many of them positively reacted when their physician recommended a vaccine.

A decision analytic model for prevention of hepatitis B virus infection in Sub-Saharan Africa using birth-dose vaccination.

PubMed

Anderson, Sarah; Harper, Lorie M; Dionne-Odom, Jodie; Halle-Ekane, Gregory; Tita, Alan T N

2018-04-01

To compare prenatal maternal hepatitis B virus (HBV) screening and infant vaccination strategies to inform policy on HBV prevention in Sub-Saharan Africa. A decision analytic model was created using previously published data to assess the ability of three intervention strategies to prevent HBV infection by age 10 years. Strategy 1 comprised of universal vaccination with a pentavalent vaccine (HBV, diphtheria, tetanus, pertussis, and Haemophilus influenzae) at age 6 weeks. Strategy 2 comprised of universal HBV vaccine at birth plus pentavalent vaccine. Strategy 3 comprised of maternal prenatal HBV screening and targeted HBV vaccine at birth for all exposed infants plus pentavalent vaccine. The reference strategy provided neither maternal screening nor infant vaccination. Rates of HBV infection and costs were compared. The reference strategy had an HBV infection rate of 2360 per 10 000 children. The HBV infection rate for strategy 1 was 813 per 10 000 children vaccinated (1547 cases prevented). Strategies 2 and 3 prevented an additional 384 cases and 362 cases, respectively. Inclusion of HBV vaccination at birth was the preferred approach at a willingness-to-pay threshold of US$150. Including a birth-dose HBV vaccine in the standard schedule was both cost-effective and prevented additional infections. © 2018 International Federation of Gynecology and Obstetrics.

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

Non-conventional expression systems for the production of vaccine proteins and immunotherapeutic molecules

PubMed Central

Legastelois, Isabelle; Buffin, Sophie; Peubez, Isabelle; Mignon, Charlotte; Sodoyer, Régis; Werle, Bettina

2017-01-01

ABSTRACT The increasing demand for recombinant vaccine antigens or immunotherapeutic molecules calls into question the universality of current protein expression systems. Vaccine production can require relatively low amounts of expressed materials, but represents an extremely diverse category consisting of different target antigens with marked structural differences. In contrast, monoclonal antibodies, by definition share key molecular characteristics and require a production system capable of very large outputs, which drives the quest for highly efficient and cost-effective systems. In discussing expression systems, the primary assumption is that a universal production platform for vaccines and immunotherapeutics will unlikely exist. This review provides an overview of the evolution of traditional expression systems, including mammalian cells, yeast and E.coli, but also alternative systems such as other bacteria than E. coli, transgenic animals, insect cells, plants and microalgae, Tetrahymena thermophila, Leishmania tarentolae, filamentous fungi, cell free systems, and the incorporation of non-natural amino acids. PMID:27905833

Genome-based approaches to develop vaccines against bacterial pathogens.

PubMed

Serruto, Davide; Serino, Laura; Masignani, Vega; Pizza, Mariagrazia

2009-05-26

Bacterial infectious diseases remain the single most important threat to health worldwide. Although conventional vaccinology approaches were successful in conferring protection against several diseases, they failed to provide efficacious solutions against many others. The advent of whole-genome sequencing changed the way to think about vaccine development, enabling the targeting of possible vaccine candidates starting from the genomic information of a single bacterial isolate, with a process named reverse vaccinology. As the genomic era progressed, reverse vaccinology has evolved with a pan-genome approach and multi-strain genome analysis became fundamental for the design of universal vaccines. This review describes the applications of genome-based approaches in the development of new vaccines against bacterial pathogens.

The role of Human Papilloma Virus (HPV) vaccination in the prevention of anal cancer in individuals with Human Immunodeficiency Virus-1 (HIV-1) infection

PubMed Central

2013-01-01

The incidence of anal cancer is increasing in the general population and especially in high-risk groups. A total of 90% of anal cancers are caused by human papilloma virus (HPV) infection of the anal canal. Similar to cervical cancer, anal cancer progresses through a predictable series of premalignant stages before resulting in invasive cancer; this process begins with persistent HPV infection. The HPV vaccine represents a promising strategy to combat the increasing incidence of anal cancer. Human Immunodeficiency Virus (HIV) predisposes people to persistent HPV infection, dysplasia, and subsequent anal cancer. Patients infected with HIV should be targeted for vaccination against HPV. There are difficulties in targeting this population, the most notable being that the optimal age for vaccination is prior to identification with any high-risk groups. Universal vaccination against HPV represents the best strategy to achieve maximum protection against anal cancer in high-risk groups. PMID:24757517

M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

PubMed

Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

2014-07-31

Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mutant MHC class II epitopes drive therapeutic immune responses to cancer.

PubMed

Kreiter, Sebastian; Vormehr, Mathias; van de Roemer, Niels; Diken, Mustafa; Löwer, Martin; Diekmann, Jan; Boegel, Sebastian; Schrörs, Barbara; Vascotto, Fulvia; Castle, John C; Tadmor, Arbel D; Schoenberger, Stephen P; Huber, Christoph; Türeci, Özlem; Sahin, Ugur

2015-04-30

Tumour-specific mutations are ideal targets for cancer immunotherapy as they lack expression in healthy tissues and can potentially be recognized as neo-antigens by the mature T-cell repertoire. Their systematic targeting by vaccine approaches, however, has been hampered by the fact that every patient's tumour possesses a unique set of mutations ('the mutanome') that must first be identified. Recently, we proposed a personalized immunotherapy approach to target the full spectrum of a patient's individual tumour-specific mutations. Here we show in three independent murine tumour models that a considerable fraction of non-synonymous cancer mutations is immunogenic and that, unexpectedly, the majority of the immunogenic mutanome is recognized by CD4(+) T cells. Vaccination with such CD4(+) immunogenic mutations confers strong antitumour activity. Encouraged by these findings, we established a process by which mutations identified by exome sequencing could be selected as vaccine targets solely through bioinformatic prioritization on the basis of their expression levels and major histocompatibility complex (MHC) class II-binding capacity for rapid production as synthetic poly-neo-epitope messenger RNA vaccines. We show that vaccination with such polytope mRNA vaccines induces potent tumour control and complete rejection of established aggressively growing tumours in mice. Moreover, we demonstrate that CD4(+) T cell neo-epitope vaccination reshapes the tumour microenvironment and induces cytotoxic T lymphocyte responses against an independent immunodominant antigen in mice, indicating orchestration of antigen spread. Finally, we demonstrate an abundance of mutations predicted to bind to MHC class II in human cancers as well by employing the same predictive algorithm on corresponding human cancer types. Thus, the tailored immunotherapy approach introduced here may be regarded as a universally applicable blueprint for comprehensive exploitation of the substantial neo-epitope target repertoire of cancers, enabling the effective targeting of every patient's tumour with vaccines produced 'just in time'.

Vaccinating healthcare workers: Level of implementation, barriers and proposal for evidence-based policies in Turkey

PubMed Central

Tanriover, Mine Durusu; Altınel, Serdar; Unal, Serhat

2017-01-01

ABSTRACT The role of healthcare workers in life-long vaccination is very important in the means of 2 sided infection, rising patient awareness and being a role model for the patients. Numerous organizations publish guidelines for vaccination of HCWs, while healthcare facilities develop vaccination policies according to the accreditation standards. Nevertheless, vaccination rates among HCWs are far below targets. The obstacles to getting vaccinated or recommending vaccination may include rather universal factors such as the vaccine paradox, however in the case of HCWs, probably a different set of factors are included. The aims of this article are to gain an overview of vaccination strategies for HCWs, to assess the coverage rates of HCWs and make in-depth analyses of the potential barriers to vaccination and potential factors to motivate HCWs for vaccination in Turkey and to compare them with the global picture to improve implementation of policies concerning vaccination of HCWs. PMID:28059668

Need for Optimisation of Immunisation Strategies Targeting Invasive Meningococcal Disease in the Netherlands.

PubMed

Bousema, Josefien Cornelie Minthe; Ruitenberg, Joost

2015-09-13

Invasive meningococcal disease (IMD) is a severe bacterial infectious disease with high mortality and morbidity rates worldwide. In recent years, industrialised countries have implemented vaccines targeting IMD in their National Immunisation Programmes (NIPs). In 2002, the Netherlands successfully implemented a single dose of meningococcal serogroup C conjugate vaccine at the age of 14 months and performed a single catch-up for children ≤18 years of age. Since then the disease disappeared in vaccinated individuals. Furthermore, herd protection was induced, leading to a significant IMD reduction in non-vaccinated individuals. However, previous studies revealed that the current programmatic immunisation strategy was insufficient to protect the population in the foreseeable future. In addition, vaccines that provide protection against additional serogroups are now available. This paper describes to what extent the current strategy to prevent IMD in the Netherlands is still sufficient, taking into account the burden of disease and the latest scientific knowledge related to IMD and its prevention. In particular, primary MenC immunisation seems not to provide long-term protection, indicating a risk for possible recurrence of the disease. This can be combatted by implementing a MenC or MenACWY adolescent booster vaccine. Additional health benefits can be achieved by replacing the primary MenC by a MenACWY vaccine. By implementation of a recently licensed MenB vaccine for infants in the NIP, the greatest burden of disease would be targeted. This paper shows that optimisation of the immunisation strategy targeting IMD in the Netherlands should be considered and contributes to create awareness concerning prevention optimisation in other countries. © 2015 by Kerman University of Medical Sciences.

[Vaccination schedule of the Spanish association of paediatrics: recommendations 2010].

PubMed

Marès Bermúdez, J; van Esso Arbolave, D; Arístegui Fernández, J; Ruiz Contreras, J; González Hachero, J; Merino Moína, M; Barrio Corrales, F; Alvarez García, F J; Cilleruelo Ortega, M J; Ortigosa Del Castillo, L; Moreno Pérez, D

2010-06-01

The Vaccine Advisory Committee of the Spanish Association of Paediatrics updates annually, the immunization schedule, taking into account epidemiological data, as well as evidence of the effectiveness and efficiency of vaccines. This vaccination schedule includes grades of recommendation. The committee has graded as universal vaccines those that all children should receive, as recommended those with a profile of universal vaccination in childhood and which are desirable that all children receive, but that can be prioritized based on resources for its public funding and for risk groups those targeting groups of people in situations of epidemiological risk. The Committee considers as a priority to achieve a common immunization schedule. The Committee reaffirms the recommendation to include pneumococcal vaccination in the routine vaccination schedule. Vaccination against varicella in the second year of life is an effective strategy and therefore a desirable goal. Vaccination against rotavirus is recommended for all infants given the morbidity and high burden on the health care system. The Committee adheres to the recommendations of the Interterritorial Council of the National Health Care System in reference to routine vaccination against HPV for all girls aged 11 to 14 years and stresses the need to vaccinate against influenza and hepatitis A all patients with risk factors for these diseases. Finally, it stresses the need to update incomplete immunization schedules using accelerated immunization schedules. Copyright 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

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.

MicroRNA-Based Attenuation of Influenza Virus across Susceptible Hosts.

PubMed

Waring, Barbara M; Sjaastad, Louisa E; Fiege, Jessica K; Fay, Elizabeth J; Reyes, Ismarc; Moriarity, Branden; Langlois, Ryan A

2018-01-15

Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population, where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains. Therefore, inactivated vaccines are used instead of the more immunostimulatory live attenuated vaccines. MicroRNAs (miRNAs) have been used previously to generate attenuated influenza A viruses for use as a vaccine. Here, we systematically targeted individual influenza gene mRNAs using the same miRNA to determine the segment(s) that yields maximal attenuation potential. This analysis demonstrated that targeting of NP mRNA most efficiently ablates replication. We further increased the plasticity of miRNA-mediated attenuation of influenza A virus by exploiting a miRNA, miR-21, that is ubiquitously expressed across influenza-susceptible hosts. In order to construct this targeted virus, we used CRISPR/Cas9 to eliminate the universally expressed miR-21 from MDCK cells. miR-21-targeted viruses were attenuated in human, mouse, canine, and avian cells and drove protective immunity in mice. This strategy has the potential to enhance the safety of live attenuated vaccines in humans and zoonotic reservoirs. IMPORTANCE Influenza A virus circulates annually in both avian and human populations, causing significant morbidity, mortality, and economic burden. High incidence of zoonotic infections greatly increases the potential for transmission to humans, where no preexisting immunity or vaccine exists. There is a critical need for new vaccine strategies to combat emerging influenza outbreaks. MicroRNAs were used previously to attenuate influenza A viruses. We propose the development of a novel platform to produce live attenuated vaccines that are highly customizable, efficacious across a broad species range, and exhibit enhanced safety over traditional vaccination methods. This strategy exploits a microRNA that is expressed abundantly in influenza virus-susceptible hosts. By eliminating this ubiquitous microRNA from a cell line, targeted viruses that are attenuated across susceptible strains can be generated. This approach greatly increases the plasticity of the microRNA targeting approach and enhances vaccine safety. Copyright © 2018 American Society for Microbiology.

Hepatitis A and travel amongst Nova Scotia postsecondary students: evidence for a targeted vs. universal immunization strategy.

PubMed

Matheson, Katherine; Halperin, Beth; McNeil, Shelly; Langley, Joanne M; Mackinnon-Cameron, Donna; Halperin, Scott A

2010-11-29

Canadian guidelines recommend hepatitis A virus (HAV) vaccination for high-risk persons, such as travelers to HAV-endemic areas. The US CDC advocates universal immunization. To explore whether a universal strategy for HAV immunization rather than the Canadian targeted approach for travelers is justified by measuring compliance of postsecondary students with Canadian guidelines. A cross-sectional study using an electronic survey method elicited HAV risk factors, immunization history, disease status, and factors affecting immunization status from postsecondary students. Seropositivity was determined by measuring HAV antibodies in saliva from a convenience sample of survey participants within each study group. Statistical analysis used Fisher's exact test and logistic regression. We received 2279 completed surveys (10.6% response) and 235 saliva samples (58.7% response). A total of 1380 (60.6%) participants had traveled to HAV-endemic regions and 1851 (81.2%) were planning to do so within the next 5 years. Less than half who traveled to HAV-endemic areas reported a history of HAV vaccination (48.0%). HAV seropositivity rates were higher amongst those who traveled to (63.6%) or were planning to travel to (55.0%) HAV-endemic areas than those who had never traveled or had no plans to travel to such areas (17.4%). Only 8.9% of unvaccinated students were seropositive (5.3% of Canadian-born students). Amongst unvaccinated, seropositive students, there was a nonsignificant trend for higher seropositivity in those who had previously traveled to HAV-endemic areas (14.7%) than those who had not traveled abroad (4.4%), suggesting an exposure to HAV during travel. Nearly all (96.5%) unvaccinated students, who were willing to be vaccinated based on current knowledge or if their doctor recommended it, indicated a willingness to receive vaccine if it were provided free of charge. Current Canadian guidelines for HAV vaccination are not being followed within the postsecondary student population. Given high rates of travel to HAV-endemic areas in this population, a universal approach to HAV vaccination may be warranted. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cost effectiveness of a targeted age-based West Nile virus vaccination program.

PubMed

Shankar, Manjunath B; Staples, J Erin; Meltzer, Martin I; Fischer, Marc

2017-05-25

West Nile virus (WNV) is the leading cause of domestically-acquired arboviral disease in the United States. Several WNV vaccines are in various stages of development. We estimate the cost-effectiveness of WNV vaccination programs targeting groups at increased risk for severe WNV disease. We used a mathematical model to estimate costs and health outcomes of vaccination with WNV vaccine compared to no vaccination among seven cohorts, spaced at 10year intervals from ages 10 to 70years, each followed until 90-years-old. U.S. surveillance data were used to estimate WNV neuroinvasive disease incidence. Data for WNV seroprevalence, acute and long-term care costs of WNV disease patients, quality-adjusted life-years (QALYs), and vaccine characteristics were obtained from published reports. We assumed vaccine efficacy to either last lifelong or for 10years with booster doses given every 10years. There was a statistically significant difference in cost-effectiveness ratios across cohorts in both models and all outcomes assessed (Kruskal-Wallis test p<0.0001). The 60-year-cohort had a mean cost per neuroinvasive disease case prevented of $664,000 and disability averted of $1,421,000 in lifelong model and $882,000 and $1,887,000, respectively in 10-year immunity model; these costs were statistically significantly lower than costs for other cohorts (p<0.0001). Vaccinating 70-year-olds had the lowest cost per death averted in both models at around $4.7 million (95%CI $2-$8 million). Cost per disease case averted was lowest among 40- and 50-year-old cohorts and cost per QALY saved lowest among 60-year cohorts in lifelong immunity model. The models were most sensitive to disease incidence, vaccine cost, and proportion of persons developing disease among infected. Age-based WNV vaccination program targeting those at higher risk for severe disease is more cost-effective than universal vaccination. Annual variation in WNV disease incidence, QALY weights, and vaccine costs impact the cost effectiveness ratios. Published by Elsevier Ltd.

Influvac, a trivalent inactivated subunit influenza vaccine.

PubMed

Zuccotti, Gian Vincenzo; Fabiano, Valentina

2011-01-01

Influenza represents a major sanitary and socio-economic burden and vaccination is universally considered the most effective strategy for preventing the disease and its complications. Traditional influenza vaccines have been on the market since the late 1940s, with million of doses administered annually worldwide, and demonstrated a substantial efficacy and safety. The trivalent inactivated subunit vaccine has been available for more than 25 years and has been studied in healthy children, adults and the elderly and in people affected by underlying chronic medical conditions. We describe vaccine technology focusing on subunit vaccine production procedures and mode of action and provide updated information on efficacy and safety available data. A review of efficacy and safety data in healthy subjects and in high risk populations from major sponsor- and investigator-driven studies. The vaccine showed a good immunogenicity and a favorable safety profile in all target groups. In the panorama of actually available influenza vaccines, trivalent inactivated subunit vaccine represents a well-established tool for preventing flu and the associated complications.

Recombinant cancer vaccines and new vaccine targets. Interview by Jenaid Rees.

PubMed

Schlom, Jeffrey

2013-10-01

Interview by Jenaid Rees, Commissioning Editor Jeffrey Schlom obtained his PhD from Rutgers University (NJ, USA). After obtaining his PhD, he worked at Columbia University (NY, USA) before moving in 1973 to the National Cancer Institute, National Institutes of Health (MD, USA). Since then he has served as the Chief of several sections, including his present position as the Chief of the Laboratory of Tumor Immunology and Biology in the Center for Cancer Research which he has held for the past 30 years. During this period, he has worked as an Adjunct Professor at George Washington University (Washington, DC, USA), served on the Editorial Board of several journals and holds membership in a number of committees. He holds over 30 patents and patent applications in the areas of vaccines, tumor antigens and monoclonal antibodies and has received honors and awards throughout his career. Jeffrey Schlom has been involved in translational research involving the immunotherapy of a range of carcinomas and predominantly works in the areas of tumor immunology, mechanisms of tumor cell-immune cell interactions and immune mechanisms. He has recently been working on the design and characterization of recombinant vaccines for cancer therapy.

Towards a universal vaccine for avian influenza: Protective efficacy of modified Vaccinia virus Ankara and Adenovirus vaccines expressing conserved influenza antigens in chickens challenged with low pathogenic avian influenza virus

PubMed Central

Boyd, Amy C.; Ruiz-Hernandez, Raul; Peroval, Marylene Y.; Carson, Connor; Balkissoon, Devanand; Staines, Karen; Turner, Alison V.; Hill, Adrian V.S.; Gilbert, Sarah C.; Butter, Colin

2013-01-01

Current vaccines targeting surface proteins can drive antigenic variation resulting either in the emergence of more highly pathogenic viruses or of antigenically distinct viruses that escape control by vaccination and thereby persist in the host population. Influenza vaccines typically target the highly mutable surface proteins and do not provide protection against heterologous challenge. Vaccines which induce immune responses against conserved influenza epitopes may confer protection against heterologous challenge. We report here the results of vaccination with recombinant modified Vaccinia virus Ankara (MVA) and Adenovirus (Ad) expressing a fusion construct of nucleoprotein and matrix protein (NP + M1). Prime and boost vaccination regimes were trialled in different ages of chicken and were found to be safe and immunogenic. Interferon-γ (IFN-γ) ELISpot was used to assess the cellular immune response post secondary vaccination. In ovo Ad prime followed by a 4 week post hatch MVA boost was identified as the most immunogenic regime in one outbred and two inbred lines of chicken. Following vaccination, one inbred line (C15I) was challenged with low pathogenic avian influenza (LPAI) H7N7 (A/Turkey/England/1977). Birds receiving a primary vaccination with Ad-NP + M1 and a secondary vaccination with MVA-NP + M1 exhibited reduced cloacal shedding as measured by plaque assay at 7 days post infection compared with birds vaccinated with recombinant viruses containing irrelevant antigen. This preliminary indication of efficacy demonstrates proof of concept in birds; induction of T cell responses in chickens by viral vectors containing internal influenza antigens may be a productive strategy for the development of vaccines to induce heterologous protection against influenza in poultry. PMID:23200938

Pneumococcal vaccines for children: a global public health priority.

PubMed

Pittet, L F; Posfay-Barbe, K M

2012-10-01

Pneumococcal conjugated vaccines have been recommended in children for over a decade in many countries worldwide. Here we review the development of pneumococcal vaccines with a focus on the two types currently available for children and their safety record. We discuss also the effect of vaccines, including the 13-valent pneumococcal conjugate vaccine, on invasive pneumococcal diseases in children, particularly bacteraemia, pneumonia and meningitis, as well as on mucosal disease and carriage. In regions where immunization was implemented in young children, the number of invasive pneumococcal diseases decreased significantly, not only in the target age group, but also in younger and much older subjects. Challenges and future perspectives regarding the development of new 'universal' vaccines, which could bypass the current problem of serotype-specific protection in a context of serotype replacement, are also discussed. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Polyvalent Vaccines Targeting Oncogenic Driver Pathways

Cancer.gov

Mary L. (Nora) Disis, MD, is the Athena Distinguished Professor of Breast Cancer Research and Associate Dean for Translational Health Sciences in the University of Washington (UW) School of Medicine. She is a Professor of Medicine and Adjunct Professor of Pathology and Obstetrics and Gynecology at UW, and a Member of the Fred Hutchinson Cancer Research Center (FHCRC). She is also an American Cancer Society Clinical Professor and a Komen Scholar. In addition to directing work in the Tumor Vaccine Group, Dr. Disis is the Director of the Institute of Translational Health Sciences and the Director for the Center for Translational Medicine in Women’s Health at the UW. Dr. Disis is an expert in breast and ovarian cancer immunology and translational research. She is one of the pioneering investigators who discovered that HER-2/neu is a tumor antigen. Her work has led to several clinical trials which evaluate boosting immunity to HER-2/neu with cancer vaccines. Her research interest is in the discovery of new molecular immunologic targets in solid tumors for the development of vaccine and cellular therapy for the treatment and prevention of common malignancies. Dr. Disis is a member of Alpha Omega Alpha and the American Society of Clinical Investigation. She is also the Editor-in-Chief for JAMA Oncology, and is a member of several committees and task forces for both the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR). Dr. Disis received her MD from the University of Nebraska Medical School and completed a residency and chief residency in Internal Medicine at the University of Illinois in Chicago and her fellowship in oncology at UW/FHCRC.

Vaccines against malaria.

PubMed

Ouattara, Amed; Laurens, Matthew B

2015-03-15

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against 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.

The Evolution of the Meningitis Vaccine Project.

PubMed

Tiffay, Kathleen; Jodar, Luis; Kieny, Marie-Paule; Socquet, Muriel; LaForce, F Marc

2015-11-15

In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a "virtual vaccine company," and over the next decade managed a network of public-private and public-public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. The development, through a public-private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Behavioral Perceptions of Oakland University Female College Students towards Human Papillomavirus Vaccination

PubMed Central

2016-01-01

Human Papillomavirus (HPV) vaccination decreases the risk for cervical cancer. However, the uptake of HPV vaccine remains low when compared with other recommended vaccines. This study evaluates the knowledge and attitudes towards HPV infection and vaccination, and the readiness for the uptake of HPV vaccine amongst female students attending Oakland University (OU) in Michigan, United States. This is a cross-sectional study targeting a randomized sample of a 1000 female OU students using an online questionnaire. The data were statistically analyzed using SPSS software. A total of 192 female students, with the mean age of 24 years completed the survey. The majority of participants had previous sexual experience with occasional use of contraceptives (78.1%), were non-smokers (92.7%), and non-alcohol drinkers (54.2%). The participants had a mean knowledge score of 53.0% with a standard error of 2.3% translating to a moderately informed population. The majority agreed that HPV is life threatening (79%), the vaccine prevents cervical cancer (62%), and that side effects would not deter them from vaccination (63%). Although two thirds (67%) believed that, based on sexual practices in the United States, female college students in Michigan have a higher chance of contracting HPV, about 50% did not believe they themselves were at risk. Higher knowledge correlated with increased recommendation for the vaccine (correlation-factor 0.20, p = 0.005). Results suggested that the best predictor for improvement of vaccination was the awareness level and health education. This indicates a need for an educational intervention to raise awareness, increase HPV vaccine uptake, and decrease the incidence of cervical cancer. PMID:27203284

Universal fungal vaccines

PubMed Central

Hamad, Mawieh

2012-01-01

The complex nature of fungal pathogens, the intricate host-pathogen relationship and the health status of subjects in need of antifungal vaccination continue to hamper efforts to develop fungal vaccines for clinical use. That said, the rise of the universal vaccine concept is hoped to revive fungal vaccine research by expanding the pool of vaccine candidates worthy of clinical evaluation. It can do so through antigenic commonality-based screening for vaccine candidates from a wide range of pathogens and by reassessing the sizable collection of already available experimental and approved vaccines. Development of experimental vaccines protective against multiple fungal pathogens is evidence of the utility of this concept in fungal vaccine research. However, universal fungal vaccines are not without difficulties; for instance, development of vaccines with differential effectiveness is an issue that should be addressed. Additionally, rationalizing the development of universal fungal vaccines on health or economic basis could be contentious. Herein, universal fungal vaccines are discussed in terms of their potential usefulness and possible drawbacks. PMID:22922769

Intent to receive an HPV vaccine among university men and women and implications for vaccine administration.

PubMed

Jones, Melissa; Cook, Robert

2008-01-01

In 2006, the authors examined intention to receive an HPV vaccine among 340 college students. A total of 138 men and 202 women completed questionnaires. The authors measured intention by asking participants how likely they would be to accept an HPV vaccine that prevented against (1) all HPV, (2) cervical cancer but not genital warts, (3) genital warts but not cervical cancer, and (4) both genital warts and cervical cancer. Men and women reported high intent to receive an HPV vaccine, although women did so at a significantly higher rate (77.5% vs 88.6%, respectively; p < .01). Men were less willing to receive a vaccine that prevents cervical cancer alone than they were to receive one that prevents cervical cancer and genital warts (34.1% vs 77.5%, p < .001). Intent to receive the vaccine was significantly greater among participants who reported more than 5 sex partners and correctly answered 2 or 3 HPV knowledge questions. Interest varied according to sexual history, according to knowledge about HPV, and (in men) according to vaccine target.

Feasibility and efficacy of oral rabies vaccine SAG2 in endangered Ethiopian wolves.

PubMed

Sillero-Zubiri, Claudio; Marino, Jorgelina; Gordon, Christopher H; Bedin, Eric; Hussein, Alo; Regassa, Fekede; Banyard, Ashley; Fooks, Anthony R

2016-09-14

Diseases are a major cause of population declines in endangered populations of several canid species. Parenteral vaccination efforts to protect Ethiopian wolves (Canis simensis) from rabies have targeted the domestic dog reservoir, or the wolves themselves in response to confirmed outbreaks. Oral vaccination offers a more cost-efficient, safe and proactive approach to protect Ethiopian wolves and other threatened canids from rabies. Field trials of the oral vaccine Rabigen® SAG2Dog were undertaken in the Bale Mountains of southeastern Ethiopia. Four different bait types and three delivery methods were tested in twelve Ethiopian wolf packs, and the oral vaccine (using the preferred bait) was trialled in three packs. Vaccine uptake and immunization rates were measured through direct observations and in live-trapped animals through the assessment of biomarker levels and serological status. Commercial baits were never taken by wolves; goat meat baits had the highest uptake, compared to rodent and intestine baits. Targeted delivery from horseback and nocturnal delivery within a pack's territory performed favourably compared to random bait distribution. Bait uptake by non-target species was lowest during the nocturnal blind distribution. Of 21 wolves trapped after vaccination, 14 were positive for the biomarker iophenoxic acid (i.e. ingested the bait and most likely pierced the sachet with the vaccine). Of these, 86% (n=12/14) had levels considered sufficient to provide protective immunity to wildlife (⩾0.20IU/ml), and 50% (n=7/14) demonstrated antibody titres above the universally recognised threshold (⩾0.5IU/ml) -the baseline average was 0.09IU/ml (n=12 wolves). All but one of the wolves vaccinated in 2014 were alive 14months later. Our trials confirm the potential for SAG2, delivered in a goat meat bait, to effectively protect Ethiopian wolves against rabies, supporting the initiative for a more efficient and proactive approach to manage and eventually eliminate rabies in Ethiopian wolf populations. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

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.

Turning self-destructing Salmonella into a universal DNA vaccine delivery platform.

PubMed

Kong, Wei; Brovold, Matthew; Koeneman, Brian A; Clark-Curtiss, Josephine; Curtiss, Roy

2012-11-20

We previously developed a biological containment system using recombinant Salmonella Typhimurium strains that are attenuated yet capable of synthesizing protective antigens. The regulated delayed attenuation and programmed self-destructing features designed into these S. Typhimurium strains enable them to efficiently colonize host tissues and allow release of the bacterial cell contents after lysis. To turn such a recombinant attenuated Salmonella vaccine (RASV) strain into a universal DNA vaccine-delivery vehicle, our approach was to genetically modify RASV strains to display a hyperinvasive phenotype to maximize Salmonella host entry and host cell internalization, to enable Salmonella endosomal escape to release a DNA vaccine into the cytosol, and to decrease Salmonella-induced pyroptosis/apoptosis that allows the DNA vaccine time to traffic to the nucleus for efficient synthesis of encoded protective antigens. A DNA vaccine vector that encodes a domain that contributes to the arabinose-regulated lysis phenotype but has a eukaryotic promoter was constructed. The vector was then improved by insertion of multiple DNA nuclear-targeting sequences for efficient nuclear trafficking and gene expression, and by increasing nuclease resistance to protect the plasmid from host degradation. A DNA vaccine encoding influenza WSN virus HA antigen delivered by the RASV strain with the best genetic attributes induced complete protection to mice against a lethal influenza virus challenge. Adoption of these technological improvements will revolutionize means for effective delivery of DNA vaccines to stimulate mucosal, systemic, and cellular protective immunities, and lead to a paradigm shift in cost-effective control and prevention of a diversity of diseases.

Turning self-destructing Salmonella into a universal DNA vaccine delivery platform

PubMed Central

Kong, Wei; Brovold, Matthew; Koeneman, Brian A.; Clark-Curtiss, Josephine; Curtiss, Roy

2012-01-01

We previously developed a biological containment system using recombinant Salmonella Typhimurium strains that are attenuated yet capable of synthesizing protective antigens. The regulated delayed attenuation and programmed self-destructing features designed into these S. Typhimurium strains enable them to efficiently colonize host tissues and allow release of the bacterial cell contents after lysis. To turn such a recombinant attenuated Salmonella vaccine (RASV) strain into a universal DNA vaccine-delivery vehicle, our approach was to genetically modify RASV strains to display a hyperinvasive phenotype to maximize Salmonella host entry and host cell internalization, to enable Salmonella endosomal escape to release a DNA vaccine into the cytosol, and to decrease Salmonella-induced pyroptosis/apoptosis that allows the DNA vaccine time to traffic to the nucleus for efficient synthesis of encoded protective antigens. A DNA vaccine vector that encodes a domain that contributes to the arabinose-regulated lysis phenotype but has a eukaryotic promoter was constructed. The vector was then improved by insertion of multiple DNA nuclear-targeting sequences for efficient nuclear trafficking and gene expression, and by increasing nuclease resistance to protect the plasmid from host degradation. A DNA vaccine encoding influenza WSN virus HA antigen delivered by the RASV strain with the best genetic attributes induced complete protection to mice against a lethal influenza virus challenge. Adoption of these technological improvements will revolutionize means for effective delivery of DNA vaccines to stimulate mucosal, systemic, and cellular protective immunities, and lead to a paradigm shift in cost-effective control and prevention of a diversity of diseases. PMID:23129620

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.

A model to evaluate mass vaccination against pneumococcus as a countermeasure against pandemic influenza.

PubMed

Crowe, Sonya; Utley, Martin; Walker, Guy; Grove, Peter; Pagel, Christina

2011-07-12

A mathematical model has been developed for the purpose of evaluating vaccination against pneumococcus as a countermeasure against pandemic influenza. As the characteristics of a future pandemic cannot be known in advance, three distinct pandemic scenarios were considered, corresponding to a 1918-like pandemic, a 1957/1968-like pandemic and a 2009-like pandemic. Model estimates for each of these pandemic scenarios are presented for two options of vaccination programme; universal vaccination of the entire UK population and vaccination only of those people considered to be at heightened risk of developing influenza complications. We find that the benefits of each option (in terms of estimated number of deaths and hospital admissions avoided and the courses of antibiotics saved) are high in a 1918-like pandemic and very small in a 2009-like pandemic. Given that the decision regarding deployment of the counter measure would occur prior to knowledge of the flu-strain characteristics being available, we also present the weighted average of the outcomes from the three pandemic scenarios. Based on the historical occurrence of pandemics over the last 100 years, the weighted average of outcomes is an estimated 1400 deaths prevented by the universal vaccination option and 400 deaths saved by the targeted vaccination option (at a cost of approximately 400 million and 50 million courses of vaccine respectively). Finally, the longer term implications of using PPV as a countermeasure against pandemic influenza have been considered by estimating the expected number of courses of vaccine bought and the expected number of deaths and hospital admissions prevented over time under each policy. Copyright © 2011 Elsevier Ltd. All rights reserved.

In silico design of Mycobacterium tuberculosis epitope ensemble vaccines.

PubMed

Shah, Preksha; Mistry, Jaymisha; Reche, Pedro A; Gatherer, Derek; Flower, Darren R

2018-05-01

Effective control of Mycobacterium tuberculosis is a global necessity. In 2015, tuberculosis (TB) caused more deaths than HIV. Considering the increasing prevalence of multi-drug resistant forms of M. tuberculosis, the need for effective TB vaccines becomes imperative. Currently, the only licensed TB vaccine is Bacillus Calmette-Guérin (BCG). Yet, BCG has many drawbacks limiting its efficacy and applicability. We applied advanced computational procedures to derive a universal TB vaccine and one targeting East Africa. Our approach selects an optimal set of highly conserved, experimentally validated epitopes, with high projected population coverage (PPC). Through rigorous data analysis, five different potential vaccine combinations were selected each with PPC above 80% for East Africa and above 90% for the World. Two potential vaccines only contained CD8+ epitopes, while the others included both CD4+ and CD8+ epitopes. Our prime vaccine candidate was a putative seven-epitope ensemble comprising: SRGWSLIKSVRLGNA, KPRIITLTMNPALDI, AAHKGLMNIALAISA, FPAGGSTGSL, MLLAVTVSL, QSSFYSDW and KMRCGAPRY, with a 97.4% global PPC and a 92.7% East African PPC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunization of Health-Care Providers: Necessity and Public Health Policies

PubMed Central

Maltezou, Helena C.; Poland, Gregory A.

2016-01-01

Health-care providers (HCPs) are at increased risk for exposure to vaccine-preventable diseases (VPDs) in the workplace. The rationale for immunization of HCPs relies on the need to protect them and, indirectly, their patients from health-care-associated VPDs. Published evidence indicates significant immunity gaps for VPDs of HCPs globally. Deficits in knowledge and false perceptions about VPDs and vaccines are the most common barriers for vaccine uptake and may also influence communication about vaccines between HCPs and their patients. Most countries have immunization recommendations for HCPs; however, there are no universal policies and significant heterogeneity exists between countries in terms of vaccines, schedules, frame of implementation (recommendation or mandatory), and target categories of HCPs. Mandatory influenza immunization policies for HCPs have been implemented with high vaccine uptake rates. Stronger recommendations for HCP immunization and commitment at the level of the health-care facility are critical in order to achieve high vaccine coverage rates. Given the importance to health, mandatory immunization policies for VPDs that can cause serious morbidity and mortality to vulnerable patients should be considered. PMID:27490580

Regulatory Aspects of Sabin Type 2 Withdrawal From Trivalent Oral Poliovirus Vaccine: Process and Lessons Learned.

PubMed

Decina, Daniela; Fournier-Caruana, Jacqueline; Takane, Marina; Ostad Ali Dehaghi, Razieh; Sutter, Roland

2017-07-01

Withdrawal of type 2 oral poliovirus vaccine (OPV) in OPV-using countries required regulatory approval for use of inactivated poliovirus vaccine and bivalent OPV in routine immunization. Worldwide, a variety of mechanisms were used by member states, with some differences in approach observed between inactivated poliovirus vaccine and bivalent OPV. These included acceptance for use of World Health Organization (WHO) prequalified vaccines, registration and licensure pathways, participation in WHO-convened joint reviews of licensing dossiers, as well as pragmatic application of alternatively available mechanisms, when appropriate. Simple but effective tools were used to monitor progress and to record, authenticate, and share information. Essential to achievement of regulatory targets was ongoing communication with key stakeholders, including switch-country national regulatory authorities, vaccine manufacturers, partner organizations, and relevant units within WHO. Understanding of the regulatory environment gained through the OPV switch can be helpful in supporting further stages of the polio end game and other time-sensitive vaccine introduction programs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Universal varicella vaccine immunization in Japan.

PubMed

Yoshikawa, Tetsushi; Kawamura, Yoshiki; Ohashi, Masahiro

2016-04-07

In 1974, Japanese scientists developed a live attenuated varicella vaccine based on the Oka strain. The efficacy of the vaccine for the prevention of varicella has been primarily demonstrated in studies conducted in the United States following the adoption of universal immunization using the Oka strain varicella vaccine in 1996. Although the vaccine was developed by Japanese scientists, until recently, the vaccine has been administered on a voluntary basis in Japan resulting in a vaccine coverage rate of approximately 40%. Therefore, Japan initiated universal immunization using the Oka strain varicella vaccine in November 2014. Given the transition from voluntary to universal immunization in Japan, it will also be important to monitor the epidemiology of varicella and herpes zoster. The efficacy and safety of co-administration of the varicella vaccine and measles, mumps, and rubella vaccine have been demonstrated in many countries; however, there was no data from Japan. In order to adopt the practice of universal immunization using the Oka strain varicella vaccine in Japan, data demonstrating the efficacy and safety of co-administration of varicella vaccine and measles and rubella (MR) vaccine were required. Additionally, we needed to elucidate the appropriate time interval between the first and second administrations of the vaccine. It is also important to differentiate between wild type and Oka vaccine type strains in herpes zoster patient with past history of varicella vaccine. Thus, there are many factors to consider regarding the adoption of universal immunization in Japan to control varicella zoster virus (VZV) infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fighting the Flu with a Universal Vaccine | NIH MedlinePlus the Magazine

MedlinePlus

... Follow us Fighting the Flu with a Universal Vaccine Photo: iStock After a serious 2017–2018 flu ... have safely received seasonal flu vaccines. The universal vaccine should: Protect against multiple flu strains Be 75% ...

Cancer vaccines: an update with special focus on ganglioside antigens.

PubMed

Bitton, Roberto J; Guthmann, Marcel D; Gabri, Mariano R; Carnero, Ariel J L; Alonso, Daniel F; Fainboim, Leonardo; Gomez, Daniel E

2002-01-01

Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by the (CIM) from La Havana, Cuba, to developed new strategies for specific active immunotherapy. The project included two ganglioside based vaccines and one anti-idiotypic vaccine. We focused on two antigens: first GM3, an ubiquitous antigen which is over-expressed in several epithelial tumor types; and a second one, N-Glycolyl-GM3 a more molecule, not being expressed in normal tissues and recently found in several neoplastic cells, in particular breast, melanoma and neuroectodermal cancer cells. We developed two vaccines, one with each antigen, both using proteins derived from the outer membrane proteins (OMP) of Neisseria Meningitidis B, as carriers. We developed also the 1E10 vaccine; an anti-idiotype vaccine designed to mimic the N-Glycolyl-GM3 gangliosides. This monoclonal antibody is an Ab2-type-antibody which recognizes the Ab1 antibody called P3, the latter is a monoclonal antibody that specifically recognizes gangliosides as antigens. Since 1998 we initiated a clinical development program for these three compounds. Results of the phase I clinical trials proved that the three vaccines were safe and able to elicit specific antibody responses. In addition we were able to demonstrate the activation of the cellular arm of the immune response in patients treated with the GM3 vaccine. Although phase I trials are not designed to evaluate antitumor efficacy, it was encouraging to observe tumor shrinkage in some patients treated both with the GM3 and N-Glycolyl-GM3 vaccines. We have already begun a phase II program in several neoplastic diseases, with all three vaccines.

Effectiveness and acceptability of parental financial incentives and quasi-mandatory schemes for increasing uptake of vaccinations in preschool children: systematic review, qualitative study and discrete choice experiment.

PubMed

Adams, Jean; Bateman, Belinda; Becker, Frauke; Cresswell, Tricia; Flynn, Darren; McNaughton, Rebekah; Oluboyede, Yemi; Robalino, Shannon; Ternent, Laura; Sood, Benjamin Gardner; Michie, Susan; Shucksmith, Janet; Sniehotta, Falko F; Wigham, Sarah

2015-11-01

Uptake of preschool vaccinations is less than optimal. Financial incentives and quasi-mandatory policies (restricting access to child care or educational settings to fully vaccinated children) have been used to increase uptake internationally, but not in the UK. To provide evidence on the effectiveness, acceptability and economic costs and consequences of parental financial incentives and quasi-mandatory schemes for increasing the uptake of preschool vaccinations. Systematic review, qualitative study and discrete choice experiment (DCE) with questionnaire. Community, health and education settings in England. Qualitative study - parents and carers of preschool children, health and educational professionals. DCE - parents and carers of preschool children identified as 'at high risk' and 'not at high risk' of incompletely vaccinating their children. Qualitative study - focus groups and individual interviews. DCE - online questionnaire. The review included studies exploring the effectiveness, acceptability or economic costs and consequences of interventions that offered contingent rewards or penalties with real material value for preschool vaccinations, or quasi-mandatory schemes that restricted access to 'universal' services, compared with usual care or no intervention. Electronic database, reference and citation searches were conducted. Systematic review - there was insufficient evidence to conclude that the interventions considered are effective. There was some evidence that the quasi-mandatory interventions were acceptable. There was insufficient evidence to draw conclusions on economic costs and consequences. Qualitative study - there was little appetite for parental financial incentives. Quasi-mandatory schemes were more acceptable. Optimising current services was consistently preferred to the interventions proposed. DCE and questionnaire - universal parental financial incentives were preferred to quasi-mandatory interventions, which were preferred to targeted incentives. Those reporting that they would need an incentive to vaccinate their children completely required around £110. Those who did not felt that the maximum acceptable incentive was around £70. Systematic review - a number of relevant studies were excluded as they did not meet the study design inclusion criteria. Qualitative study - few partially and non-vaccinating parents were recruited. DCE and questionnaire - data were from a convenience sample. There is little current evidence on the effectiveness or economic costs and consequences of parental financial incentives and quasi-mandatory interventions for preschool vaccinations. Universal incentives are likely to be more acceptable than targeted ones. Preferences concerning incentives versus quasi-mandatory interventions may depend on the context in which these are elicited. Further evidence is required on (i) the effectiveness and optimal configuration of parental financial incentive and quasi-mandatory interventions for preschool vaccinations - if effectiveness is confirmed, further evidence is required on how to communicate this to stakeholders and the impact on acceptability; and (ii) the acceptability of parental financial incentive and quasi-mandatory interventions for preschool vaccinations to members of the population who are not parents of preschool children or relevant health professionals. Further consideration should be given to (i) incorporating reasons for non-vaccination into new interventions for promoting vaccination uptake; and (ii) how existing services can be optimised. This study is registered as PROSPERO CRD42012003192. The National Institute for Health Research Health Technology Assessment programme.

Determinants of students' willingness to accept a measles-mumps-rubella booster vaccination during a mumps outbreak: a cross-sectional study.

PubMed

Donkers, Hanna W; Hautvast, Jeannine L A; Akkermans, Reinier P; Swaan, Corien M; Ruijs, Wilhelmina L M; Hulscher, Marlies E J L

2015-06-20

Despite high vaccination coverage, a mumps outbreak that affected mainly vaccinated university students and their contacts took place in the Netherlands in the period 2009-2012. We presented university students with a hypothetical case in which we offered them a measles, mumps, and rubella (MMR) booster vaccination to control the mumps outbreak. The aim of this study was to get insight into the determinants of university students' willingness to accept this vaccination. A questionnaire containing 38 items was developed for the purpose of assessing students' willingness and the psychosocial and social demographic determinants influencing their willingness to accept an MMR booster vaccination. In addition, we explored how organisational characteristics influenced the willingness to be vaccinated. Data were collected at six Dutch universities; a total of 790 students from various faculties were invited to participate. This was a convenience sampling procedure. 687 university students participated (response rate 87.0%) and 60.4% of the participants said they would be willing accept the hypothetical MMR booster vaccination. The perceived seriousness of mumps (OR 6.1) was the most important predictor of willingness to accept vaccination. Students who expected the MMR vaccination to be effective and to prevent individual illness and who believed their own vaccination would help stop the epidemic were more likely to be willing than others. The students were more willing to accept vaccination when they perceived that the social norms of significant others and the government favoured vaccination. Organisational characteristics, such as offering vaccination cost free and offering it at the university site, increased students' willingness. During a mumps outbreak, university students were generally willing to accept a hypothetical MMR booster vaccination. Risk perception, outcome expectations, perceived social norms, and organisational characteristics should be taken into account in the planning of any vaccination campaign for university students during an outbreak of an infectious disease.

Pharmacy management of vaccines.

PubMed

Cannon, H Eric

2007-09-01

Although standard vaccines have traditionally been granted full coverage in managed care, the recent introduction of several novel vaccine products has necessitated the revision of pharmacy management strategies throughout the nation. To review pharmacy management strategies for a number of emerging vaccines, with unique plan perspectives from SelectHealth, an Intermountain Healthcare company serving approximately 500,000 members in Utah. Because several recently introduced vaccines target previously unaddressed diseases and carry higher costs than traditional vaccines, several plans have adapted a novel approach to manage vaccine coverage on an individual product basis. At SelectHealth, recently introduced vaccines for rotavirus, respiratory syncytial virus (RSV), herpes zoster, and human papillomavirus (HPV) have required special attention in terms of pharmacy management. After carefully weighing acquisition and administration costs, anticipated uptake and use, direct and indirect health care costs averted, and quality of life issues, plan leadership decided to cover many of the new vaccines (i.e., rotavirus, RSV, and herpes zoster) under a nonstandard vaccination benefit. However, because substantial cost savings and high use of the quadrivalent HPV vaccine was anticipated within SelectHealth, the plan decided to fully cover the product. Although they complicate traditional pharmacy management, novel vaccines provide clinical benefit that managed care organizations cannot ignore. One universal strategy will not suffice in managing all the different vaccines entering the market, and a tailored approach should be employed based on the individual characteristics and use of each product.

Effect of infection control strategy on knowledge, attitude and practice towards hepatitis B transmission and prevention in vulnerable populations.

PubMed

Al-Tawil, M M; El-Gohary, E E; El-Sayed, M H

2013-01-01

Health care workers (HCWs) and hematological patients needing blood/ blood product transfusion are particularly vulnerable to blood born infections (BBI) including viral hepatitis. To evaluate knowledge, attitude and practice (KAP) of these target groups regarding viral hepatitis B (HBV) transmission and its change with implementing infection control policy and procedures. An anonymous questionnaire with closed questions was used to evaluate KAP including vaccination status in 2 target groups, in Children Hospital, Ain Shams University, Cairo, Egypt: 184 nurses and 210 children and adolescents with blood diseases. One year after instituting infection control as a part of hospital procedures, the same questionnaire was reused to evaluate KAP towards HBV. Baseline knowledge regarding HBV transmission, sequelae and preventive measures, was poor in both groups. Among nurses, only 62% wore gloves on withdrawing or giving blood to patients, 43.5% routinely washed hands between patients and 37.5% reported exposure after sharp injury. Only 38% of patients and 40% of nurses received HBV vaccination. Targeted infection control policy and procedures significantly improved KAP regarding HBV in both groups. Vaccination coverage significantly increased and reached 88.7% for nurses and 72% for patients. Hospital based infection control units with established policy and procedures against BBI significantly improved KAP towards HBV including a significant increase in vaccination intake.

HPV and HPV vaccine information among a national sample of college and university websites.

PubMed

Fontenot, Holly B; Fantasia, Heidi Collins; Sutherland, Melissa A; Lee-St John, Terrence

2016-04-01

To describe the availability of human papillomavirus (HPV) and HPV vaccine information accessible to college students via official college and university websites. A review and analysis of HPV and HPV vaccination information abstracted from a national sample (n = 214) of college/university websites. Three abstractors systematically evaluated quality and quantity of vaccination, sexual health, and HPV disease information from health service webpages. The majority of colleges/universities had designated student health service webpages (n = 181). Of these, 86% provided information on vaccinations, but less than 50% mentioned HPV or the HPV vaccine specifically and only 32% provided any HPV educational information. Colleges/university webpages that provide sexual health and or general vaccination information had higher odds of providing information on HPV and HPV vaccination. Nurse practitioners who care for college-aged persons need to be cognizant of the many ways they can promote HPV vaccination. Providing accurate information about resources available at student health centers is a way to promote health on campus; the findings from this study indicate that HPV and HPV vaccine information may be lacking on many college/university websites. ©2015 American Association of Nurse Practitioners.

Impact of Hepatitis A vaccination with a two-dose schedule in Panama: Results of epidemiological surveillance and time trend analysis.

PubMed

Estripeaut, Dora; Contreras, Rodolfo; Tinajeros, Olga; Castrejón, Maria Mercedes; Shafi, Fakrudeen; Ortega-Barria, Eduardo; DeAntonio, Rodrigo

2015-06-22

In April 2007, Panama introduced Hepatitis A universal vaccination using a two-dose schedule (Havrix(®)junior; GSK Vaccines, Belgium). We assessed the impact of this hepatitis A vaccine three years after it was recommended for universal mass vaccination in Panama. Hepatitis A vaccination impact was assessed using two different approaches. The first approach used retrospective data (incidence and number of cases for all age groups), collected from the passive surveillance of the Epidemiologic Surveillance System of the Ministry of Health of hepatitis A and unspecified hepatitis before (2000-2006) and after (2008-2010) introduction of hepatitis A vaccine. The second approach was a prospective hospital-based active surveillance for hepatitis cases conducted in subjects (0-14 years) during 2009-2011 at three sentinel hospitals in Panama. Overall, the annual incidence of hepatitis A and unspecified hepatitis in 2008, 2009 and 2010 were 13.1, 7.9 and 3.7 per 100,000 subjects, lower than the baseline incidence of 51.1 per 100,000 subjects. In comparison to the mean baseline period (2000-2006), there was an 82% mean reduction in the overall hepatitis-related outcomes (hepatitis A and unspecified hepatitis) after vaccine introduction (2008-2010) in all age groups. In the hospital-based surveillance (2009-2011), of the 42 probable viral hepatitis A cases, nine cases were confirmed as acute hepatitis A (8 in 2009, 1 in 2010). Of these confirmed cases, two belonged to the targeted vaccine group (1-4 years) but were not vaccinated. Our study suggests that the introduction of two-dose hepatitis A vaccines in Panama has contributed to the reduction in the incidence of overall hepatitis-related outcomes for all age groups, suggesting herd protection. Additional monitoring is required to document a sustained long-term effect. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Police exposure to infectious agents: an audit of protective policies.

PubMed

Jessop, A B; Del Buono, F; Solomon, G; Mullen-Fortino, M; Rogers, J M

2014-10-01

As first responders, police officers may be exposed to infectious agents such as hepatitis viruses and human immunodeficiency virus. Their risk of infection by these viruses can be reduced with training, monitoring and, with some viruses, vaccination. To examine infection prevention policies and practices among police departments and determine provision of vaccination and infection prevention education programmes. A questionnaire sent to all police departments in five counties of south-eastern Pennsylvania to capture information about department size, immunization policies and practices, record keeping, infection prevention education and monitoring of exposures. Ninety-six of 168 departments responded (57%). Among these, policies requiring pre-employment physical examinations were almost universal (95%). Vaccination policies were less common with <15% requiring and 50% recommending hepatitis, tetanus or influenza vaccination for officers. Few departments took action to provide (2%) or cover the cost (21%) of vaccination. Fewer than 12% maintained vaccination records. Education about the risk of infectious agents was offered by 60% of the responding departments, but often just once at the start of employment. Fewer than half of the departments had systems to collect exposure information. Police departments have opportunities to improve policies and practices for infection prevention and control. Accurate documentation of vaccination status is essential to ensure provision of appropriate post-exposure assessment and treatment. Better reporting of exposure will improve understanding of the infection transmission risk, enhancing the ability to offer targeted education and services to officers. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cost-Effectiveness of Pertussis Vaccination During Pregnancy in the United States.

PubMed

Atkins, Katherine E; Fitzpatrick, Meagan C; Galvani, Alison P; Townsend, Jeffrey P

2016-06-15

Vaccination against pertussis has reduced the disease burden dramatically, but the most severe cases and almost all fatalities occur in infants too young to be vaccinated. Recent epidemiologic evidence suggests that targeted vaccination of mothers during pregnancy can reduce pertussis incidence in their infants. To evaluate the cost-effectiveness of antepartum maternal vaccination in the United States, we created an age-stratified transmission model, incorporating empirical data on US contact patterns and explicitly modeling parent-infant exposure. Antepartum maternal vaccination incurs costs of $114,000 (95% prediction interval: 82,000, 183,000) per quality-adjusted life-year, in comparison with the strategy of no adult vaccination, and is cost-effective in the United States according to World Health Organization criteria. By contrast, vaccinating a second parent is not cost-effective, and vaccination of either parent postpartum is strongly dominated by antepartum maternal vaccination. Nonetheless, postpartum vaccination of mothers who were not vaccinated antepartum improves upon the current recommendation of untargeted adult vaccination. Additionally, the temporary direct protection of the infant due to maternal antibody transfer has efficacy for infants comparable to that conferred to toddlers by the full primary vaccination series. Efficient protection against pertussis for infants begins before birth. We highly recommend antepartum vaccination for as many US mothers as possible. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Uptake and impact of a new live attenuated influenza vaccine programme in England: early results of a pilot in primary school-age children, 2013/14 influenza season.

PubMed

Pebody, R G; Green, H K; Andrews, N; Zhao, H; Boddington, N; Bawa, Z; Durnall, H; Singh, N; Sunderland, A; Letley, L; Ellis, J; Elliot, A J; Donati, M; Smith, G E; de Lusignan, S; Zambon, M

2014-06-05

As part of the introduction and roll-out of a universal childhood live-attenuated influenza vaccination programme, 4–11 year-olds were vaccinated in seven pilot areas in England in the 2013/14 influenza season. This paper presents the uptake and impact of the programme for a range of disease indicators. End-of-season uptake was defined as the number of children in the target population who received at least one dose of influenza vaccine. Between week 40 2013 and week 15 2014, cumulative disease incidence per 100,000 population (general practitioner consultations for influenza-like illness and laboratory-confirmed influenza hospitalisations), cumulative influenza swab positivity in primary and secondary care and cumulative proportion of emergency department respiratory attendances were calculated. Indicators were compared overall and by age group between pilot and non-pilot areas. Direct impact was defined as reduction in cumulative incidence based on residence in pilot relative to non-pilot areas in 4–11 year-olds. Indirect impact was reduction between pilot and non-pilot areas in <4 year-olds and >11 year-olds. Overall vaccine uptake of 52.5% (104,792/199,475) was achieved. Although influenza activity was low, a consistent, though not statistically significant, decrease in cumulative disease incidence and influenza positivity across different indicators was seen in pilot relative to non-pilot areas in both targeted and non-targeted age groups, except in older age groups, where no difference was observed for secondary care indicators.

Factors Associated with Medicaid Providers Recommendation of the HPV Vaccine to Low-Income Adolescent Girls

PubMed Central

Bynum, Shalanda A.; Staras, Stephanie A. S.; Malo, Teri L.; Giuliano, Anna R.; Shenkman, Elizabeth; Vadaparampil, Susan T.

2013-01-01

Background HPV vaccination in the US remains a public health challenge with vaccine rates of 50%. Although health care providers can facilitate HPV vaccination, several factors may impede their ability to universally recommend the vaccine. To maximize the potential of HPV vaccines, it is important to understand challenges providers face in the clinical environment. Purpose The study sought to identify factors associated with recommendation of the HPV vaccine for low-income adolescents in the early (9–10), target (11–12), early adolescent catch-up (13–14), and late adolescent catch-up (15–17) vaccination groups. Methods Surveys were mailed from October 2009-April 2010 to a random sample of Florida-based physicians serving Medicaid-enrolled adolescents. Data were analyzed in 2013. Results Among early adolescents, discomfort discussing sexually transmitted infections (STIs) with teens (odds ratio [OR]=1.75), difficulty ensuring vaccine completion (OR=0.73), and discomfort discussing STIs with parents (OR=0.44) were associated with recommendation. For target adolescents, discomfort discussing STIs with teens (OR=2.45), time constraints (OR=0.70), vaccine efficacy concerns (OR=0.65), discomfort discussing STIs with parents (OR=0.33), obstetrics/gynecology (OR=0.25) and family medicine (OR=0.24) specialty, and non-Hispanic Black patient (OR=0.15) were associated with recommendation. In early catch-up adolescents, concerns that teens will practice riskier behaviors (OR=0.57), discomfort discussing STIs with parents (OR=0.47), and family medicine specialty (OR=0.20) were associated with recommendation. For late catch-up adolescents, family medicine specialty (OR=0.13) was associated with recommendation. Conclusion Modifiable factors that impede or influence provider recommendations of HPV vaccines can be addressed through intervention. Overall, findings suggest that efforts should focus on sexuality communication and family medicine specialty. PMID:24064282

Increasing Childhood Influenza Vaccination

PubMed Central

Nowalk, Mary Patricia; Lin, Chyongchiou J.; Hannibal, Kristin; Reis, Evelyn C.; Gallik, Gregory; Moehling, Krissy K.; Huang, Hsin-Hui; Allred, Norma J.; Wolfson, David H.; Zimmerman, Richard K.

2014-01-01

Background Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. Purpose To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. Methods In 2011–2012, 20 primary care practices treating children were randomly assigned to Intervention and Control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. Results The average vaccination differences from pre-intervention to the intervention year were significantly larger in the Intervention arm (n=10 practices) than the Control arm (n=10 practices), for children aged 2–8 years (10.2 percentage points (pct pts) Intervention vs 3.6 pct pts Control) and 9–18 years (11.1 pct pts Intervention vs 4.3 pct pts Control, p<0.05), for non-white children (16.7 pct pts Intervention vs 4.6 pct pts Control, p<0.001), and overall (9.9 pct pts Intervention vs 4.2 pct pts Control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race and intervention, the likelihood of vaccination increased with younger age group (6–23 months), white race, commercial insurance, the practice’s pre-intervention vaccination rate, and being in the Intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9–18 years. Conclusions A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza vaccination uptake across age and racial groups without targeting specific groups, especially in practices with large percentages of minority children. PMID:25113138

Footrot vaccines and vaccination.

PubMed

Dhungyel, Om; Hunter, James; Whittington, Richard

2014-05-30

Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of acquired immunity. Copyright © 2014 Elsevier Ltd. 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

Planning influenza vaccination programs: a cost benefit model

PubMed Central

2012-01-01

Background Although annual influenza vaccination could decrease the significant economic and humanistic burden of influenza in the United States, immunization rates are below recommended levels, and concerns remain whether immunization programs can be cost beneficial. The research objective was to compare cost benefit of various immunization strategies from employer, employee, and societal perspectives. Methods An actuarial model was developed based on the published literature to estimate the costs and benefits of influenza immunization programs. Useful features of the model included customization by population age and risk-level, potential pandemic risk, and projection year. Various immunization strategies were modelled for an average U.S. population of 15,000 persons vaccinated in pharmacies or doctor’s office during the 2011/12 season. The primary outcome measure reported net cost savings per vaccinated (PV) from the perspective of various stakeholders. Results Given a typical U.S. population, an influenza immunization program will be cost beneficial for employers when more than 37% of individuals receive vaccine in non-traditional settings such as pharmacies. The baseline scenario, where 50% of persons would be vaccinated in non-traditional settings, estimated net savings of $6 PV. Programs that limited to pharmacy setting ($31 PV) or targeted persons with high-risk comorbidities ($83 PV) or seniors ($107 PV) were found to increase cost benefit. Sensitivity analysis confirmed the scenario-based findings. Conclusions Both universal and targeted vaccination programs can be cost beneficial. Proper planning with cost models can help employers and policy makers develop strategies to improve the impact of immunization programs. PMID:22835081

Acceptability of Parental Financial Incentives and Quasi-Mandatory Interventions for Preschool Vaccinations: Triangulation of Findings from Three Linked Studies.

PubMed

Adams, Jean; McNaughton, Rebekah J; Wigham, Sarah; Flynn, Darren; Ternent, Laura; Shucksmith, Janet

2016-01-01

Childhood vaccinations are a core component of public health programmes globally. Recent measles outbreaks in the UK and USA have prompted debates about new ways to increase uptake of childhood vaccinations. Parental financial incentives and quasi-mandatory interventions (e.g. restricting entry to educational settings to fully vaccinated children) have been successfully used to increase uptake of childhood vaccinations in developing countries, but there is limited evidence of effectiveness in developed countries. Even if confirmed to be effective, widespread implementation of these interventions is dependent on acceptability to parents, professionals and other stakeholders. We conducted a systematic review (n = 11 studies included), a qualitative study with parents (n = 91) and relevant professionals (n = 24), and an on-line survey with embedded discrete choice experiment with parents (n = 521) exploring acceptability of parental financial incentives and quasi-mandatory interventions for preschool vaccinations. Here we use Triangulation Protocol to synthesise findings from the three studies. There was a consistent recognition that incentives and quasi-mandatory interventions could be effective, particularly in more disadvantaged groups. Universal incentives were consistently preferred to targeted ones, but relative preferences for quasi-mandatory interventions and universal incentives varied between studies. The qualitative work revealed a consistent belief that financial incentives were not considered an appropriate motivation for vaccinating children. The costs of financial incentive interventions appeared particularly salient and there were consistent concerns in the qualitative work that incentives did not represent the best use of resources for promoting preschool vaccinations. Various suggestions for improving delivery of the current UK vaccination programme as an alternative to incentives and quasi-mandates were made. Parental financial incentives and quasi-mandatory interventions for increasing uptake of preschool vaccinations do not currently attract widespread enthusiastic support in the UK; but some potential benefits of these approaches are recognised.

Acceptability of Parental Financial Incentives and Quasi-Mandatory Interventions for Preschool Vaccinations: Triangulation of Findings from Three Linked Studies

PubMed Central

McNaughton, Rebekah J.; Wigham, Sarah; Flynn, Darren; Ternent, Laura; Shucksmith, Janet

2016-01-01

Background Childhood vaccinations are a core component of public health programmes globally. Recent measles outbreaks in the UK and USA have prompted debates about new ways to increase uptake of childhood vaccinations. Parental financial incentives and quasi-mandatory interventions (e.g. restricting entry to educational settings to fully vaccinated children) have been successfully used to increase uptake of childhood vaccinations in developing countries, but there is limited evidence of effectiveness in developed countries. Even if confirmed to be effective, widespread implementation of these interventions is dependent on acceptability to parents, professionals and other stakeholders. Methods We conducted a systematic review (n = 11 studies included), a qualitative study with parents (n = 91) and relevant professionals (n = 24), and an on-line survey with embedded discrete choice experiment with parents (n = 521) exploring acceptability of parental financial incentives and quasi-mandatory interventions for preschool vaccinations. Here we use Triangulation Protocol to synthesise findings from the three studies. Results There was a consistent recognition that incentives and quasi-mandatory interventions could be effective, particularly in more disadvantaged groups. Universal incentives were consistently preferred to targeted ones, but relative preferences for quasi-mandatory interventions and universal incentives varied between studies. The qualitative work revealed a consistent belief that financial incentives were not considered an appropriate motivation for vaccinating children. The costs of financial incentive interventions appeared particularly salient and there were consistent concerns in the qualitative work that incentives did not represent the best use of resources for promoting preschool vaccinations. Various suggestions for improving delivery of the current UK vaccination programme as an alternative to incentives and quasi-mandates were made. Conclusions Parental financial incentives and quasi-mandatory interventions for increasing uptake of preschool vaccinations do not currently attract widespread enthusiastic support in the UK; but some potential benefits of these approaches are recognised. PMID:27253196

A brief history of vaccines & vaccination in India.

PubMed

Lahariya, Chandrakant

2014-04-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

A brief history of vaccines & vaccination in India

PubMed Central

Lahariya, Chandrakant

2014-01-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts. PMID:24927336

Improving polio vaccination coverage in Nigeria through the use of geographic information system technology.

PubMed

Barau, Inuwa; Zubairu, Mahmud; Mwanza, Michael N; Seaman, Vincent Y

2014-11-01

Historically, microplanning for polio vaccination campaigns in Nigeria relied on inaccurate and incomplete hand-drawn maps, resulting in the exclusion of entire settlements and missed children. The goal of this work was to create accurate, coordinate-based maps for 8 polio-endemic states in northern Nigeria to improve microplanning and support tracking of vaccination teams, thereby enhancing coverage, supervision, and accountability. Settlement features were identified in the target states, using high-resolution satellite imagery. Field teams collected names and geocoordinates for each settlement feature, with the help of local guides. Global position system (GPS) tracking of vaccination teams was conducted in selected areas and daily feedback provided to supervisors. Geographic information system (GIS)-based maps were created for 2238 wards in the 8 target states. The resulting microplans included all settlements and more-efficient team assignments, owing to the improved spatial reference. GPS tracking was conducted in 111 high-risk local government areas, resulting in improved team performance and the identification of missed/poorly covered settlements. Accurate and complete maps are a necessary part of an effective polio microplan, and tracking vaccinators gives supervisors a tool to ensure that all settlements are visited. © 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.

Enhancing transit polio vaccination in collaboration with targeted stakeholders in Kaduna State, Nigeria: Lessons learnt: 2014-2015.

PubMed

Musa, Audu; Abba, Bashir; Ningi, Adamu M I; Gali, Emanuel; Bawa, Samuel; Manneh, Fadninding; Mkanda, Pascal; Banda, Richard; Yehuluashet, Yared G; Tegegne, Sisay G; Umeh, Gregory; Nsubuga, Peter; Etsano, Andrew; Shuaib, Faisal; Mohammed, Ado; Vaz, Rui G

2016-10-10

In Kaduna State of Nigeria, the high influx of people from neighboring states with eligible children for polio vaccination represents a significant proportion of the target population. Many of these children are often missed by the vaccination team. The purpose of the study was to determine the contribution of targeted stakeholders in transit polio vaccination. We used the trends of vaccinated children at transit points, motor parks and markets, well as total children vaccinated by transit teams in Chikun, Igabi and Sabon Gari Local Government Areas (LGAs) of Kaduna State, Nigeria, four rounds before and after the introduction of transit polio vaccination with targeted stakeholders in Kaduna State. A total of 87,502 under-5 children were vaccinated by the various transit teams in the three LGAs, which accounted for 3.2% of the total 2,781,162 children vaccinated by the three LGAs. For transit point vaccination, the number of vaccinated children increased from 1026 to 19,289 (302%), while motor park vaccination increased from 1289 to 4106 (318%) and market vaccination increased from 10,488 to 14,511 (138%), four rounds after the introduction of transit polio vaccination with targeted stakeholders. Engagement of targeted stakeholders significantly enhanced transit polio vaccination in Kaduna State, Nigeria. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Too late to vaccinate? The incremental benefits and cost-effectiveness of a delayed catch-up program using the 4-valent human papillomavirus vaccine in Norway.

PubMed

Burger, Emily A; Sy, Stephen; Nygård, Mari; Kristiansen, Ivar S; Kim, Jane J

2015-01-15

Human papillomavirus (HPV) vaccines are ideally administered before HPV exposure; therefore, catch-up programs for girls past adolescence have not been readily funded. We evaluated the benefits and cost-effectiveness of a delayed, 1-year female catch-up vaccination program in Norway. We calibrated a dynamic HPV transmission model to Norwegian data and projected the costs and benefits associated with 8 HPV-related conditions while varying the upper vaccination age limit to 20, 22, 24, or 26 years. We explored the impact of vaccine protection in women with prior vaccine-targeted HPV infections, vaccine cost, coverage, and natural- and vaccine-induced immunity. The incremental benefits and cost-effectiveness decreased as the upper age limit for catch-up increased. Assuming a vaccine cost of $150/dose, vaccination up to age 20 years remained below Norway's willingness-to-pay threshold (approximately $83 000/quality-adjusted life year gained); extension to age 22 years was cost-effective at a lower cost per dose ($50-$75). At high levels of vaccine protection in women with prior HPV exposure, vaccinating up to age 26 years was cost-effective. Results were stable with lower coverage. HPV vaccination catch-up programs, 5 years after routine implementation, may be warranted; however, even at low vaccine cost per dose, the cost-effectiveness of vaccinating beyond age 22 years remains uncertain. © 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.

Potential impact of spatially targeted adult tuberculosis vaccine in Gujarat, India

PubMed Central

Chatterjee, Susmita; Rao, Krishna D.; Dowdy, David W.

2016-01-01

Some of the most promising vaccines in the pipeline for tuberculosis (TB) target adolescents and adults. Unlike for childhood vaccines, high-coverage population-wide vaccination is significantly more challenging for adult vaccines. Here, we aimed to estimate the impact of vaccine delivery strategies that were targeted to high-incidence geographical ‘hotspots’ compared with randomly allocated vaccination. We developed a spatially explicit mathematical model of TB transmission that distinguished these hotspots from the general population. We evaluated the impact of targeted and untargeted vaccine delivery strategies in India—a country that bears more than 25% of global TB burden, and may be a potential early adopter of the vaccine. We collected TB notification data and conducted a demonstration study in the state of Gujarat to validate our estimates of heterogeneity in TB incidence. We then projected the impact of randomly vaccinating 8% of adults in a single mass campaign to a spatially targeted vaccination preferentially delivered to 80% of adults in the hotspots, with both strategies augmented by continuous adolescent vaccination. In consultation with vaccine developers, we considered a vaccine efficacy of 60%, and evaluated the population-level impact after 10 years of vaccination. Spatial heterogeneity in TB notification (per 100 000/year) was modest in Gujarat: 190 in the hotspots versus 125 in the remaining population. At this level of heterogeneity, the spatially targeted vaccination was projected to reduce TB incidence by 28% after 10 years, compared with a 24% reduction projected to achieve via untargeted vaccination—a 1.17-fold augmentation in the impact of vaccination by spatially targeting. The degree of the augmentation was robust to reasonable variation in natural history assumptions, but depended strongly on the extent of spatial heterogeneity and mixing between the hotspot and general population. Identifying high-incidence hotspots and quantifying spatial mixing patterns are critical to accurate estimation of the value of targeted intervention strategies. PMID:27009179

Determinants of HPV vaccination intentions among Dutch girls and their mothers: a cross-sectional study

PubMed Central

2013-01-01

Background The Dutch government recently added universal Human Papilloma Virus (HPV) vaccination for 12-year-old girls to the existing national immunization program. The participation rate for the initial catch-up campaign for girls aged 13 to 16 years in 2009 was lower (47%) than expected (70%). To inform future HPV information campaigns, this paper examines the social and psychological determinants of the HPV vaccination intentions of girls aged 13 to 16 years and their mothers who were targeted by the Dutch catch-up campaign of 2009. Methods A random sample of girls and their mothers was chosen from the Dutch vaccination register and received a letter inviting them to participate (n = 5,998 mothers and daughters). In addition, a random sample was recruited via an online panel by a marketing research company (n = 650 mothers; n = 350 daughters). Both groups were asked to complete a web-based questionnaire with questions on social demographic characteristics, social-psychological factors and HPV vaccination intention. Backward linear regression analyses were conducted to examine which social-psychological factors were most dominantly associated with vaccination intention. Results Data from 952 mothers (14%) and 642 daughters (10%) were available for the intended analyses. The contribution of social demographic variables to the explained variance of HPV vaccination intention was small but significant for mothers (ΔR2 = .01; p = .007), but not significant for daughters (ΔR2 = .02; p = .17) after controlling for HPV vaccination uptake and the sample. In addition, social-psychological determinants largely contributed to the explained variance of HPV vaccination intention of mothers (ΔR2 = .35; p < .001) and daughters (ΔR2 = .34; p < .001). Attitudes, beliefs, subjective norms and habit strength were significantly associated with participants’ HPV vaccination intentions. Conclusions Because of the large contribution of social-psychological variables to the explained variance of HPV vaccination intentions among the mothers and daughters, future communication strategies targeting HPV vaccination uptake should address attitudes, beliefs, subjective norms and habit strength. There is a need for longitudinal research to confirm the causality of the association between these determinants and HPV vaccination behavior indicated by this study. PMID:23388344

Novel Platforms for the Development of a Universal Influenza Vaccine

PubMed Central

Kumar, Arun; Meldgaard, Trine Sundebo; Bertholet, Sylvie

2018-01-01

Despite advancements in immunotherapeutic approaches, influenza continues to cause severe illness, particularly among immunocompromised individuals, young children, and elderly adults. Vaccination is the most effective way to reduce rates of morbidity and mortality caused by influenza viruses. Frequent genetic shift and drift among influenza-virus strains with the resultant disparity between circulating and vaccine virus strains limits the effectiveness of the available conventional influenza vaccines. One approach to overcome this limitation is to develop a universal influenza vaccine that could provide protection against all subtypes of influenza viruses. Moreover, the development of a novel or improved universal influenza vaccines may be greatly facilitated by new technologies including virus-like particles, T-cell-inducing peptides and recombinant proteins, synthetic viruses, broadly neutralizing antibodies, and nucleic acid-based vaccines. This review discusses recent scientific advances in the development of next-generation universal influenza vaccines. PMID:29628926

[Immunisation schedule of the Spanish Association of Paediatrics: 2014 recommendations].

PubMed

Moreno-Pérez, D; Alvarez García, F J; Arístegui Fernández, J; Cilleruelo Ortega, M J; Corretger Rauet, J M; García Sánchez, N; Hernández Merino, A; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

2014-01-01

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded, as routine vaccinations, those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in special situations. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Based on the latest epidemiological trends, CAV-AEP recommends the administration of the first dose of MMR and varicella vaccines at age 12 months, with the second dose at age 2-3 years; the administration of DTaP or Tdap vaccine at age 4-6 years, always followed by another Tdap dose at 11-12 years; and the three meningococcal C scheme at 2 months, 12 months and 12 years of age. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-12 years must be increased. Universal vaccination against varicella in the second year of life is an effective strategy, and the immediate public availability of the vaccine is requested in order to guarantee the right of healthy children to be vaccinated. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. The recently authorised meningococcal B vaccine has opened a chapter of hope in the prevention of this disease. In anticipation of upcoming national and international studies, the Committee recommends the vaccine for the control of disease outbreaks, and insists on the need to be available in pharmacies. Finally, it emphasises the need to bring incomplete vaccinations up to date following the catch-up immunisation schedule. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Direct-acting Antivirals and Host-targeting Agents against the Hepatitis A Virus

PubMed Central

Kanda, Tatsuo; Nakamoto, Shingo; Wu, Shuang; Nakamura, Masato; Jiang, Xia; Haga, Yuki; Sasaki, Reina; Yokosuka, Osamu

2015-01-01

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries. Although effective vaccines for HAV are available, the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists, such as Japan. There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs). Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and infection. Among the HTAs, amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication. Janus kinase (JAK) inhibitors inhibit La protein expression, HAV IRES activity, and HAV replication. Based on this review, both DAAs and HTAs may be needed to control effectively HAV infection, and their use should continue to be explored. PMID:26623267

[Immunisation schedule of the Spanish Association of Paediatrics: 2013 recommendations].

PubMed

Moreno-Pérez, D; Álvarez García, F J; Arístegui Fernández, J; Barrio Corrales, F; Cilleruelo Ortega, M J; Corretger Rauet, J M; González-Hachero, J; Hernández-Sampelayo Matos, T; Merino Moína, M; Ortigosa Del Castillo, L; Ruiz-Contreras, J

2013-01-01

The Advisory Committee on Vaccines of the Spanish Association of Paediatrics (CAV-AEP) updates the immunisation schedule every year, taking into account epidemiological data as well as evidence on the safety, effectiveness and efficiency of vaccines. The present schedule includes levels of recommendation. We have graded as routine vaccinations those that the CAV-AEP consider all children should receive; as recommended those that fit the profile for universal childhood immunisation and would ideally be given to all children, but that can be prioritised according to the resources available for their public funding; and as risk group vaccinations those that specifically target individuals in situations of risk. Immunisation schedules tend to be dynamic and adaptable to ongoing epidemiological changes. Nevertheless, the achievement of a unified immunisation schedule in all regions of Spain is a top priority for the CAV-AEP. Based on the latest epidemiological trends, CAV-AEP follows the innovations proposed in the last year's schedule, such as the administration of the first dose of the MMR and the varicella vaccines at age 12 months and the second dose at age 2-3 years, as well as the administration of the Tdap vaccine at age 4-6 years, always followed by another dose at 11-14 years of age, preferably at 11-12 years. The CAV-AEP believes that the coverage of vaccination against human papillomavirus in girls aged 11-14 years, preferably at 11-12 years, must increase. It reasserts its recommendation to include vaccination against pneumococcal disease in the routine immunisation schedule. Universal vaccination against varicella in the second year of life is an effective strategy and therefore a desirable objective. Vaccination against rotavirus is recommended in all infants due to the morbidity and elevated healthcare burden of the virus. The Committee stresses the need to vaccinate population groups considered at risk against influenza and hepatitis A. Finally, it emphasizes the need to bring incomplete vaccinations up to date following the catch-up immunisation schedule. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier España, S.L. All rights reserved.

The fully synthetic MAG-Tn3 therapeutic vaccine containing the tetanus toxoid-derived TT830-844 universal epitope provides anti-tumor immunity.

PubMed

Laubreton, Daphné; Bay, Sylvie; Sedlik, Christine; Artaud, Cécile; Ganneau, Christelle; Dériaud, Edith; Viel, Sophie; Puaux, Anne-Laure; Amigorena, Sebastian; Gérard, Catherine; Lo-Man, Richard; Leclerc, Claude

2016-03-01

Malignant transformations are often associated with aberrant glycosylation processes that lead to the expression of new carbohydrate antigens at the surface of tumor cells. Of these carbohydrate antigens, the Tn antigen is particularly highly expressed in many carcinomas, especially in breast carcinoma. We designed MAG-Tn3, a fully synthetic vaccine based on three consecutive Tn moieties that are O-linked to a CD4+ T cell epitope, to induce anti-Tn antibody responses that could be helpful for therapeutic vaccination against cancer. To ensure broad coverage within the human population, the tetanus toxoid-derived peptide TT830-844 was selected as a T-helper epitope because it can bind to various HLA-DRB molecules. We showed that the MAG-Tn3 vaccine, which was formulated with the GSK proprietary immunostimulant AS15 and designed for human cancer therapy, is able to induce an anti-Tn antibody response in mice of various H-2 haplotypes, and this response correlates with the ability to induce a specific T cell response against the TT830-844 peptide. The universality of the TT830-844 peptide was extended to new H-2 and HLA-DRB molecules that were capable of binding this T cell epitope. Finally, the MAG-Tn3 vaccine was able to induce anti-Tn antibody responses in cynomolgus monkeys, which targeted Tn-expressing tumor cells and mediated tumor cell death both in vitro and in vivo. Thus, MAG-Tn3 is a highly promising anticancer vaccine that is currently under evaluation in a phase I clinical trial.

Cost-Effectiveness Analysis of Hepatitis B Vaccination Strategies to Prevent Perinatal Transmission in North Korea: Selective Vaccination vs. Universal Vaccination.

PubMed

Lee, Donghoon; Park, Sang Min

2016-01-01

To tackle the high prevalence of Hepatitis B virus (HBV) infection in North Korea, it is essential that birth doses of HBV vaccines should be administered within 24 hours of birth. As the country fails to provide a Timely Birth Dose (TBD) of HBV vaccine, the efforts of reducing the high prevalence of HBV have been significantly hampered. To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective, universal, and the country's current vaccination program against HBV. The cost-effectiveness analysis was performed from societal and payer's perspectives and evaluated by Disability Adjusted Life Year (DALY). The results suggest that introducing the universal vaccination would prevent 1,866 cases of perinatal infections per 100,000 of the birth cohort of 2013. Furthermore, 900 cases of perinatal infections per 100,000 could be additionally averted if switching to the selective vaccination. The current vaccination is a dominated strategy both from the societal and payer's perspective. The Incremental Cost-Effectiveness Ratio (ICER) between universal and selective vaccination is $267 from the societal perspective and is reported as $273 from the payer's perspective. Based on the assumption that the 2012 Gross Domestic Product (GDP) per capita in North Korea, $582.6 was set for cost-effectiveness criteria, the result of this study indicates that selective vaccination may be a highly cost-effective strategy compared to universal vaccination.

Pathotypic characterization of Newcastle disease virus isolated from vaccinated chicken in West Java, Indonesia.

PubMed

Putri, Dwi Desmiyeni; Handharyani, Ekowati; Soejoedono, Retno Damajanti; Setiyono, Agus; Mayasari, Ni Luh Putu Ika; Poetri, Okti Nadia

2017-04-01

This research was conducted to differentiate and characterize eight Newcastle disease virus (NDV) isolates collected from vaccinated chicken at commercial flocks in West Java, Indonesia, in 2011, 2014 and 2015 by pathotype specific primers. A total of eight NDV isolates collected from clinical outbreaks among commercial vaccinated flocks in West Java, Indonesia, in 2011, 2014, and 2015 were used in this study. Reverse transcription-polymerase chain reaction was used to detect and differentiate virulence of NDV strains, using three sets of primers targeting their M and F gene. First primers were universal primers to detect NDV targeting matrix (M) gene. Other two sets of primers were specific for the fusion (F) gene cleavage site sequence of virulent and avirulent NDV strains. Our results showed that three isolates belong to NDV virulent strains, and other five isolates belong to NDV avirulent strains. The nucleotide sequence of the F protein cleavage site showed 112 K/R-R-Q/R-K-R/G-F 117 on NDV virulent strains and 112 G-K/R-Q-G-R-L 117 on NDV avirulent strain. Result from the current study suggested that NDV virulent strain were circulating among vaccinated chickens in West Java, Indonesia; this might possess a risk of causing ND outbreaks and causing economic losses within the poultry industry.

Mind the gaps: what's missing from current economic evaluations of universal HPV vaccination?

PubMed

Marsh, Kevin; Chapman, Ruth; Baggaley, Rebecca F; Largeron, Nathalie; Bresse, Xavier

2014-06-24

Since the original licensing of human papilloma virus (HPV) vaccination for women, evidence is accumulating of its effectiveness in preventing HPV-related conditions in men, and universal vaccination (vaccinating men and women) is now recommended in some countries. Several models of the cost-effectiveness of universal HPV vaccination have been published, but results have been mixed. This article assesses the extent to which economic studies have captured the range of values associated with universal HPV vaccination, and how this influences estimates of its cost-effectiveness. Eight published economic evaluations of universal HPV vaccination were reviewed to identify which of the values associated with universal HPV vaccination were included in each analysis. Studies of the cost-effectiveness of universal HPV vaccination capture only a fraction of the values generated. Most studies focused on impacts on health and health system cost, and only captured these partially. A range of values is excluded from most studies, including impacts on productivity, patient time and costs, carers and family costs, and broader social values such as the right to access treatment. Further, those studies that attempted to capture these values only did so partially. Decisions to invest in universal HPV vaccination need to be based on a complete assessment of the value that it generates. This is not provided by existing economic evaluations. Further work is required to understand this value. First, research is required to understand how HPV-related health outcomes impact on society including, for instance, their impact on productivity. Second, consideration should be given to alternative approaches to capture this broader set of values in a manner useful to decisions-makers, such as multi-criteria decision analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Protection by universal influenza vaccine is mediated by memory CD4 T cells.

PubMed

Valkenburg, Sophie A; Li, Olive T W; Li, Athena; Bull, Maireid; Waldmann, Thomas A; Perera, Liyanage P; Peiris, Malik; Poon, Leo L M

2018-07-05

There is a diverse array of influenza viruses which circulate between different species, reassort and drift over time. Current seasonal influenza vaccines are ineffective in controlling these viruses. We have developed a novel universal vaccine which elicits robust T cell responses and protection against diverse influenza viruses in mouse and human models. Vaccine mediated protection was dependent on influenza-specific CD4 + T cells, whereby depletion of CD4 + T cells at either vaccination or challenge time points significantly reduced survival in mice. Vaccine memory CD4 + T cells were needed for early antibody production and CD8 + T cell recall responses. Furthermore, influenza-specific CD4 + T cells from vaccination manifested primarily Tfh and Th1 profiles with anti-viral cytokine production. The vaccine boosted H5-specific T cells from human PBMCs, specifically CD4 + and CD8 + T effector memory type, ensuring the vaccine was truly universal for its future application. These findings have implications for the development and optimization of T cell activating vaccines for universal immunity against influenza. Copyright © 2018 Elsevier Ltd. All rights reserved.

College and University Compliance With a Required Meningococcal Vaccination Law

PubMed Central

Castel, Amanda D.; Reed, Greg; Davenport, Marsha G.; Harrison, Lee H.; Blythe, David

2015-01-01

Objective Maryland became the first state to pass a vaccination law requiring college and university students living on campus to obtain a meningococcal vaccination or to sign a waiver refusing vaccination because college students are at increased risk for disease. The authors sought to identify how Maryland colleges addressed the law and determine whether schools were in full compliance. Participants The authors surveyed 32 college/university administrators via a self-administered questionnaire. Methods The authors calculated vaccination and waiver rates and assessed compliance with the law overall and with specific law components. Results Among 28 participating schools, annual vaccination rates and waiver rates among students during 2000–2004 ranged from 66%–76% and 12%–17%, respectively. Two (7%) schools were compliant with all components of the law. Conclusions Mandatory vaccination laws do not ensure compliance at the college and university level. Mandatory reporting, increased education, and collaboration between colleges and universities and public health agencies are needed. PMID:17967757

2009–2010 Seasonal Influenza Vaccination Coverage Among College Students From 8 Universities in North Carolina

PubMed Central

Poehling, Katherine A.; Blocker, Jill; Ip, Edward H.; Peters, Timothy R.; Wolfson, Mark

2012-01-01

Objective We sought to describe the 2009–2010 seasonal influenza vaccine coverage of college students. Participants 4090 college students from eight North Carolina universities participated in a confidential, web-based survey in October-November 2009. Methods Associations between self-reported 2009–2010 seasonal influenza vaccination and demographic characteristics, campus activities, parental education, and email usage were assessed by bivariate analyses and by a mixed-effects model adjusting for clustering by university. Results Overall, 20% of students (range 14%–30% by university) reported receiving 2009–2010 seasonal influenza vaccine. Being a freshman, attending a private university, having a college-educated parent, and participating in academic clubs/honor societies predicted receipt of influenza vaccine in the mixed-effects model. Conclusions The self-reported 2009–2010 influenza vaccine coverage was one-quarter of the 2020 Healthy People goal (80%) for healthy persons 18–64 years of age. College campuses have the opportunity to enhance influenza vaccine coverage among its diverse student populations. PMID:23157195

Ethical considerations of universal vaccination against human papilloma virus

PubMed Central

2014-01-01

Background From an epidemiological perspective, the practice of universal vaccination of girls and young women in order to prevent human papilloma virus (HPV) infection and potential development of cervical cancer is widely accepted even though it may lead to the neglect of other preventive strategies against cervical cancer. Discussion It is argued that removing the deterrent effect – the fear of developing cancer – could encourage teenage sex. This paper reflects on the ethical legitimacy of the universal vaccination of girls and young women against HPV infection, especially regarding safety issues, the need to vaccinate people who have opted to abstain from sex, the presumption of early onset of sexual relations, the commercial interests of the companies that manufacture the vaccine, and the recommendation of universal vaccination in males. Summary Based on the aforementioned information, we believe that the universal vaccination against HPV in young women is acceptable from an ethical point of view, given the medical advantages it presents. PMID:24708813

2009-2010 seasonal influenza vaccination coverage among college students from 8 universities in North Carolina.

PubMed

Poehling, Katherine A; Blocker, Jill; Ip, Edward H; Peters, Timothy R; Wolfson, Mark

2012-01-01

The authors sought to describe the 2009-2010 seasonal influenza vaccine coverage of college students. A total of 4,090 college students from 8 North Carolina universities participated in a confidential, Web-based survey in October-November 2009. Associations between self-reported 2009-2010 seasonal influenza vaccination and demographic characteristics, campus activities, parental education, and e-mail usage were assessed by bivariate analyses and by a mixed-effects model adjusting for clustering by university. Overall, 20% of students (range 14%-30% by university) reported receiving 2009-2010 seasonal influenza vaccine. Being a freshman, attending a private university, having a college-educated parent, and participating in academic clubs/honor societies predicted receipt of influenza vaccine in the mixed-effects model. The self-reported 2009-2010 influenza vaccine coverage was one-quarter of the 2020 Healthy People goal (80%) for healthy persons 18 to 64 years of age. College campuses have the opportunity to enhance influenza vaccine coverage among its diverse student populations.

Communication and mass vaccination strategies after pertussis outbreak in rural Amish communities-Illinois, 2009-2010.

PubMed

Medina-Marino, Andrew; Reynolds, Debra; Finley, Carol; Hays, Susan; Jones, Jane; Soyemi, Kenneth

2013-01-01

During January 2010, 2 infants from an Amish community in east-central Illinois were hospitalized with pertussis. The local health department (LDH) intervened to control disease transmission, identify contributing factors, and determine best communications methods to improve vaccination coverage. A retrospective cohort study was conducted using public health surveillance data to determine the extent of the outbreak; the standard Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists case definition for pertussis was used. The standardized Illinois Department of Public Health pertussis patient interview form was used to collect demographic, symptom, vaccination history, and treatment history information. To control disease transmission, LDH staff worked with the Amish community to promote a vaccination campaign during February 6-April 30, 2010. Forty-seven cases were identified, with onsets during December 2009-March 2010. Median age was 7 (interquartile range 1-12) years. Nineteen (40%) patients were male; 39 (83%) were aged <18 years; 37 (79%) had not received any pertussis-containing vaccine. Presenting symptoms did not differ substantially between vaccinated and unvaccinated patients. Duration of cough was longer among unvaccinated than vaccinated patients (32 vs. 15.5 days, P = .002). Compared with vaccinated patients, proportionately more unvaccinated patients reported secondary household transmission (30% vs. 72%; P = .012). Through enhanced vaccination campaigns, 251 (∼10%) Amish community members were administered 254 pertussis-containing vaccines. Targeted health communication and outreach resulted in a successful vaccine campaign and long-running monthly vaccination clinic. Amish do not universally reject vaccines, and their practices regarding vaccination are not static. No claim to original US government works.

The impact of varicella vaccination on varicella-related hospitalization rates: global data review

PubMed Central

Hirose, Maki; Gilio, Alfredo Elias; Ferronato, Angela Esposito; Ragazzi, Selma Lopes Betta

2016-01-01

Abstract Objective: To describe the impact of varicella vaccination on varicella-related hospitalization rates in countries that implemented universal vaccination against the disease. Data source: We identified countries that implemented universal vaccination against varicella at the http://apps.who.int/immunization_monitoring/globalsummary/schedules site of the World Health Organization and selected articles in Pubmed describing the changes (pre/post-vaccination) in the varicella-related hospitalization rates in these countries, using the Keywords "varicella", "vaccination/vaccine" and "children" (or) "hospitalization". Publications in English published between January 1995 and May 2015 were included. Data synthesis: 24 countries with universal vaccination against varicella and 28 articles describing the impact of the vaccine on varicella-associated hospitalizations rates in seven countries were identified. The US had 81.4%–99.2% reduction in hospitalization rates in children younger than four years, 6–14 years after the onset of universal vaccination (1995), with vaccination coverage of 90%; Uruguay: 94% decrease (children aged 1–4 years) in six years, vaccination coverage of 90%; Canada: 93% decrease (age 1–4 years) in 10 years, coverage of 93%; Germany: 62.4% decrease (age 1–4 years) in 8 years, coverage of 78.2%; Australia: 76.8% decrease (age 1–4 years) in 5 years, coverage of 90%; Spain: 83.5% decrease (age <5 years) in four years, coverage of 77.2% and Italy 69.7%–73.8% decrease (general population), coverage of 60%–95%. Conclusions: The publications showed variations in the percentage of decrease in varicella-related hospitalization rates after universal vaccination in the assessed countries; the results probably depend on the time since the implementation of universal vaccination, differences in the studied age group, hospital admission criteria, vaccination coverage and strategy, which does not allow direct comparison between data. PMID:26965075

The impact of varicella vaccination on varicella-related hospitalization rates: global data review.

PubMed

Hirose, Maki; Gilio, Alfredo Elias; Ferronato, Angela Esposito; Ragazzi, Selma Lopes Betta

2016-09-01

to describe the impact of varicella vaccination on varicella-related hospitalization rates in countries that implemented universal vaccination against the disease. we identified countries that implemented universal vaccination against varicella at the http://apps.who.int/immunization_monitoring/globalsummary/schedules site of the World Health Organization and selected articles in Pubmed describing the changes (pre/post-vaccination) in the varicella-related hospitalization rates in these countries, using the Keywords "varicella", "vaccination/vaccine" and "children" (or) "hospitalization". Publications in English published between January 1995 and May 2015 were included. 24 countries with universal vaccination against varicella and 28 articles describing the impact of the vaccine on varicella-associated hospitalizations rates in seven countries were identified. The US had 81.4% -99.2% reduction in hospitalization rates in children younger than four years after 6-14 years after the onset of universal vaccination (1995), with vaccination coverage of 90%; Uruguay: 94% decrease (children aged 1-4 years) in six years, vaccination coverage of 90%; Canada: 93% decrease (age 1-4 years) in 10 years, coverage of 93%; Germany: 62.4% decrease (age 1-4 years) in 8 years, coverage of 78.2%; Australia: 76.8% decrease (age 1-4 years) in 5 years, coverage of 90%; Spain: 83.5% decrease (age <5 years) in four years, coverage of 77.2% and Italy 69.7% -73.8% decrease (general population), coverage of 60%-95%. The publications showed variations in the percentage of decrease in varicella-related hospitalization rates after universal vaccination in the assessed countries; the results probably depend on the time since the implementation of universal vaccination, differences in the studied age group, hospital admission criteria, vaccination coverage and strategy, which does not allow direct comparison between data. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Pros, cons, and ethics of HPV vaccine in teens-Why such controversy?

PubMed

White, Mark Donald

2014-12-01

Human papillomavirus (HPV) infection remains one of the most commonly sexually transmitted infections in both females and males. HPV viruses are associated with several manifestations including genital warts, but more importantly for urology practitioners, cervical and penile carcinomas and recurrent genital condylomata in both sexes. The incidence of HPV-related carcinomas has increased in cervical, oropharyngeal, vulvar, penile, and anal cancers. Effective vaccines have been available for almost a decade, but widespread adoption of vaccine administration has been problematic for multiple reasons. Many countries (over 100) have adopted vaccine programs for females and an increasing number of countries are extending the indications to include males between the ages of 9-26. There still seems to be controversy surrounding these universal vaccination programs as well as some ethical and practical concerns regarding the administration of a vaccine for diseases that are associated with sexual contact in both sexes, especially during the early adolescent years. The objective was to provide a review of the available literature so pediatric and adult urologists may be more aware of the issues related to HPV vaccination in order to more effectively counsel patients and parents regarding the risks, benefits, and public health issues regarding HPV vaccination. This topic is especially relevant to pediatric urologists who see patients in the target age group for the HPV vaccine. There has been an explosion of literature regarding HPV vaccination programs and the relative difficulty in adopting the vaccine series with a completion rate of under 50% of patients in the recommended age ranges for vaccination. Articles were obtained from an extensive Medline literature search (1998-present) to evaluate the current HPV vaccination regimens for teenagers with special emphasis on the urologically focused disease burden. The adoption of universal HPV vaccination has been difficult, but appears to be increasing over time as public education improves and governmentally- mandated vaccine programs increase. Despite the ethical concerns raised, the benefits of vaccination with regard to cancer prevention outweigh the risks and potential side effects related to the quadrivalent vaccine administration. Clearly, more follow-up over time is required to document these improvements in public health. Urologists need to remain aware of the prevention strategies for HPV infection and should help with counseling parents and patients in the appropriate age groups for HPV vaccination. Urology providers need to help engage and educate the parents and teenage patients to help promote broader adoption of the HPV vaccine regimen.

Highly targeted cholera vaccination campaigns in urban setting are feasible: The experience in Kalemie, Democratic Republic of Congo

PubMed Central

Massing, Louis Albert; Aboubakar, Soumah; Page, Anne-Laure; Cohuet, Sandra; Ngandwe, Adalbert; Mukomena Sompwe, Eric; Ramazani, Romain; Allheimen, Marcela; Levaillant, Philippe; Lechevalier, Pauline; Kashimi, Marie; de la Motte, Axelle; Calmejane, Arielle; Bouhenia, Malika; Dabire, Ernest; Bompangue, Didier; Kebela, Benoit; Porten, Klaudia

2018-01-01

Introduction Oral cholera vaccines are primarily recommended by the World Health Organization for cholera control in endemic countries. However, the number of cholera vaccines currently produced is very limited and examples of OCV use in endemic countries, and especially in urban settings, are scarce. A vaccination campaign was organized by Médecins Sans Frontières and the Ministry of Health in a highly endemic area in the Democratic Republic of Congo. This study aims to describe the vaccine coverage achieved with this highly targeted vaccination campaign and the acceptability among the vaccinated communities. Methods and findings We performed a cross-sectional survey using random spatial sampling. The study population included individuals one year old and above, eligible for vaccination, and residing in the areas targeted for vaccination in the city of Kalemie. Data sources were household interviews with verification by vaccination card. In total 2,488 people were included in the survey. Overall, 81.9% (95%CI: 77.9–85.3) of the target population received at least one dose of vaccine. The vaccine coverage with two doses was 67.2% (95%CI: 61.9–72.0) among the target population. The vaccine coverage was higher during the first round (74.0, 95%CI: 69.3–78.3) than during the second round of vaccination (69.1%, 95%CI: 63.9–74.0). Vaccination coverage was lower in male adults. The main reason for non-vaccination was to be absent during the campaign. No severe adverse events were notified during the interviews. Conclusions Cholera vaccination campaigns using highly targeted strategies are feasible in urban settings. High vaccination coverage can be obtained using door to door vaccination. However, alternative strategies should be considered to reach non-vaccinated populations like male adults and also in order to improve the efficiency of the interventions. PMID:29734337

Global challenges of implementing human papillomavirus vaccines

PubMed Central

2011-01-01

Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing) of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening. PMID:21718495

Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake.

PubMed

Malhi, Gurtej; Rumman, Amir; Thanabalan, Reka; Croitoru, Kenneth; Silverberg, Mark S; Hillary Steinhart, A; Nguyen, Geoffrey C

2015-06-01

Immunomodulators and biological agents, used to treat inflammatory bowel disease [IBD], are associated with an increased risk of infection, including vaccine-preventable infections. We assessed patient attitudes towards vaccination, knowledge of vaccine recommendations, and uptake of recommended vaccines. Patients attending IBD clinics completed a self-administered, structured, paper-based questionnaire. We collected demographic data, medical and immunisation history, self-reported patient uptake, knowledge, and perceptions of childhood and adult vaccinations. The prevalence of treatment with biologicals, steroids, thiopurines, and methotrexate among the 300 respondents were 37.3%, 16.0%, 16.0%, and 5.7%, respectively. Self-reported vaccine completion was reported by 45.3% of patients. Vaccination uptake rates were 61.3% for influenza, 10.3% for pneumococcus, 61.0% for hepatitis B, 52.0% for hepatitis A, 26.0% for varicella, 20.7% for meningococcus, 5.3% for herpes zoster, and 11.0% for herpes papilloma virus [females only]. Significant predictors of vaccine completion were annual vaccination review by family physician (odds ratio [OR] = 1.82) or gastroenterologist [OR = 1.72], current steroid use [OR = 1.28], and current or prior treatment with biologicals [OR = 1.42]. The majority of patients reported that the primary responsibility to ensure vaccine completion lies with the patient [41.7%] and the family physician [32.3%]. Uncertainty about indications, fears of side effects, and concerns regarding vaccine safety were the most commonly reported reasons for non-uptake [22.0%, 20.7%, and 5.3%, respectively]. Uptake of recommended vaccines among IBD patients is suboptimal. Annual vaccination reviews by both family physician and gastroenterologist may improve vaccine uptake. Interventions targeted at improving vaccination uptake in IBD patients are needed. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Awareness and Knowledge Levels of Turkish College Students about Human Papilloma Virus Infection and Vaccine Acceptance.

PubMed

Oz, Murat; Cetinkaya, Nilufer; Apaydin, Aysen; Korkmaz, Elmas; Bas, Sevda; Ozgu, Emre; Gungor, Tayfun

2018-04-01

Awareness of HPV by the target population is an important determinant of vaccine acceptance. The aim of this study is to evaluate the awareness of HPV infection and acceptability of the HPV vaccines among Turkish college students. College students aged 18-30 who were attending a large public university in Ankara participated in this study. The participants were asked to complete a questionnaire to elicit demographic characteristics, awareness level of HPV and HPV vaccine, and willingness to be vaccinated. One thousand one hundred sixty students responded to the invitation email and completed the questionnaire. The mean scores of female students about HPV and HPV vaccine were 7.1/15 and 3.6/9, respectively, while these scores were 7.9/15 and 3.4/9 among male students, respectively. While 51 % percent of female and 33.5 % of male students had heard of HPV and 32.8 % and 18 % of them had heard of HPV vaccine, respectively, only 1.5 % of female and 0.4 % of male students had been vaccinated against HPV. A total of 507 students (43.7 %) had previously heard of HPV. Only 309 (26.6 %) of the participants had previously heard of the HPV vaccine, and 45.1 % of the students were willing to receive HPV vaccination. The main predictors for willingness to be vaccinated were the following: sexual experience, sexual behavior, past history of sexually transmitted infection (STI), and knowledge about HPV and HPV vaccine. Higher awareness levels of HPV and HPV vaccine are significantly related to greater willingness to be vaccinated, and the main reasons for rejecting the vaccine were insufficient information about the vaccine and possible unknown side effects.

Cost-Effectiveness Analysis of Hepatitis B Vaccination Strategies to Prevent Perinatal Transmission in North Korea: Selective Vaccination vs. Universal Vaccination

PubMed Central

Lee, Donghoon; Park, Sang Min

2016-01-01

Background To tackle the high prevalence of Hepatitis B virus (HBV) infection in North Korea, it is essential that birth doses of HBV vaccines should be administered within 24 hours of birth. As the country fails to provide a Timely Birth Dose (TBD) of HBV vaccine, the efforts of reducing the high prevalence of HBV have been significantly hampered. Methods To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective, universal, and the country’s current vaccination program against HBV. The cost-effectiveness analysis was performed from societal and payer’s perspectives and evaluated by Disability Adjusted Life Year (DALY). Results The results suggest that introducing the universal vaccination would prevent 1,866 cases of perinatal infections per 100,000 of the birth cohort of 2013. Furthermore, 900 cases of perinatal infections per 100,000 could be additionally averted if switching to the selective vaccination. The current vaccination is a dominated strategy both from the societal and payer’s perspective. The Incremental Cost-Effectiveness Ratio (ICER) between universal and selective vaccination is $267 from the societal perspective and is reported as $273 from the payer’s perspective. Conclusion Based on the assumption that the 2012 Gross Domestic Product (GDP) per capita in North Korea, $582.6 was set for cost-effectiveness criteria, the result of this study indicates that selective vaccination may be a highly cost-effective strategy compared to universal vaccination. PMID:27802340

[HPV prophylactic vaccine coverage in France: Results of a survey among high school and university students in Marseilles' area].

PubMed

Sabiani, L; Bremond, A; Mortier, I; Lecuyer, M; Boubli, L; Carcopino, X

2012-04-01

To assess HPV prophylactic vaccine coverage among French high school and university students as well as their level of education about this vaccine. An anonymous survey was conducted among 2500 high school and university students from the area of Marseilles, France, from December 2009 to April 2010. A total of 2018 questionnaires were collected (80.7% participation rate). Mean age of participants was 20 years (range, 15-45 years). Only 671 (35.4%) participants reported having been vaccinated against HPV, of whom 510 (73.4%) had completed the three injections scheme. Practice of cytological cervical cancer screening was not significantly influenced by vaccination status. Thus, 578 (45.2%) participants who had not been vaccinated already had had a cervical cytology performed, versus 295 (43.3%) vaccinated ones (P=0.445). Among those not being vaccinated, 671 (49.8%) fulfilled criteria for a catch-up vaccination, of whom only 325 (48.4%) agreed for such a catch-up. Main reasons given for refusal for a catch-up vaccination were the lack of information about HPV vaccine and fear of side effects. In total, 1722 (90%) considered themselves as educated about the HPV vaccine. Source of education was attributed to doctors and media by 54.4% and 53.7% of participants, respectively. Educational role attributed to school and university was poor (3.4%). Despite apparent satisfactory level of education, HPV prophylactic vaccine coverage among high school and university students appears to be insufficient. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Adjuvants and alternative routes of administration towards the development of the ideal influenza vaccine.

PubMed

Durando, Paolo; Iudici, Rocco; Alicino, Cristiano; Alberti, Marisa; de Florentis, Daniela; Ansaldi, Filippo; Icardi, Giancarlo

2011-01-01

Vaccination is universally considered as the principal measure for the control of influenza, which represents a significant burden worldwide, both from a health-care and a socio-economic viewpoint. Conventional non-adjuvanted trivalent influenza vaccines (TIVs) have been recognized as having some deficiencies, such as suboptimal immunogenicity particularly in the elderly, in patients with severe chronic diseases and immunocompromized, indeed, those groups of the population at higher risk of developing severe complications following influenza infection, when compared to healthy adults. Moreover, the protection offered by conventional vaccines may be reduced by periodic antigenic drifts, resulting in a mismatch between the circulating and vaccinal viral strains. Another gap regarding currently available vaccines is related to the egg-based manufacturing system for their production: not only the length of time involved with the latter but also the limited capacity of this platform technology represent a major limitation for the active prevention of influenza, which is particularly important in the case of a new pandemic strain. New technologies used in vaccine composition, administration and manufacture have led to major advances during the last few years, and clinical researchers have continued to work hard, investigating several different strategies to improve the performance of influenza vaccines: namely, the addition of different adjuvants (i.e., MF59- and AS03-vaccines, virosomal formulations), the use of alternative routes of administration or manufacture (i.e., intradermal, nasal and oral vaccines and cell culture- and reverse genetic-based vaccines) or of high doses of antigen, and the development of DNA-vaccines, or the use of conserved viral epitopes (i.e., the extracellular portion of the M2 protein, the nucleoprotein and some domains of the hemagglutinin), in the attempt to produce a "universal target" antigen vaccine. The knowledge acquired represents a fundamental challenge for the control of influenza. An overview of the most recent and interesting results, some of which gained from our own research experience, particularly concerning two successful approaches, of those outlined above, namely the use of: (i) the oil-in-water MF59-adjuvant, and (ii) the intradermal (ID) route for vaccine administration, through a novel microinjection system, will be reported and discussed, together with the possible implications and perspectives to optimize immunization policies against influenza in the near future.

Ambiguous Capture: Collaborative Capitalism and the Meningitis Vaccine Project

PubMed Central

Graham, Janice

2016-01-01

ABSTRACT The primary health care approach advanced at Alma Ata to address social determinants of health was replaced by selective health care a year later at Bellagio. Subsequently, immunization was endorsed as a cost-effective technical intervention to combat targeted infectious diseases. Multilateral efforts to collaborate on immunization as a universal public health good ambiguously capture the interests of the world’s governments as well as private, public, and not-for-profit institutions. Global assemblages of scientists, governments, industry and nongovernmental organizations now work in public-private partnerships to develop and make essential vaccines accessible, with vaccines marketed as single fix solutions for global health. Drawing from ethnographic fieldwork in France and Burkina Faso that followed the development, regulation, and implementation of the group A meningococcal conjugate vaccine for sub-Saharan Africa, in this article I describe events during and after the development of MenAfriVac. A technological success narrative steeped in collaborative capitalist rhetoric disguises neglected health care systems. PMID:27027575

Ambiguous Capture: Collaborative Capitalism and the Meningitis Vaccine Project.

PubMed

Graham, Janice

2016-01-01

The primary health care approach advanced at Alma Ata to address social determinants of health was replaced by selective health care a year later at Bellagio. Subsequently, immunization was endorsed as a cost-effective technical intervention to combat targeted infectious diseases. Multilateral efforts to collaborate on immunization as a universal public health good ambiguously capture the interests of the world's governments as well as private, public, and not-for-profit institutions. Global assemblages of scientists, governments, industry and nongovernmental organizations now work in public-private partnerships to develop and make essential vaccines accessible, with vaccines marketed as single fix solutions for global health. Drawing from ethnographic fieldwork in France and Burkina Faso that followed the development, regulation, and implementation of the group A meningococcal conjugate vaccine for sub-Saharan Africa, in this article I describe events during and after the development of MenAfriVac. A technological success narrative steeped in collaborative capitalist rhetoric disguises neglected health care systems.

Impact of Sylvatic Plague Vaccine on Non-target Small Rodents in Grassland Ecosystems.

PubMed

Bron, Gebbiena M; Richgels, Katherine L D; Samuel, Michael D; Poje, Julia E; Lorenzsonn, Faye; Matteson, Jonathan P; Boulerice, Jesse T; Osorio, Jorge E; Rocke, Tonie E

2018-05-09

Oral vaccination is an emerging management strategy to reduce the prevalence of high impact infectious diseases within wild animal populations. Plague is a flea-borne zoonosis of rodents that often decimates prairie dog (Cynomys spp.) colonies in the western USA. Recently, an oral sylvatic plague vaccine (SPV) was developed to protect prairie dogs from plague and aid recovery of the endangered black-footed ferret (Mustela nigripes). Although oral vaccination programs are targeted toward specific species, field distribution of vaccine-laden baits can result in vaccine uptake by non-target animals and unintended indirect effects. We assessed the impact of SPV on non-target rodents at paired vaccine and placebo-treated prairie dog colonies in four US states from 2013 to 2015. Bait consumption by non-target rodents was high (70.8%, n = 3113), but anti-plague antibody development on vaccine plots was low (23.7%, n = 266). In addition, no significant differences were noted in combined deer mice (Peromyscus maniculatus) and western harvest mouse (Reithrodontomys megalotis) abundance or community evenness and richness of non-target rodents between vaccine-treated and placebo plots. In our 3-year field study, we could not detect a significant positive or negative effect of SPV application on non-target rodents.

Meningococcal vaccination in primary care amongst adolescents in North West England: an ecological study investigating associations with general practice characteristics.

PubMed

Blagden, Sarah; Hungerford, Daniel; Limmer, Mark

2018-01-27

In 2015 the meningococcal ACWY (MenACWY) vaccination was introduced amongst adolescents in England following increased incidence and mortality associated with meningococcal group W. MenACWY vaccination uptake data for 17-18 years old and students delivered in primary care were obtained for 20 National Health Service clinical commissioning groups (CCGs) via the ImmForm vaccination system. Data on general practice characteristics, encompassing demographics and patient satisfaction variables, were extracted from the National General Practice Profiles resource. Univariable analysis of the associations between practice characteristics and vaccination was performed, followed by multivariable negative binomial regression. Data were utilized from 587 general practices, accounting for ~8% of all general practices in England. MenACWY vaccination uptake varied from 20.8% to 46.8% across the CCGs evaluated. Upon multivariable regression, vaccination uptake increased with increasing percentage of patients from ethnic minorities, increasing percentage of patients aged 15-24 years, increasing percentage of patients that would recommend their practice and total Quality and Outcomes Framework achievement for the practice. Conversely, vaccination uptake decreased with increasing deprivation. This study has identified several factors independently associated with MenACWY vaccination in primary care. These findings will enable a targeted approach to improve general practice-level vaccination uptake. © The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Hospitalizations for pneumonia, invasive diseases and otitis in Tuscany (Italy), 2002-2014: Which was the impact of universal pneumococcal pediatric vaccination?

PubMed

Boccalini, Sara; Varone, Ornella; Chellini, Martina; Pieri, Luca; Sala, Antonino; Berardi, Cesare; Bonanni, Paolo; Bechini, Angela

2017-02-01

Streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. Since 2008 in Tuscany, central Italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched to 13-valent vaccine in 2010) was actively offered free of charge to all newborns. Aim of the study is to evaluate the impact of pneumococcal pediatric vaccination in the Tuscan population on hospitalizations potentially caused by S. pneumoniae, during pre-vaccination (PVP, 2002-2007) and vaccination period (VP, 2009-2014). We analyzed hospital discharge records (HDRs) of all hospitals in Tuscany from 2002 to 2014. Hospitalizations potentially due to pneumococcal diseases were 347, 221. The general hospitalization rate was 716/100,000 inhabitants during PVP and 753/100,000 in VP, with a decrease of 29.1% in the age-group 0-9 y ("target" of the vaccination program) and an increase of 75.7% in subjects >64 y of age. During VP, admission days and hospitalization costs increased (6.2% and 24.2%, respectively), especially in patients >64 y (12.9% and 33.8%, respectively); in children <10 y decreased by 21.2% and 12.8%, respectively. The pneumococcal pediatric vaccination resulted in the decrease of hospitalizations in younger but the expected indirect effect in the elderly was not reported, justifying the Tuscan recommendation to extend the vaccination to subjects > 64 y.

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

PubMed

Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

PubMed

Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

2017-11-02

Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil.

PubMed

de Soárez, Patrícia Coelho; Sartori, Ana Marli Christovam; Freitas, Angela Carvalho; Nishikawa, Álvaro Mitsunori; Novaes, Hillegonda Maria Dutilh

2015-01-01

To evaluate the cost-effectiveness of introducing universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) into the National Immunization Program (NIP) in Brazil. Economic evaluation using a Markov model to compare two strategies: (1) universal vaccination of adults aged 60 years with one dose of PPV23 and 2) current practice (vaccination of institutionalized elderly and elderly with underlying diseases). The perspective was from the health system and society. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Clinical syndromes of interest were invasive pneumococcal disease (IPD) including meningitis, sepsis and others and pneumonia. Vaccine efficacy against IPD was obtained from a meta-analysis of randomized control trials and randomized studies, whereas vaccine effectiveness against pneumonia was obtained from cohort studies. Resource utilization and costs were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS). Univariate and multivariate sensitivity analysis were performed. The universal vaccination strategy avoided 7,810 hospitalizations and 514 deaths, saving 3,787 years of life and costing a total of USD$31,507,012 and USD$44,548,180, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$1,297 per LYS, from the perspective of the health system, and USD$904 per LYS, from the societal perspective. The results suggest that universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is a very cost-effective intervention for preventing hospitalization and deaths for IPD and pneumonia is this age group in Brazil.

Influences on university students’ intention to receive recommended vaccines: a cross-sectional survey

PubMed Central

Landowska, Kate; Waller, Jo; Bedford, Helen; Rockliffe, Lauren; Forster, Alice S

2017-01-01

Objectives To explore predictors of university students’ intention to receive a recommended vaccine and the main sources of vaccine-related information accessed by university students. Setting Participants were recruited from University College London (UK) in summer 2015. Participants 177 university students participated. The majority of participants were female (58%), White (68%) and had no religion (58%). Participants were aged 18 to 42 (mean age=23.6). Primary and secondary outcome measures Primary outcome measures included vaccine attitude, perceived subjective norm, perceived behavioural control, perceived self-efficacy, past receipt of recommended childhood vaccines, perceived adverse reaction to past vaccination and needle fear. As a secondary outcome sources of vaccine-related information were assessed. Results Students classified as high intenders were more likely to have received all recommended childhood vaccines (OR 3.57; 95% CI 1.21 to 10.59; p=0.022), be less afraid of needles (OR 2.44; 95% CI 1.12 to 5.36; p=0.026) and to have lived in the UK until at least the age of 4 compared with those not living in the UK until at least the age of 4 (OR 0.39; 95% CI 0.18 to 0.83; p=0.015) and those who lived both in the UK and elsewhere (OR 0.42; 95% CI 0.04 to 4.06; p=0.424). The multivariable model explained 25.5% of variance in intention to receive a recommended vaccine. The internet was the most commonly reported source of vaccination information. Conclusions Findings provide an indication of the factors that may need to be addressed by interventions aiming to increase uptake of recommended vaccines in a university population. Future research is recommended using a prospective cohort design. PMID:28733302

Effectiveness of Early Measles, Mumps, and Rubella Vaccination Among 6-14-Month-Old Infants During an Epidemic in the Netherlands: An Observational Cohort Study.

PubMed

Woudenberg, Tom; van der Maas, Nicoline A T; Knol, Mirjam J; de Melker, Hester; van Binnendijk, Rob S; Hahné, Susan J M

2017-04-15

Routinely, the first measles, mumps, and rubella (MMR) vaccine dose is given at 14 months of age in the Netherlands. However, during a measles epidemic in 2013-2014, MMR vaccination was also offered to 6-14-month-olds in municipalities with <90% MMR vaccination coverage. We studied the effectiveness of the early MMR vaccination schedule. Parents of all infants targeted for early MMR vaccination were asked to participate. When parent(s) suspected measles, their infant's saliva was tested for measles-specific antibodies. The vaccine effectiveness (VE) against laboratory-confirmed and self-reported measles was estimated using Cox regression, with VE calculated as 1 minus the hazard ratio. Three vaccinated and 10 unvaccinated laboratory-confirmed cases occurred over observation times of 106631 and 23769 days, respectively. The unadjusted VE against laboratory-confirmed measles was 94% (95% confidence interval [CI], 79%-98%). After adjustment for religion and sibling's vaccination status, the VE decreased to 71% (-72%-95%). For self-reported measles, the unadjusted and adjusted VE was 67% (40%-82%) and 43% (-12%-71%), respectively. Infants vaccinated between 6 and 14 months of age had a lower risk of measles than unvaccinated infants. However, part of the effect was caused by herd immunity, since vaccinated infants were more likely to be surrounded by other vaccinated individuals. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Revisiting knowledge, attitudes and practice (KAP) on human papillomavirus (HPV) vaccination among female university students in Hong Kong.

PubMed

Leung, Jonathan Tin Chi; Law, Chi-Kin

2018-04-03

Despite cervical cancer can be preventable by HPV vaccination, little is known on its associated factors among young females in Hong Kong. This study aimed to investigate the present situation regarding the self-reported knowledge, attitudes and practice (KAP) of Human Papillomavirus (HPV) vaccination and to examine their associated factors among female university students in Hong Kong. 195 respondents were recruited to complete a self-administered questionnaire from two local universities through convenience sampling. 8.2% respondents indicated that family doctors as sources of knowledge of HPV and HPV vaccination. 59.0% of the sample identified more than four knowledge items, 82.6% thought that HPV vaccines can effectively prevent cervical cancer and 47.2% received HPV vaccination. Regression analyses found those at older age, thought that they might be infected by HPV and received HPV would have a higher level of knowledge. Those who knew HPV is sexually transmitted, thought may be infected by HPV and received HPV vaccination would have positive attitude on HPV vaccination. Those at older ages, knew their university provided discounted vaccination for female students, and were not afraid of the side effects were associated with HPV vaccination. Family doctors should take a more prominent role in disseminating accurate and precise information. Advocacies should be emphasised on the risk of HPV as a sexually transmitted disease and the availability of discounted and safe HPV vaccines in tertiary educational institutions to increase the uptake rate of HPV vaccines for first-year and non-health major university students.

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.

[Seroprevalence of varicella-zoster virus antibodies after the recent introduction of the universal childhood immunisation schedule in the Community of Madrid].

PubMed

García-Comas, Luis; Ordobás Gavín, María; Sanz Moreno, Juan Carlos; Ramos Blázquez, Belén; Gutiérrez Rodríguez, M Angeles; Barranco Ordóñez, Dolores

2016-12-01

In November 2006, the Community of Madrid included the chickenpox vaccine into the immunisation schedule for children from 15 months of age. This was withdrawn in January 2014. Seroprevalence of antibodies to the virus is estimated after the first 2-3 years from the inclusion of the vaccine, and as well as its evolution since 1999. A cross-sectional study was conducted on the target population consisting of residents in the Community of Madrid between 2 and 60 years of age. Measurement of IgG antibodies was performed using an ELISA technique. Seroprevalence was estimated according to sociodemographic characteristics using multiple logistic regressions. The results are compared with previous surveys. Also, the seroprevalence and geometric mean of the antibody according immunisation status and history of the disease are presented. The confidence level used is 95%. A total of 4,378 subjects were included, with a response rate of 69%. The estimated seroprevalence was 95.3% (95% CI: 94.6% - 95.9%). Over 90% of children from the age of 10 have antibodies. The seroprevalence was higher in people with less education. The seroprevalence of immunity vaccine exceeds 90% in the first year after vaccination, but in the second year decreased to 82.6% (95% CI 56.0 - 94.7). Significant differences, attributable to universal vaccination, were found compared to previous surveys. Continued surveillance is needed in order to assess the impact of the withdrawal of the recommendation to vaccinate at 15 months. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Vaccine chronicle in Japan.

PubMed

Nakayama, Tetsuo

2013-10-01

The concept of immunization was started in Japan in 1849 when Jenner's cowpox vaccine seed was introduced, and the current immunization law was stipulated in 1948. There have been two turning points for amendments to the immunization law: the compensation remedy for vaccine-associated adverse events in 1976, and the concept of private vaccination in 1994. In 1992, the regional Court of Tokyo, not the Supreme Court, decided the governmental responsibility on vaccine-associated adverse events, which caused the stagnation of vaccine development. In 2010, many universal vaccines became available as the recommended vaccines, but several vaccines, including mumps, zoster, hepatitis B, and rota vaccines, are still voluntary vaccines, not universal routine applications. In this report, immunization strategies and vaccine development are reviewed for each vaccine item and future vaccine concerns are discussed.

Strategies and actions of multi-purpose health communication on vaccine preventable infectious diseases in order to increase vaccination coverage in the population: The ESCULAPIO project

PubMed Central

Bonanni, Paolo; Lauri, Sara; Tiscione, Emilia; Levi, Miriam; Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico; Gasparini, Roberto; Panatto, Donatella; Amicizia, Daniela; Coppola, Rosa Cristina; Vitale, Francesco; Iannazzo, Stefania

2017-01-01

ABSTRACT The ESCULAPIO Project aims at increasing awareness on vaccine preventable infectious diseases (VPID) and vaccinations in different target populations and to spread the culture of prevention. Information/training interventions on VPID have been developed and health promotion activities for the general population, students and their parents, teachers and health care workers (HCWs) were set up. In Tuscany, educational courses on VPID in high schools were organized and students were stimulated to prepare informative materials on VPID for lower grade school pupils. In Liguria, an educational card game (named ‘Vaccine at the Fair’) was presented to children of primary schools. Stands in shopping centers were used in Palermo to distribute the regional vaccination schedule and gadgets, also providing indications on reliable websites where to find correct information on vaccinations. A music video played by health care workers (HCWs) was created and used in the University Hospital of Cagliari to promote the anti-flu vaccination campaign in HCWs. In Apulia, meetings with the general population were organized to collect controversial issues about vaccinations and a national call center was launched to create a direct line from the general population to experts in vaccines and vaccination strategies. In Veneto, meetings in the birth centers and home visits for subjects refusing vaccination have been organized. All activities are useful and effective tools to increase knowledge about VPID and confidence in vaccination, which are crucial aspects in order to increase vaccine uptake. The project was funded by the Italian Ministry of Health, Center for Disease Prevention and Control (CCM) in 2013. PMID:28215120

Strategies and actions of multi-purpose health communication on vaccine preventable infectious diseases in order to increase vaccination coverage in the population: The ESCULAPIO project.

PubMed

Bechini, Angela; Bonanni, Paolo; Lauri, Sara; Tiscione, Emilia; Levi, Miriam; Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico; Gasparini, Roberto; Panatto, Donatella; Amicizia, Daniela; Coppola, Rosa Cristina; Pellizzari, Barbara; Tabacchi, Garden; Costantino, Claudio; Vitale, Francesco; Iannazzo, Stefania; Boccalini, Sara

2017-02-01

The ESCULAPIO Project aims at increasing awareness on vaccine preventable infectious diseases (VPID) and vaccinations in different target populations and to spread the culture of prevention. Information/training interventions on VPID have been developed and health promotion activities for the general population, students and their parents, teachers and health care workers (HCWs) were set up. In Tuscany, educational courses on VPID in high schools were organized and students were stimulated to prepare informative materials on VPID for lower grade school pupils. In Liguria, an educational card game (named 'Vaccine at the Fair') was presented to children of primary schools. Stands in shopping centers were used in Palermo to distribute the regional vaccination schedule and gadgets, also providing indications on reliable websites where to find correct information on vaccinations. A music video played by health care workers (HCWs) was created and used in the University Hospital of Cagliari to promote the anti-flu vaccination campaign in HCWs. In Apulia, meetings with the general population were organized to collect controversial issues about vaccinations and a national call center was launched to create a direct line from the general population to experts in vaccines and vaccination strategies. In Veneto, meetings in the birth centers and home visits for subjects refusing vaccination have been organized. All activities are useful and effective tools to increase knowledge about VPID and confidence in vaccination, which are crucial aspects in order to increase vaccine uptake. The project was funded by the Italian Ministry of Health, Center for Disease Prevention and Control (CCM) in 2013.

Human Immunity and the Design of Multi-Component, Single Target Vaccines

PubMed Central

Saul, Allan; Fay, Michael P.

2007-01-01

Background Inclusion of multiple immunogens to target a single organism is a strategy being pursued for many experimental vaccines, especially where it is difficult to generate a strongly protective response from a single immunogen. Although there are many human vaccines that contain multiple defined immunogens, in almost every case each component targets a different pathogen. As a consequence, there is little practical experience for deciding where the increased complexity of vaccines with multiple defined immunogens vaccines targeting single pathogens will be justifiable. Methodology/Principal Findings A mathematical model, with immunogenicity parameters derived from a database of human responses to established vaccines, was used to predict the increase in the efficacy and the proportion of the population protected resulting from addition of further immunogens. The gains depended on the relative protection and the range of responses in the population to each immunogen and also to the correlation of the responses between immunogens. In most scenarios modeled, the gain in overall efficacy obtained by adding more immunogens was comparable to gains obtained from a single immunogen through the use of better formulations or adjuvants. Multi-component single target vaccines were more effective at decreasing the proportion of poor responders than increasing the overall efficacy of the vaccine in a population. Conclusions/Significance Inclusion of limited number of antigens in a vaccine aimed at targeting a single organism will increase efficacy, but the gains are relatively modest and for a practical vaccine there are constraints that are likely to limit multi-component single target vaccines to a small number of key antigens. The model predicts that this type of vaccine will be most useful where the critical issue is the reduction in proportion of poor responders. PMID:17786221

Vaccination among Polish university students. Knowledge, beliefs and anti-vaccination attitudes.

PubMed

Zarobkiewicz, Michał Konrad; Zimecka, Aleksandra; Zuzak, Tomasz; Cieślak, Dominika; Roliński, Jacek; Grywalska, Ewelina

2017-11-02

Anti-vaccination movement has existed as long as the vaccines themselves, but its mode of action and social influences evolved over time. Such attitude with no doubt has negative impact on vaccination rates and eradication of infectious diseases. In this study, we used an online survey to examine vaccination attitudes of Polish university students of various degree and specialties. A total of 1,386 questionnaires were completed, among them 617 from students attending medical schools and 769 from students of non-medical schools. Up to 95.24% (N = 1320) of the study subjects, among them 98.70% and 92.46% of students of medical and non-medical specialties, respectively, declared willingness to vaccinate their children. 47.19% (N = 654) of participants have a contact with anti-vaccination propaganda at least once in a lifetimes. 42.64% (N = 591) of respondents were aware of the existence of anti-vaccination movements; 45.35% (N = 414) of participants, including 306 (51.52%) and 108 (33.86%) students of medical and non-medical disciplines, respectively, considered such movements as a negative phenomenon. Vaccination attitudes of students from medical and non-medical universities differed considerably. Vaccination knowledge and awareness among the students from non-medical universities were rather poor, markedly lower than in the students of medical disciplines. Nevertheless, irrespective of their major, Polish students have considerable knowledge gaps with regards to vaccination and need additional education in this matter.

An Outbreak of Measles in a University in Korea, 2014.

PubMed

Choe, Young June; Park, Young Joon; Kim, Ju Whi; Eom, Hye Eun; Park, Ok; Oh, Myoung Don; Lee, Jong Koo

2017-11-01

Measles has been declared eliminated from the Korea since 2006. In April 2014, a measles outbreak occurred at a University in Seoul. A total of 85 measles cases were identified. In order to estimate vaccine effectiveness of measles vaccine, we reviewed the vaccination records of the university students. The vaccine effectiveness of two doses of measles containing vaccine was 60.0% (95% CI, 38.2-74.1; P < 0.05). Transmission was interrupted after the introduction of outbreak-response immunization. The outbreak shows that pockets of under-immunity among college students may have facilitated the disease transmission despite the high 2-dose vaccination coverage in the community. © 2017 The Korean Academy of Medical Sciences.

Pros and cons of vaccination against serogroup B meningococcal disease.

PubMed

Delgado Rodríguez, Miguel; Domínguez García, Ángela

2018-02-09

A vaccine has recently been approved in the EU against meningococcal serogroup B, the main cause of meningococcal disease. There is a fierce debate about the decision regarding a universal vaccination in infants older than 2 months, as recommended by the majority of scientific societies. In western Europe the only country to have included the universal vaccination is the United Kingdom, with a lower incidence of the disease than Ireland. Other countries have also adopted it, such as the Czech Republic, Cuba and certain regions of Italy. Numerous cost-effectiveness studies have been published regarding the vaccination with different assumptions, which have supported the decision not to implant the universal vaccination because it exceeds the will to pay for a health benefit. We discuss the pros and cons of the universal vaccination against meningococcal B, recommended by the Sociedad Española de Pediatría (Spanish Society of Paediatrics), which as yet has not been implemented. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

[Influenza vaccination of hospital healthcare staff from the perspective of the employer: a positive balance].

PubMed

Hak, Eelko; Knol, Lisanne M; Wilschut, Jan C; Postma, Maarten J

2010-01-01

To assess the annual productivity loss among hospital healthcare workers attributable to influenza and to estimate the costs and economic benefits of a vaccination programme from the perspective of the the employer. Cost-benefit analysis. The percentage of work loss due to influenza was determined using monthly age and gender specific figures for productivity loss among healthcare workers of the University Medical Center Groningen (UMCG), the Netherlands over the period January 2006-June 2008. Influenza periods were determined on the basis of national surveillance data. The average increase in productivity loss in these periods was estimated by comparison with the periods outside influenza seasons. The direct costs of productivity loss from the perspective of the employer were estimated using the friction cost method. In the sensitivity analyses various modelling parameters were varied, such as the vaccination coverage. In the UMCG, with approximately 9,400 employees, the estimated annual costs associated with productivity loss due to influenza before the introduction of the yearly influenza vaccination program were € 675,242 or on average, € 72 per employee. The economic benefits of the current vaccination program with a vaccination coverage of 24% with a vaccine effectiveness of 71% were estimated at € 89,858 or € 10 per employee. The nett economic benefits of a vaccination program with a target vaccination coverage of 70% with a vaccine effectiveness of 71% were estimated at € 244,325 or € 26 per employee. This modelling study performed from the perspective of the employer showed that an annual influenza vaccination programme for hospital personnel can save costs.

High cost is the primary barrier reported by physicians who prescribe vaccines not included in India's Universal Immunization Program.

PubMed

Kahn, Geoffrey D; Thacker, Deep; Nimbalkar, Somashekhar; Santosham, Mathuram

2014-08-01

Haemophilus influenzae type B (Hib) vaccine, pneumococcal conjugate vaccine (PCV) and rotavirus (RV) vaccine are available in the private market in India, but, except for Hib in eight states, are not included in India's Universal Immunization Program (UIP). Pediatricians were surveyed about administering non-UIP vaccines. Most give these vaccines to some of their patients (73-83%, depending on vaccine), but few give them to all patients (7-18%). High cost was the most frequently cited barrier (93-96%). Only 10-12% of respondents had concerns about the efficacy of PCV or RV vaccine, and concerns about Hib vaccine efficacy or any vaccine safety issues were rare (1-3%). Practice varied by type of healthcare facility, with pediatricians at government hospitals least likely to administer non-UIP vaccines. Support for the inclusion of all three in the UIP was high (83-95%). Including Hib vaccine, PCV and RV vaccine in India's UIP would be supported by pediatricians and help eliminate the current barrier of high cost of these immunizations. © The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Knowledge and perceptions of polio and polio immunization in polio high-risk areas of Pakistan.

PubMed

Habib, Muhammad Atif; Soofi, Sajid Bashir; Ali, Noshad; Hussain, Imtiaz; Tabassum, Farhana; Suhag, Zamir; Anwar, Saeed; Ahmed, Imran; Bhutta, Zulfiqar Ahmed

2017-02-01

Pakistan and Afghanistan remain the only countries where polio is endemic, and Pakistan reports the most cases in the world. Although the rate is lower than in previous years, the situation remains alarming. We conducted a mixed methods study in high-risk areas of Pakistan to identify knowledge, attitudes, and practices of target populations about polio vaccine and its eradication, and to estimate coverage of routine immunization and oral polio vaccine. We surveyed 10,685 households in Karachi, 2522 in Pishin, and 2005 in Bajaur. Some knowledge of polio is universal, but important misconceptions persist. The findings of this study carry strategic importance for program direction and implementation.

Human papillomavirus vaccine awareness, acceptability, and decision-making factors among Chinese college students.

PubMed

Wang, Shao-Ming; Zhang, Shao-Kai; Pan, Xiong-Fei; Ren, Ze-Fang; Yang, Chun-Xia; Wang, Zeng-Zhen; Gao, Xiao-Hong; Li, Man; Zheng, Quan-Qing; Ma, Wei; Zhao, Fang-Hui; Qiao, You-Lin; Sivasubramaniam, Priya

2014-01-01

College students are recommended as the target groups for catch-up human papillomavirus (HPV) vaccination. Systematical exploration of awareness, acceptability, and decision-making factors of HPV vaccination among Chinese college students has been limited. A multi-center survey was conducted in mainland China between November 2011 and May 2012. College students aged 18-22 years were stratified by their grade, gender, and major for sampling. Socio-demographic and HPV-related information such as knowledge, perceptions, acceptability, and attitudes were collected through a questionnaire. A total of 3,497 undergraduates completed the questionnaire, among which 1,686 were males. The acceptability of the HPV vaccine was high (70.8%). Undergraduates from high-level universities, at lower grade, or with greater prior knowledge of HPV vaccines showed higher acceptability of HPV vaccination (ptrend <0.001). Additionally, undergraduates with vaccination experience outside the National Expanded Program on Immunization (OR=1.29; 95%CI: 1.10-1.51) or fear of HPV-related diseases (OR=2.79; 95%CI: 2.28-3.41) were more willing to accept HPV vaccination. General knowledge of HPV vaccine was low among undergraduates, and safety was a major concern (71.05%). The majority of students wished to pay less than 300RMB for HPV vaccine and chose the Chinese Center for Disease Control and Prevention as the most appropriate venue for vaccination. Although most undergraduates demonstrate positive attitudes towards HPV vaccination, challenges pertaining to introduction exist in China. Corresponding proactive education and governmental subsidy to do so are urgently needed by this age-group population. Suggestions and potential strategies indicated may help shape the future HPV vaccination program in China.

Geospatial patterns in influenza vaccination: evidence from uninsured and publicly insured children in North Carolina.

PubMed

Trogdon, Justin G; Ahn, Thomas

2015-03-01

The purpose of this study was to explore geospatial patterns in influenza vaccination. We conducted an ecological analysis of publicly funded influenza vaccinations at the ZIP code tabulation area (ZCTA) level using secondary data for publicly funded influenza vaccinations among eligible school-aged children (age range, 5-17 years) for the 2010-2011 and 2011-2012 influenza seasons from the North Carolina Immunization Registry (NCIR). NCIR data were merged by ZCTA with other publicly available data. We tested for spatial autocorrelation in unadjusted influenza vaccination rates using choropleth maps and Moran's I. We estimated nonspatial and spatial negative binomial models with spatially correlated random effects adjusted for demographic, economic, and health care variables. The study was conducted at the University of North Carolina at Chapel Hill in the spring of 2014. The NCIR demonstrated spatial autocorrelation in publicly funded influenza vaccinations among uninsured and means-tested, publicly insured school-aged children; ZCTAs tended to have influenza vaccination rates that were similar to their neighbors. This result was partially explained by included ZCTA characteristics, but not wholly. To the extent that the geospatial clustering of vaccination rates is the result of social influences, targeting interventions to increase influenza vaccination among school-aged children in one area could also lead to increases in neighboring areas. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Evaluating human papillomavirus vaccination programs in Canada: should provincial healthcare pay for voluntary adult vaccination?

PubMed

Llamazares, Marco; Smith, Robert J

2008-04-10

Recently, provincial health programs in Canada and elsewhere have begun rolling out vaccination against human papillomavirus for girls aged 9-13. While vaccination is voluntary, the cost of vaccination is waived, to encourage parents to have their daughters vaccinated. Adult women who are eligible for the vaccine may still receive it, but at a cost of approximately CAN$400. Given the high efficacy and immunogenicity of the vaccine, the possibility of eradicating targeted types of the virus may be feasible, assuming the vaccination programs are undertaken strategically. We develop a mathematical model to describe the epidemiology of vaccination against human papillomavirus, accounting for a widespread childhood vaccination program that may be supplemented by voluntary adult vaccination. A stability analysis is performed to determine the stability of the disease-free equilibrium. The critical vaccine efficacy and immunogenicity thresholds are derived, and the minimum level of adult vaccination required for eradication of targeted types is determined. We demonstrate that eradication of targeted types is indeed feasible, although the burden of coverage for a childhood-only vaccination program may be high. However, if a small, but non-negligible, proportion of eligible adults can be vaccinated, then the possibility of eradication of targeted types becomes much more favourable. We provide a threshold for eradication in general communities and illustrate the results with numerical simulations. We also investigate the effects of suboptimal efficacy and immunogenicity and show that there is a critical efficacy below which eradication of targeted types is not possible. If eradication is possible, then there is a critical immunogenicity such that even 100% childhood vaccination will not eradicate the targeted types of the virus and must be supplemented with voluntary adult vaccination. However, the level of adult vaccination coverage required is modest and may be achieved simply by removing the cost burden to vaccination. We recommend that provincial healthcare programs should pay for voluntary adult vaccination for women aged 14-26. However, it should be noted that our model results are preliminary, in that we have made a number of simplifying assumptions, including a lack of age-dependency in sexual partner rates, a lack of sexual activity outside of the vaccine age-range among females and a uniform age of sexual debut; thus, further work is desired to enhance the external generalisability of our results.

The effectiveness of measles-mumps-rubella (MMR) vaccination in the prevention of pediatric hospitalizations for targeted and untargeted infections: A retrospective cohort study.

PubMed

La Torre, Giuseppe; Saulle, Rosella; Unim, Brigid; Meggiolaro, Angela; Barbato, Angelo; Mannocci, Alice; Spadea, Antonietta

2017-08-03

To evaluate the effectiveness of the measles-mumps-rubella (MMR) vaccine in reducing hospitalizations for infectious disease, targeted and not targeted, as well as from respiratory diseases in children in Rome. The cohort was recomposed through record linkage of 2 archives (vaccination register and hospital discharge records. The analysis included 11,004 children. 20.9% did not receive the MMR vaccination, 49% and 30.1% received one and 2 doses. There were no hospitalizations for rubella, 2 for mumps, and 12 for measles. The vaccine was highly protective against measles and mumps hospitalizations (HR = 0.10; 95% CI: 0.03.0.34). Regarding all infectious diseases there were 414 hospitalizations, and the vaccine was protective (HR = 0.29; 95% CI: 0.25 to 0.34). Concerning respiratory diseases, there were 809 admissions (7.4%), and the vaccine was highly protective (HR: 0.18; 95% CI: 0.07 to 0.48). MMR vaccination is effective for the primary prevention of target and not targeted infectious diseases and may also limit hospitalizations for respiratory diseases.

Lymphatic-targeted cationic liposomes: a robust vaccine adjuvant for promoting long-term immunological memory.

PubMed

Wang, Ce; Liu, Peng; Zhuang, Yan; Li, Ping; Jiang, Boling; Pan, Hong; Liu, Lanlan; Cai, Lintao; Ma, Yifan

2014-09-22

Although retaining antigens at the injection site (the so-called "depot effect") is an important strategy for vaccine development, increasing evidence showed that lymphatic-targeted vaccine delivery with liposomes could be a promising approach for improving vaccine efficacy. However, it remains unclear whether antigen depot or lymphatic targeting would benefit long-term immunological memory, a major determinant of vaccine efficacy. In the present study, OVA antigen was encapsulated with DOTAP cationic liposomes (LP) or DOTAP-PEG-mannose liposomes (LP-Man) to generate depot or lymphatic-targeted liposome vaccines, respectively. The result of in vivo imaging showed that LP mostly accumulated near the injection site, whereas LP-Man not only effectively accumulated in draining lymph nodes (LNs) and the spleen, but also enhanced the uptake by resident antigen-presenting cells. Although LP vaccines with depot effect induced anti-OVA IgG more potently than LP-Man vaccines did on day 40 after priming, they failed to mount an effective B-cell memory response upon OVA re-challenge after three months. In contrast, lymphatic-targeted LP-Man vaccines elicited sustained antibody production and robust recall responses three months after priming, suggesting lymphatic targeting rather than antigen depot promoted the establishment of long-term memory responses. The enhanced long-term immunological memory by LP-Man was attributed to vigorous germinal center responses as well as increased Tfh cells and central memory CD4(+) T cells in the secondary lymphoid organs. Hence, lymphatic-targeted vaccine delivery with LP-Man could be an effective strategy to promote long-lasting immunological memory. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pharmacoeconomic spotlight on rotavirus vaccine RIX4414 (Rotarix™) in developed countries.

PubMed

Plosker, Greg L

2012-12-01

The most common cause of severe diarrhea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use, and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated 'real-world' effectiveness after the introduction of widespread rotavirus vaccination programs in the community setting. Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination program using RIX4414 was compared with no universal rotavirus vaccination program. There was a high degree of variability in base-case results across studies even when the studies were conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination program with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favorable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination program, results were generally sensitive to vaccine costs. Actual tender prices of a full vaccination course for each vaccine were not known at the time of the analyses and therefore had to be estimated.

A Research Agenda for Malaria Eradication: Vaccines

PubMed Central

2011-01-01

Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of “vaccines that interrupt malaria transmission” (VIMT), which includes not only “classical” transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented. PMID:21311586

A research agenda for malaria eradication: vaccines.

PubMed

2011-01-25

Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of "vaccines that interrupt malaria transmission" (VIMT), which includes not only "classical" transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented.

Vaccination among Polish university students. Knowledge, beliefs and anti-vaccination attitudes

PubMed Central

Zarobkiewicz, Michał Konrad; Zimecka, Aleksandra; Zuzak, Tomasz; Cieślak, Dominika; Roliński, Jacek; Grywalska, Ewelina

2017-01-01

ABSTRACT Anti-vaccination movement has existed as long as the vaccines themselves, but its mode of action and social influences evolved over time. Such attitude with no doubt has negative impact on vaccination rates and eradication of infectious diseases. In this study, we used an online survey to examine vaccination attitudes of Polish university students of various degree and specialties. A total of 1,386 questionnaires were completed, among them 617 from students attending medical schools and 769 from students of non-medical schools. Up to 95.24% (N = 1320) of the study subjects, among them 98.70% and 92.46% of students of medical and non-medical specialties, respectively, declared willingness to vaccinate their children. 47.19% (N = 654) of participants have a contact with anti-vaccination propaganda at least once in a lifetimes. 42.64% (N = 591) of respondents were aware of the existence of anti-vaccination movements; 45.35% (N = 414) of participants, including 306 (51.52%) and 108 (33.86%) students of medical and non-medical disciplines, respectively, considered such movements as a negative phenomenon. Vaccination attitudes of students from medical and non-medical universities differed considerably. Vaccination knowledge and awareness among the students from non-medical universities were rather poor, markedly lower than in the students of medical disciplines. Nevertheless, irrespective of their major, Polish students have considerable knowledge gaps with regards to vaccination and need additional education in this matter. PMID:28933660

Governments, off-patent vaccines, smallpox and universal childhood vaccination.

PubMed

Music, Stanley

2010-01-22

WHO is now celebrating more than 30 years of freedom from smallpox. What was originally seen as a victory over an ancient scourge can now be viewed as an epidemiologically driven programme to overcome governmental inertia and under-achievement in delivering an off-patent vaccine. Though efforts are accelerating global vaccine use, a plea is made to push the world's governments to commit to universal childhood vaccination via a proposed new programme. The latter should begin by exploiting a long list of ever more affordable off-patent vaccines, vaccines that can virtually eliminate the bulk of the world's current vaccine-preventable disease burden.

Remarks spoken before the audience at the final conference plenary session, entitled: "Future directions," at the International Conference on Advances in AIDS Vaccine Development. Fourth annual meeting of the National Cooperative Vaccine Development Groups for AIDS.

PubMed

Nzila, N

1992-08-01

Nzilambi Nzila, Visiting Scientist at the Johns Hopkins University Center for Immunization Research, responds to frequently asked questions about AIDS vaccine clinical trials in Africa. Conference attendees had asked him if the thinks the time is right to begin AIDS vaccine clinical trials in Africa; if African populations and decision makers want to be involved in the trials; and if he thinks that Africans will be used as guinea pigs. Given the magnitude of the AIDS pandemic in Africa and the general population desire for effective responses, Nzila feels that clinical trials could commence. Yes, Africans want to be involved in the early phases of clinical trials to both share their experiences and reap the benefits of an effective and safe vaccine should one be developed. Large IEC campaigns will simply not suffice to stem the spread of HIV. Further, decision makers in Africa should be involved as early as possible to allow then time to recruit HIV-negative volunteers for trials. Finally, Nzila does not equate involvement in vaccine trials with laboratory test animal status, especially since the target population is aware of its participation.

Reaching Hard-to-Reach Individuals: Nonselective Versus Targeted Outbreak Response Vaccination for Measles

PubMed Central

Minetti, Andrea; Hurtado, Northan; Grais, Rebecca F.; Ferrari, Matthew

2014-01-01

Current mass vaccination campaigns in measles outbreak response are nonselective with respect to the immune status of individuals. However, the heterogeneity in immunity, due to previous vaccination coverage or infection, may lead to potential bias of such campaigns toward those with previous high access to vaccination and may result in a lower-than-expected effective impact. During the 2010 measles outbreak in Malawi, only 3 of the 8 districts where vaccination occurred achieved a measureable effective campaign impact (i.e., a reduction in measles cases in the targeted age groups greater than that observed in nonvaccinated districts). Simulation models suggest that selective campaigns targeting hard-to-reach individuals are of greater benefit, particularly in highly vaccinated populations, even for low target coverage and with late implementation. However, the choice between targeted and nonselective campaigns should be context specific, achieving a reasonable balance of feasibility, cost, and expected impact. In addition, it is critical to develop operational strategies to identify and target hard-to-reach individuals. PMID:24131555

Influences on university students' intention to receive recommended vaccines: a cross-sectional survey.

PubMed

Landowska, Kate; Waller, Jo; Bedford, Helen; Rockliffe, Lauren; Forster, Alice S

2017-07-21

To explore predictors of university students' intention to receive a recommended vaccine and the main sources of vaccine-related information accessed by university students. Participants were recruited from University College London (UK) in summer 2015. 177 university students participated. The majority of participants were female (58%), White (68%) and had no religion (58%). Participants were aged 18 to 42 (mean age=23.6). Primary outcome measures included vaccine attitude, perceived subjective norm, perceived behavioural control, perceived self-efficacy, past receipt of recommended childhood vaccines, perceived adverse reaction to past vaccination and needle fear. As a secondary outcome sources of vaccine-related information were assessed. Students classified as high intenders were more likely to have received all recommended childhood vaccines (OR 3.57; 95% CI 1.21 to 10.59; p=0.022), be less afraid of needles (OR 2.44; 95% CI 1.12 to 5.36; p=0.026) and to have lived in the UK until at least the age of 4 compared with those not living in the UK until at least the age of 4 (OR 0.39; 95% CI 0.18 to 0.83; p=0.015) and those who lived both in the UK and elsewhere (OR 0.42; 95% CI 0.04 to 4.06; p=0.424). The multivariable model explained 25.5% of variance in intention to receive a recommended vaccine. The internet was the most commonly reported source of vaccination information. Findings provide an indication of the factors that may need to be addressed by interventions aiming to increase uptake of recommended vaccines in a university population. Future research is recommended using a prospective cohort design. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intradermal injection of an anti-Langerin-HIVGag fusion vaccine targets epidermal Langerhans cells in nonhuman primates and can be tracked in vivo.

PubMed

Salabert, Nina; Todorova, Biliana; Martinon, Frédéric; Boisgard, Raphaël; Zurawski, Gerard; Zurawski, Sandra; Dereuddre-Bosquet, Nathalie; Cosma, Antonio; Kortulewski, Thierry; Banchereau, Jacques; Levy, Yves; Le Grand, Roger; Chapon, Catherine

2016-03-01

The development of new immunization strategies requires a better understanding of early molecular and cellular events occurring at the site of injection. The skin is particularly rich in immune cells and represents an attractive site for vaccine administration. Here, we specifically targeted vaccine antigens to epidermal Langerhans cells (LCs) using a fusion protein composed of HIV antigens and a monoclonal antibody targeting Langerin. We developed a fluorescence imaging approach to visualize, in vivo, the vaccine-targeted cells. Studies were performed in nonhuman primates (NHPs) because of their relevance as a model to assess human vaccines. We directly demonstrated that in NHPs, intradermally injected anti-Langerin-HIVGag specifically targets epidermal LCs and induces rapid changes in the LC network, including LC activation and migration out of the epidermis. Vaccine targeting of LCs significantly improved anti-HIV immune response without requirement of an adjuvant. Although the co-injection of the TLR-7/8 synthetic ligand, R-848 (resiquimod), with the vaccine, did not enhance significantly the antibody response, it stimulated recruitment of HLA-DR+ inflammatory cells to the site of immunization. This study allowed us to characterize the dynamics of early local events following the injection of a vaccine-targeted epidermal LCs and R-848. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Knowledge, attitudes, beliefs, and behaviors of parents and healthcare providers before and after implementation of a universal rotavirus vaccination program.

PubMed

MacDougall, Donna M; Halperin, Beth A; Langley, Joanne M; MacKinnon-Cameron, Donna; Li, Li; Halperin, Scott A

2016-01-27

In Canada, rotavirus vaccine is recommended for all infants, but not all provinces/territories have publicly funded programs. We compared public and healthcare provider (HCP) knowledge, attitudes, beliefs, and behaviors in a province with a public health nurse-delivered, publicly funded rotavirus vaccination program to a province with a publicly funded, physician-delivered program. A third province with no vaccination program acted as a control. Information about knowledge, attitudes, beliefs, and behaviors of parents whose children were eligible for the universal program and healthcare providers responsible for administering the vaccine were collected through the use of two validated surveys distributed in public health clinics, physicians' offices, and via e-mail. Early and postvaccine-program survey results were compared. A total of 722 early implementation and 709 postimplementation parent surveys and 180 early and 141 postimplementation HCP surveys were analyzed. HCP and public attitudes toward rotavirus vaccination were generally positive and didn't change over time. More parents postprogram were aware of the NACI recommendation and the vaccination program and reported that their healthcare provider discussed rotavirus infection and vaccine with them. Prior to the program across all sites, more physicians than nurses were aware of the national recommendation regarding rotavirus vaccine. In the postprogram survey, however, more nurses were aware of the national recommendation and their provincial universal rotavirus vaccination program. Nurses had higher knowledge scores than physicians in the postprogram survey (p<0.001). Parents of young infants were also more knowledgeable about rotavirus and rotavirus vaccine in the two areas where universal programs were in place (p<0.001). Implementation of a universal rotavirus vaccination program was associated with an increase in knowledge and more positive attitudes toward rotavirus vaccine amongst parents of eligible infants. Nurses involved in a public health-delivered vaccination program were more knowledgeable and had more positive attitudes toward the vaccine than physicians in a jurisdiction where vaccine was physician-delivered. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal vaccination: moving the science forward

PubMed Central

Faucette, Azure N.; Unger, Benjamin L.; Gonik, Bernard; Chen, Kang

2015-01-01

BACKGROUND Infections remain one of the leading causes of morbidity in pregnant women and newborns, with vaccine-preventable infections contributing significantly to the burden of disease. In the past decade, maternal vaccination has emerged as a promising public health strategy to prevent and combat maternal, fetal and neonatal infections. Despite a number of universally recommended maternal vaccines, the development and evaluation of safe and effective maternal vaccines and their wide acceptance are hampered by the lack of thorough understanding of the efficacy and safety in the pregnant women and the offspring. METHODS An outline was synthesized based on the current status and major gaps in the knowledge of maternal vaccination. A systematic literature search in PUBMED was undertaken using the key words in each section title of the outline to retrieve articles relevant to pregnancy. Articles cited were selected based on relevance and quality. On the basis of the reviewed information, a perspective on the future directions of maternal vaccination research was formulated. RESULTS Maternal vaccination can generate active immune protection in the mother and elicit systemic immunoglobulin G (IgG) and mucosal IgG, IgA and IgM responses to confer neonatal protection. The maternal immune system undergoes significant modulation during pregnancy, which influences responsiveness to vaccines. Significant gaps exist in our knowledge of the efficacy and safety of maternal vaccines, and no maternal vaccines against a large number of old and emerging pathogens are available. Public acceptance of maternal vaccination has been low. CONCLUSIONS To tackle the scientific challenges of maternal vaccination and to provide the public with informed vaccination choices, scientists and clinicians in different disciplines must work closely and have a mechanistic understanding of the systemic, reproductive and mammary mucosal immune responses to vaccines. The use of animal models should be coupled with human studies in an iterative manner for maternal vaccine experimentation, evaluation and optimization. Systems biology approaches should be adopted to improve the speed, accuracy and safety of maternal vaccine targeting. PMID:25015234

Hepatitis B vaccination and changes in sexual risk behaviour among men who have sex with men in Amsterdam.

PubMed

Xiridou, M; Wallinga, J; Dukers-Muijers, N; Coutinho, R

2009-04-01

The impact of hepatitis B vaccination in men having sex with men in Amsterdam has been marginal until now, possibly because of increases in sexual risk behaviour counterbalancing the effect of vaccination. A mathematical model is used to describe the hepatitis B epidemic. The model shows that, with the current vaccination coverage, the decrease in incidence is small in the beginning. However, the number of infections prevented per vaccine administered rises over time. Nevertheless, increased risk behaviour reduces the benefit of vaccination. Targeting high-risk men is more successful in reducing and containing the epidemic than targeting low-risk men. In conclusion, the vaccination campaign is effective and should be intensified. High-risk men should be targeted for vaccination and for risk reduction.

Budget impact and cost-utility analysis of universal infant rotavirus vaccination in Spain.

PubMed

Imaz, Iñaki; Rubio, Beltrán; Cornejo, Ana M; González-Enríquez, Jesús

2014-04-01

Rotavirus is not included in the Spanish mass infant vaccination schedule but has also not been economically evaluated for its inclusion. We analysed cost-utility of the universal infant rotavirus vaccination using RotaTeq® versus no vaccination in Spain. We also carried out a budget impact analysis and determined the effect on results of different variables introduced in the model. A deterministic Markov model was built considering loss of quality of life for children and their parents, and introducing direct and indirect costs updated to 2011. The introduction of the vaccination using RotaTeq® as a universal infant vaccination would increase the annual health care budget in 10.43 million euro and would result in a gain of an additional Quality Adjusted Life Year at a cost of 280,338€ from the healthcare system perspective and 210,167€ from the societal perspective. The model was stable to variable modifications. To sum up, according to our model and estimates, the introduction of a universal infant rotavirus vaccination with RotaTeq® in Spain would cause a large impact on the health care budget and would not be efficient unless significant variations in vaccine price, vaccine efficacy and/or utilities took place. Copyright © 2013 Elsevier Inc. All rights reserved.

Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination

DTIC Science & Technology

2005-09-01

Std. Z39.18 Table of Contents C over ................................................................................................. S F 298...3. Rebbeck TR, Friebel R, Wagner R, Lynch HT, Garber JE, Daly MB, Isaacs C, Olopade 0, Neuhausen SL, Van’t Veer L, Eeles R, Evans F , Tomlinson G...counseling, testing and referral in North America. Chapter in Risk Assessment and Management in Cancer Genetics. Eds. Lalloo F , Kerr B, Friedman JM, Evans

Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination

DTIC Science & Technology

2007-09-01

TYPE OF REPORT: Annual Summary PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick...SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT...Fredericksen ZS, Stoppa-Lyonnet D, Coupier I, Hughes D, Hardouin A, Berthet P, Peock S, Cook M, Baynes C, Hodgson S, Morrison PJ, Porteous ME

Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination

DTIC Science & Technology

2008-09-01

Factors Determining Dissemination of Results and Uptake of Genetic Testing in Families with Known BRCA1/2 Mutations. Genetic Testing Vol. 12: 81-91, 2008...risk-reducing salpingo-oophorectomy, in press Familial Cancer, 2008 19. Schwartz GF, Hughes KS, Lynch HT, Fabian CJ, Fentiman IS, Robson ME...in high risk breast cancer families . In press. Cancer Research, 2008. Research Publications, peer-reviewed reviews, editorials and chapters: 1

Cost-effectiveness analysis of universal maternal immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in Brazil.

PubMed

Sartori, Ana Marli Christovam; de Soárez, Patrícia Coelho; Fernandes, Eder Gatti; Gryninger, Ligia Castellon Figueiredo; Viscondi, Juliana Yukari Kodaira; Novaes, Hillegonda Maria Dutilh

2016-03-18

Pertussis incidence has increased significantly in Brazil since 2011, despite high coverage of whole-cell pertussis containing vaccines in childhood. Infants <4 months are most affected. This study aimed to evaluate the cost-effectiveness of introducing universal maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) into the National Immunization Program in Brazil. Economic evaluation using a decision tree model comparing two strategies: (1) universal vaccination with one dose of Tdap in the third trimester of pregnancy and (2) current practice (no pertussis maternal vaccination), from the perspective of the health system and society. An annual cohort of newborns representing the number of vaccinated pregnant women were followed for one year. Vaccine efficacy were based on literature review. Epidemiological, healthcare resource utilization and cost estimates were based on local data retrieved from Brazilian Health Information Systems. Costs of epidemiological investigation and treatment of contacts of cases were included in the analysis. No discount rate was applied to costs and benefits, as the temporal horizon was one year. Primary outcome was cost per life year saved (LYS). Univariate and best- and worst-case scenarios sensitivity analysis were performed. Maternal vaccination of one annual cohort, with vaccine effectiveness of 78%, and vaccine cost of USD$12.39 per dose, would avoid 661 cases and 24 infant deaths of pertussis, save 1800 years of life and cost USD$28,942,808 and USD$29,002,947, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$15,608 and USD$15,590 per LYS, from the health system and societal perspective, respectively. In sensitivity analysis, the ICER was most sensitive to discounting of life years saved, variation in case-fatality, disease incidence, vaccine cost, and vaccine effectiveness. The results indicate that universal maternal immunization with Tdap is a cost-effective intervention for preventing pertussis cases and deaths in infants in Brazil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Negative attitude and low intention to vaccinate universally against varicella among public health professionals and parents in the Netherlands: two internet surveys.

PubMed

van Lier, Alies; Tostmann, Alma; Harmsen, Irene A; de Melker, Hester E; Hautvast, Jeannine L A; Ruijs, Wilhelmina L M

2016-03-15

Prior to introduction of universal varicella vaccination, it is crucial to gain insight into the willingness to vaccinate among the population. This is because suboptimal national vaccination coverage might increase the age of infection in children, which will lead to higher complication rates. We studied the attitude and intention to vaccinate against varicella among Dutch public health professionals who execute the National Immunisation Programme (NIP), and parents. Medical doctors and nurses of regional public health services (RPHS) and child health clinics (CHC), and a random sample of parents received an internet survey on varicella vaccination. Separate logistic regression models were used to identify determinants for a positive attitude (professionals) or a positive intention (parents) to vaccinate against varicella within the NIP (free of charge). The questionnaire was completed by 181 RPHS professionals (67%), 260 CHC professionals (46%), and 491 parents (33%). Of professionals, 21% had a positive attitude towards universal varicella vaccination, while 72% preferred to limit vaccination to high-risk groups only. Of parents, 28% had a positive intention to vaccinate their child against varicella within the NIP. The strongest determinant for a positive attitude or intention to vaccinate against varicella among professionals and parents was the belief that varicella is a disease serious enough to vaccinate against. We showed that a majority of the Dutch public health professionals and parents in this study have a negative attitude or low intention to vaccinate universally against varicella, as a result of the perceived low severity of the disease. Most participating professionals support selective vaccination to prevent varicella among high-risk groups.

US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines.

PubMed

Saraiya, Mona; Unger, Elizabeth R; Thompson, Trevor D; Lynch, Charles F; Hernandez, Brenda Y; Lyu, Christopher W; Steinau, Martin; Watson, Meg; Wilkinson, Edward J; Hopenhayn, Claudia; Copeland, Glenn; Cozen, Wendy; Peters, Edward S; Huang, Youjie; Saber, Maria Sibug; Altekruse, Sean; Goodman, Marc T

2015-06-01

This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Modeling Preventative Strategies against HPV-Related Disease in Developed Countries

PubMed Central

Canfell, Karen; Chesson, Harrell; Kulasingam, Shalini L.; Berkhof, Johannes; Diaz, Mireia; Kim, Jane J.

2013-01-01

Over the last five years, prophylactic vaccination against Human Papillomavirus (HPV) in pre-adolescent females has been introduced in most developed countries, supported by modeled evaluations which have almost universally found vaccination of pre-adolescent females to be cost-effective. Studies to date suggest that vaccination of pre-adolescent males may also be cost-effective at a cost per vaccinated individual ~US$400–500 if vaccination coverage in females cannot be increased above ~50%; but if it is possible, increasing coverage in females appears to be a better return on investment. Comparative evaluation of the quadrivalent (HPV16,18,6,11) and bivalent (HPV16,18) vaccines centers around the potential tradeoff between protection against anogenital warts and vaccine-specific levels of cross-protection against infections not targeted by the vaccines. Future evaluations will also need to consider the cost-effectiveness of a next generation nonavalent vaccine designed to protect against ~90% of cervical cancers. The timing of the effect of vaccination on cervical screening programs will be country-specific and will depend on vaccination catch-up age range and coverage and the age at which screening starts. Initial evaluations suggest that if screening remains unchanged it will be less cost-effective in vaccinated compared to unvaccinated women but, in the context of current vaccines, will remain an important prevention method. Comprehensive evaluation of new approaches to screening will need to consider the population-level effects of vaccination over time. New screening strategies of particular interest include delaying the start age of screening, increasing the screening interval and switching to primary HPV screening. Future evaluations of screening will also need to focus on the effects of disparities in screening and vaccination uptake, the potential effects of vaccination on screening participation, and the effects of imperfect compliance with screening recommendations. PMID:23199959

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries

PubMed Central

Knight, Gwenan M.; Griffiths, Ulla K.; Sumner, Tom; Laurence, Yoko V.; Gheorghe, Adrian; Vassall, Anna; Glaziou, Philippe; White, Richard G.

2014-01-01

To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40–80% efficacy, and to be targeted at “infants” or “adolescents/adults.” Vaccine prices were tiered by income group (US $1.50–$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024–2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11–24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42–1.58) million TB cases could be prevented at $1,692 ($634–$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle–, and upper-middle–income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies. PMID:25288770

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.

Immunization Strategies Targeting Newly Arrived Migrants in Non-EU Countries of the Mediterranean Basin and Black Sea

PubMed Central

Giambi, Cristina; Del Manso, Martina; Dente, Maria Grazia; Napoli, Christian; Montaño-Remacha, Carmen; Riccardo, Flavia; Declich, Silvia

2017-01-01

Background: The World Health Organization recommends that host countries ensure appropriate vaccinations to refugees, asylum seekers and migrants. However, information on vaccination strategies targeting migrants in host countries is limited. Methods: In 2015–2016 we carried out a survey among national experts from governmental bodies of 15 non-EU countries of the Mediterranean and Black Sea in order to document and share national vaccination strategies targeting newly arrived migrants. Results: Four countries reported having regulations/procedures supporting the immunization of migrants at national level, one at sub-national level and three only targeting specific population groups. Eight countries offer migrant children all the vaccinations included in their national immunization schedule; three provide only selected vaccinations, mainly measles and polio vaccines. Ten and eight countries also offer selected vaccinations to adolescents and adults respectively. Eight countries provide vaccinations at the community level; seven give priority vaccines in holding centres or at entry sites. Data on administered vaccines are recorded in immunization registries in nine countries. Conclusions: Although differing among countries, indications for immunizing migrants are in place in most of them. However, we cannot infer from our findings whether those strategies are currently functioning and whether barriers to their implementation are being faced. Further studies focusing on these aspects are needed to develop concrete and targeted recommendations for action. Since migrants are moving across countries, development of on-line registries and cooperation between countries could allow keeping track of administered vaccines in order to appropriately plan immunization series and avoid unnecessary vaccinations. PMID:28441361

Immunization Strategies Targeting Newly Arrived Migrants in Non-EU Countries of the Mediterranean Basin and Black Sea.

PubMed

Giambi, Cristina; Del Manso, Martina; Dente, Maria Grazia; Napoli, Christian; Montaño-Remacha, Carmen; Riccardo, Flavia; Declich, Silvia; Network For The Control Of Cross-Border Health Threats In The Mediterranean Basin And Black Sea For The ProVacMed Project

2017-04-25

Background : The World Health Organization recommends that host countries ensure appropriate vaccinations to refugees, asylum seekers and migrants. However, information on vaccination strategies targeting migrants in host countries is limited. Methods : In 2015-2016 we carried out a survey among national experts from governmental bodies of 15 non-EU countries of the Mediterranean and Black Sea in order to document and share national vaccination strategies targeting newly arrived migrants. Results : Four countries reported having regulations/procedures supporting the immunization of migrants at national level, one at sub-national level and three only targeting specific population groups. Eight countries offer migrant children all the vaccinations included in their national immunization schedule; three provide only selected vaccinations, mainly measles and polio vaccines. Ten and eight countries also offer selected vaccinations to adolescents and adults respectively. Eight countries provide vaccinations at the community level; seven give priority vaccines in holding centres or at entry sites. Data on administered vaccines are recorded in immunization registries in nine countries. Conclusions : Although differing among countries, indications for immunizing migrants are in place in most of them. However, we cannot infer from our findings whether those strategies are currently functioning and whether barriers to their implementation are being faced. Further studies focusing on these aspects are needed to develop concrete and targeted recommendations for action. Since migrants are moving across countries, development of on-line registries and cooperation between countries could allow keeping track of administered vaccines in order to appropriately plan immunization series and avoid unnecessary vaccinations.

Considerations around the introduction of a cholera vaccine in Bangladesh.

PubMed

Nelson, Christopher B; Mogasale, Vittal; Bari, Tajul Islam A; Clemens, John D

2014-12-12

Cholera is an endemic and epidemic disease in Bangladesh. On 3 March 2013, a meeting on cholera and cholera vaccination in Bangladesh was convened by the Foundation Mérieux jointly with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B). The purpose of the meeting was to discuss the investment case for cholera vaccination as a complimentary control and prevention strategy. The performance of a new low cost oral cholera vaccine, Shanchol™, used in recent trials in Bangladesh, was also reviewed in the context of a potential large-scale public-sector vaccination program. Findings showed the oral vaccine to be highly cost-effective when targeting ages 1-14 y, and cost-effective when targeting ages 1+y, in high-burden/high-risk districts. Other vaccination strategies targeting urban slums and rural areas without improved water were found to be cost-effective. Regardless of cost-effectiveness (value), the budget impact (affordability) will be an important determinant of which target population and vaccination strategy is selected. Most importantly, adequate vaccine supply for the proposed vaccination programs must be addressed in the context of global efforts to establish a cholera vaccine stockpile and supply other control and prevention efforts. Copyright © 2014. Published by Elsevier Ltd.. All rights reserved.

Knowledge, attitude, and uptake related to human papillomavirus vaccination among young women in Germany recruited via a social media site.

PubMed

Remschmidt, Cornelius; Walter, Dietmar; Schmich, Patrick; Wetzstein, Matthias; Deleré, Yvonne; Wichmann, Ole

2014-01-01

Many industrialized countries have introduced human papillomavirus (HPV) vaccination of young women, but vaccine uptake often remains suboptimal. This study aimed to investigate whether a social media site like Facebook is an appropriate tool to assess knowledge, attitude and uptake related to HPV vaccination in young women in Germany. Between December 2012 and January 2013 two different targeting strategies were implemented on Facebook, providing a link to an online questionnaire. Advertisements were displayed to female Facebook users aged 18-25 years living in Germany. During the simple targeting strategy, advertisements comprised health-related images along with various short titles and text messages. During the focused strategy, advertisements were targeted to users who in addition had certain fashion brands or pop stars listed on their profiles. The targeting strategies were compared with respect to participant characteristics. Univariate and multivariate analyses were used to identify factors associated with HPV vaccine uptake. A total of 1161 women participated. The two targeting strategies resulted in significant differences regarding educational status and migrant background. Overall, awareness of HPV was high, but only 53% received at least one vaccine dose. In multivariate analysis, HPV vaccine uptake was independently associated with a physician's recommendation and trust in vaccine effectiveness. Concerns of adverse effects were negatively associated with vaccine uptake. Social network recruitment permits fast and convenient access to young people. Sample characteristics can be manipulated by adjusting targeting strategies. There is further need for promoting knowledge of HPV vaccination among young women. Physicians have a major role in the vaccination decision-making process of young women.

Knowledge, attitude, and uptake related to human papillomavirus vaccination among young women in Germany recruited via a social media site

PubMed Central

Remschmidt, Cornelius; Walter, Dietmar; Schmich, Patrick; Wetzstein, Matthias; Deleré, Yvonne; Wichmann, Ole

2014-01-01

Background: Many industrialized countries have introduced human papillomavirus (HPV) vaccination of young women, but vaccine uptake often remains suboptimal. This study aimed to investigate whether a social media site like Facebook is an appropriate tool to assess knowledge, attitude and uptake related to HPV vaccination in young women in Germany. Methods: Between December 2012 and January 2013 two different targeting strategies were implemented on Facebook, providing a link to an online questionnaire. Advertisements were displayed to female Facebook users aged 18–25 years living in Germany. During the simple targeting strategy, advertisements comprised health-related images along with various short titles and text messages. During the focused strategy, advertisements were targeted to users who in addition had certain fashion brands or pop stars listed on their profiles. The targeting strategies were compared with respect to participant characteristics. Univariate and multivariate analyses were used to identify factors associated with HPV vaccine uptake. Results: A total of 1161 women participated. The two targeting strategies resulted in significant differences regarding educational status and migrant background. Overall, awareness of HPV was high, but only 53% received at least one vaccine dose. In multivariate analysis, HPV vaccine uptake was independently associated with a physician's recommendation and trust in vaccine effectiveness. Concerns of adverse effects were negatively associated with vaccine uptake. Discussion: Social network recruitment permits fast and convenient access to young people. Sample characteristics can be manipulated by adjusting targeting strategies. There is further need for promoting knowledge of HPV vaccination among young women. Physicians have a major role in the vaccination decision-making process of young women. PMID:25483492

Awareness and acceptance of human papillomavirus vaccination among health sciences students in Malaysia.

PubMed

Rajiah, Kingston; Maharajan, Mari Kannan; Chin, Nang Sue; Num, Kelly Sze Fang

2015-12-01

The major cause of cervical cancer is human papillomavirus (HPV) for which vaccination is available. The success HPV vaccination programme largely depend on the degree of knowledge of the healthcare providers who can recommend to the public. Health sciences students as future healthcare providers play a major role in HPV vaccination initiatives. The objective of this study was to evaluate the knowledge, attitude, practice and to find out the willingness to pay for HPV vaccination among the health sciences students in a private university. The cross-sectional study was conducted among the university students studying health sciences program using a validated questionnaire to measure their awareness and acceptance of HPV vaccination. The students demonstrated moderate knowledge about HPV infection and vaccination with mean knowledge scores of 9.3 out of 17. Students were showing positive attitude towards HPV vaccination with mean scores of 3.80 out of 5. However, low HPV vaccination uptake rate was reported among the students. Most of the students were willing to recommend HPV vaccine. The participants felt that the cost is the major barrier towards HPV vaccination and they felt the government should cover the cost of vaccination for all. The results of this study may be helpful in establishing educational policies on cervical cancer-related topics in the universities.

Protection of medical and paramedical university students in Lebanon against measles, mumps, rubella and varicella: active measures are needed.

PubMed

Chamat, Soulaima; Salameh, Pascale; Haddad, Nabil; Berry, Atika; Chedid, Philippe; Bouharoun-Tayoun, Hasnaa

2011-08-01

In many countries, universities require students to either show a physician-certified proof of immunity or to get vaccinated against measles, mumps, rubella and varicella, prior to their registration in medical and paramedical majors. The objective of this study was to evaluate the need to implement this policy in Lebanon. A cross-sectional study was performed on students of the Lebanese University (LU), faculties of Medicine, Dentistry, Pharmacy and Public Health. The serological immunity status was assessed by determining specific antibody titer and the disease and vaccination history of 502 students was collected. Based on percentages of susceptibility, a cost-effectiveness analysis was performed to compare systematic vaccination without prior serological testing with selective vaccination of seronegative students. Percentages of individuals with serologically confirmed immunity against varicella, measles, rubella and mumps were 93%, 86%, 88% and 75% respectively, and 42% of the students were susceptible to at least one of the pathogens covered by the MMR vaccine. Compilation of 186 vaccination records indicated that only 19 students (10%) had been adequately vaccinated. Moreover, among those, 7 students (37%) were still unprotected against at least one virus. Systematic vaccination against MMR was found to be 4-5 times less expensive than selective vaccination, while selective vaccination of seronegative individuals was more cost-efficient for varicella. Since, in this population, very few individuals were able to present a proof of adequate vaccination, it is recommended to systematically vaccinate healthcare students in Lebanon against MMR. For varicella, selective vaccination after serological testing should be performed. Copyright © 2011 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Barriers to pandemic influenza vaccination and uptake of seasonal influenza vaccine in the post-pandemic season in Germany.

PubMed

Böhmer, Merle M; Walter, Dietmar; Falkenhorst, Gerhard; Müters, Stephan; Krause, Gérard; Wichmann, Ole

2012-10-31

In Germany, annual vaccination against seasonal influenza is recommended for certain target groups (e.g. persons aged ≥60 years, chronically ill persons, healthcare workers (HCW)). In season 2009/10, vaccination against pandemic influenza A(H1N1)pdm09, which was controversially discussed in the public, was recommended for the whole population. The objectives of this study were to assess vaccination coverage for seasonal (seasons 2008/09-2010/11) and pandemic influenza (season 2009/10), to identify predictors of and barriers to pandemic vaccine uptake and whether the controversial discussions on pandemic vaccination has had a negative impact on seasonal influenza vaccine uptake in Germany. We analysed data from the 'German Health Update' (GEDA10) telephone survey (n=22,050) and a smaller GEDA10-follow-up survey (n=2,493), which were both representative of the general population aged ≥18 years living in Germany. Overall only 8.8% of the adult population in Germany received a vaccination against pandemic influenza. High socioeconomic status, having received a seasonal influenza shot in the previous season, and belonging to a target group for seasonal influenza vaccination were independently associated with the uptake of pandemic vaccines. The main reasons for not receiving a pandemic vaccination were 'fear of side effects' and the opinion that 'vaccination was not necessary'. Seasonal influenza vaccine uptake in the pre-pandemic season 2008/09 was 52.8% among persons aged ≥60 years; 30.5% among HCW, and 43.3% among chronically ill persons. A decrease in vaccination coverage was observed across all target groups in the first post-pandemic season 2010/11 (50.6%, 25.8%, and 41.0% vaccination coverage, respectively). Seasonal influenza vaccination coverage in Germany remains in all target groups below 75%, which is a declared goal of the European Union. Our results suggest that controversial public discussions about safety and the benefits of pandemic influenza vaccination may have contributed to both a very low uptake of pandemic vaccines and a decreased uptake of seasonal influenza vaccines in the first post-pandemic season. In the upcoming years, the uptake of seasonal influenza vaccines should be carefully monitored in all target groups to identify if this trend continues and to guide public health authorities in developing more effective vaccination and communication strategies for seasonal influenza vaccination.

Comparison of two vaccination strategies against hepatitis A and B in patients with chronic hepatitis C.

PubMed

Díez Redondo, M P; Almaraz, A; Jiménez Rodríguez-Vila, M; Santamaría, A; de Castro, J; Torrego, J C; Caro-Patón, A

2009-04-01

although the vaccination against hepatitis A (VAH) and hepatitis B (VBH) is recommended in patients with HCV, the most cost-effective strategy has not been established. Our objective was to compare the cost-effectiveness of universal strategy (vaccination all patients) with selective strategy (vaccination only patients against virus they lack immunity to) in patients with HCV. we compared the direct medical costs of the two vaccination strategies against both viruses in 313 patients with HC. Serological markers for HAV (anti-HAV) and HBV (HbsAg, anti HBs, anti HBc) were determined in the 313 patients and the costs of the vaccines and the blood tests necessary to determinate the immunity state in our care system were considered. the prevalence of anti-HAV was 81,2% and of anti-HBc was 24,6%. The prevalence of anti-HAV increases with age. HAV vaccination with universal strategy has a cost of 19.806,64 euro and with selective one of 9.899,62 euro. HBV vaccination with universal strategy rose to 18.780 euro and to 20.385,57 euro with selective one (employing anti-HBc). Costs were analysed in different groups of age and several hepatitis HBV risk factors. the selective vaccination strategy against HAV was most cost-effective in our patients with HCV. However, when the prevalence of the anti-HAV decreased to less than 20% universal strategy will be the best option. Difference of cost-effective between the two vaccination strategies against HBV was small, on behalf of universal one, so in groups with higher anti-HBc prevalence, like parenteral drugs users and tattoos, the selective strategy could be the best option.

Considerations on the Current Universal Vaccination Policy against Hepatitis A in Greece after Recent Outbreaks

PubMed Central

Mellou, Kassiani; Sideroglou, Theologia; Papaevangelou, Vassiliki; Katsiaflaka, Anna; Bitsolas, Nikolaos; Verykouki, Eleni; Triantafillou, Eleni; Baka, Agoritsa; Georgakopoulou, Theano; Hadjichristodoulou, Christos

2015-01-01

Greece is the only European Union member state that in 2008 included hepatitis A (HAV) vaccine in the routine national childhood immunization program (NCIP). Given that the resources allocated to public health have dramatically decreased since 2008 and that Greece is a low endemicity country for the disease, the benefit from universal vaccination has been questioned. The aim of this paper is to summarize the available epidemiological data of the disease for 1982-2013, and discuss the effects of universal vaccination on disease morbidity. Descriptive analysis, ARIMA modeling and time series intervention analysis were conducted using surveillance data of acute HAV. A decreasing trend of HAV notification rate over the years was identified (p<0.001). However, universal vaccination (~ 80% vaccine coverage of children) had no significant effect on the annual number of reported cases (p = 0.261) and has resulted to a progressive increase of the average age of infection in the general population. The mean age of cases before the inclusion of the vaccine to NCIP (24.1 years, SD = 1.5) was significantly lower than the mean age of cases after 2008 (31.7 years, SD = 2.1) (p<0.001). In the last decade, one third of all reported cases were Roma (a population accounting for 1.5% of the country’s total population) and in 2013 three outbreaks with 16, 9 and 25 Roma cases respectively, were recorded, indicating the decreased effectiveness of the current immunization strategy in this group. Data suggest that universal vaccination may need to be re-considered. Probably a more cost effective approach would be to implement a program that will include: a) vaccination of high risk groups, b) universal vaccination of Roma children and improving conditions at Roma camps, c) education of the population and travel advice, and d) enhancement of the control measures to increase safety of shellfish and other foods. PMID:25590132

Considerations on the current universal vaccination policy against hepatitis A in Greece after recent outbreaks.

PubMed

Mellou, Kassiani; Sideroglou, Theologia; Papaevangelou, Vassiliki; Katsiaflaka, Anna; Bitsolas, Nikolaos; Verykouki, Eleni; Triantafillou, Eleni; Baka, Agoritsa; Georgakopoulou, Theano; Hadjichristodoulou, Christos

2015-01-01

Greece is the only European Union member state that in 2008 included hepatitis A (HAV) vaccine in the routine national childhood immunization program (NCIP). Given that the resources allocated to public health have dramatically decreased since 2008 and that Greece is a low endemicity country for the disease, the benefit from universal vaccination has been questioned. The aim of this paper is to summarize the available epidemiological data of the disease for 1982-2013, and discuss the effects of universal vaccination on disease morbidity. Descriptive analysis, ARIMA modeling and time series intervention analysis were conducted using surveillance data of acute HAV. A decreasing trend of HAV notification rate over the years was identified (p<0.001). However, universal vaccination (~ 80% vaccine coverage of children) had no significant effect on the annual number of reported cases (p = 0.261) and has resulted to a progressive increase of the average age of infection in the general population. The mean age of cases before the inclusion of the vaccine to NCIP (24.1 years, SD = 1.5) was significantly lower than the mean age of cases after 2008 (31.7 years, SD = 2.1) (p<0.001). In the last decade, one third of all reported cases were Roma (a population accounting for 1.5% of the country's total population) and in 2013 three outbreaks with 16, 9 and 25 Roma cases respectively, were recorded, indicating the decreased effectiveness of the current immunization strategy in this group. Data suggest that universal vaccination may need to be re-considered. Probably a more cost effective approach would be to implement a program that will include: a) vaccination of high risk groups, b) universal vaccination of Roma children and improving conditions at Roma camps, c) education of the population and travel advice, and d) enhancement of the control measures to increase safety of shellfish and other foods.

A qualitative analysis of the beliefs of Japanese anti-influenza vaccination website authors.

PubMed

Okuhara, Tsuyoshi; Ishikawa, Hirono; Kato, Mio; Okada, Masafumi; Kiuchi, Takahiro

2018-04-01

Influenza vaccine coverage among the Japanese population is less than optimal. Anti-vaccination sentiment exists worldwide, and Japan is no exception. Anti-influenza vaccination activists argue on the internet that influenza vaccine has little or no efficacy and a high risk of side effects, and they warn that people should forgo vaccination. We conducted a qualitative analysis to explore beliefs underlying the messages of anti-influenza vaccination websites, by focusing on the perceived value these beliefs provide to those who hold them. We conducted online searches in January 2017 using two major Japanese search engines (Google Japan and Yahoo! Japan). Targeted websites were classified as "pro", "anti", or "neutral" depending on their claims. We applied a dual analytic approach-inductive thematic analysis and deductive interpretative analysis-to textual data of the anti websites. Of the 113 anti websites, we identified two themes that correspond to beliefs: it is necessary to 1) protect others against risks and exploitation related to influenza vaccination, and 2) educate others about hidden truths and self-determination. Authors of anti websites ascribed two values (people's "safety" and one's own "self-esteem") to their beliefs. Website authors may engage in anti-vaccination activities because they want to feel they are virtuous, saving people from harm caused by vaccination, and to boost their self-esteem, thinking "I am enlightening uninformed people." The anti-vaccination beliefs of website authors were considered to be strong. In promoting vaccination, it would be better not to target outright vaccine refusers, such as the authors of anti-vaccination websites; it is preferable to target vaccine-hesitant people who are more amenable to changing their attitudes toward vaccination. We discuss possible means of promoting vaccination in that target population.

Assessing university students' sexual risk behaviors as predictors of human papillomavirus (HPV) vaccine uptake behavior.

PubMed

Rohde, Rebecca L; Adjei Boakye, Eric; Christopher, Kara M; Geneus, Christian J; Walker, Ronald J; Varvares, Mark A; Osazuwa-Peters, Nosayaba

2018-06-14

There exists a significant gap in vaccine coverage of the human papillomavirus (HPV) among college-aged students. This study assessed sexual risk-taking behavior among university students and analyzed predictors of HPV vaccine initiation and completion in this population. Data (n = 746) were from an anonymous online, cross-sectional survey distributed to university students, between the ages of 19-26 years, at a private Midwestern university. Both chi-square and multivariable logistics regression models estimated the association between sociodemographic characteristics and sexual risk factors (including number of vaginal sexual partners, number of oral sexual partners, initiation of oral sex, and initiation of vaginal sex), with HPV vaccine initiation and completion. A significant number of participants (40%) had not received a single dose of the HPV vaccine series. Of those who initiated the series, more than half (51%) did not achieve completion. Additionally, a greater number of participants have had multiple (4 or more) oral sexual partners than vaginal sexual partners (25.7% vs. 20.3%). After adjusting for covariates, it was found that sexual risk factors were not significantly associated with HPV vaccine initiation or completion. HPV vaccine initiation and completion rates are suboptimal among university students. High levels of sexual-risk taking behaviors associated with HPV infection persist, yet are not significant predictors of HPV vaccine behaviors in this age group. To increase uptake among 18-26-year-old students, future public health interventions should focus on HPV vaccine education and uptake across the entire population, irrespective of sexual risk profile. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Influenza Virus Hemagglutinin Stalk-Specific Antibodies in Human Serum are a Surrogate Marker for In Vivo Protection in a Serum Transfer Mouse Challenge Model.

PubMed

Jacobsen, Henning; Rajendran, Madhusudan; Choi, Angela; Sjursen, Haakon; Brokstad, Karl A; Cox, Rebecca J; Palese, Peter; Krammer, Florian; Nachbagauer, Raffael

2017-09-19

The immunogenicity of current influenza virus vaccines is assessed by measuring an increase of influenza virus-specific antibodies in a hemagglutination inhibition assay. This method exclusively measures antibodies against the hemagglutinin head domain. While this domain is immunodominant, it has been shown that hemagglutination inhibition titers do not always accurately predict protection from disease. In addition, several novel influenza virus vaccines that are currently under development do not target the hemagglutinin head domain, but rather more conserved sites, including the hemagglutinin stalk. Importantly, antibodies against the hemagglutinin stalk do not show activity in hemagglutination inhibition assays and will require different methods for quantification. In this study, we tested human serum samples from a seasonal influenza virus vaccination trial and an avian H5N1 virus vaccination trial for antibody activities in multiple types of assays, including binding assays and also functional assays. We then performed serum transfer experiments in mice which then received an H1N1 virus challenge to assess the in vivo protective effects of the antibodies. We found that hemagglutinin-specific antibody levels measured in an enzyme-linked immunosorbent assay (ELISA) correlated well with protection from weight loss in mice. In addition, we found that weight loss was also inversely correlated with the level of serum antibody-dependent cellular cytotoxicity (ADCC) as measured in a reporter assay. These findings indicate that protection is in part conferred by Fc-dependent mechanisms. In conclusion, ELISAs can be used to measure hemagglutinin-specific antibody levels that could serve as a surrogate marker of protection for universal influenza virus vaccines. IMPORTANCE Influenza viruses are a serious concern for public health and cause a large number of deaths worldwide every year. Current influenza virus vaccines can confer protection from disease, but they often show low efficacy due to the ever-changing nature of the viruses. Novel vaccination approaches target conserved epitopes of the virus, including the hemagglutinin stalk domain, to elicit universally protective antibodies that also bind to mutated viruses or new subtypes of viruses. Importantly, the hemagglutination inhibition assay-the only assay that has been accepted as a correlate of protection by regulatory authorities-cannot measure antibodies against the hemagglutinin stalk domain. Therefore, novel correlates of protection and assays to measure vaccine immunogenicity need to be developed. In this study, we correlated the results from multiple assays with protection in mice after transfer of human serum and a lethal virus challenge to investigate potential novel serological surrogate markers for protection. Copyright © 2017 Jacobsen et al.

Generalized herd effects and vaccine evaluation: impact of live influenza vaccine on off-target bacterial colonisation.

PubMed

Mina, Michael J

2017-06-01

Interactions between pathogens and commensal microbes are major contributors to health and disease. Infectious diseases however are most often considered independent, viewed within a one-host one-pathogen paradigm and, by extension, the interventions used to treat and prevent them are measured and evaluated within this same paradigm. Vaccines, especially live vaccines, by stimulating immune responses or directly interacting with other microbes can alter the environment in which they act, with effects that span across pathogen species. Live attenuated infl uenza vaccines for example, while safe, increase upper respiratory tract bacterial carriage density of important human commensal pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Further, by altering the ecological niche and dynamics of phylogenetically distinct microbes within the host, vaccines may unintentionally affect transmission of non-vaccine targeted pathogens. Thus, vaccine effects may span across species and across scales, from the individual to the population level. In keeping with traditional vaccine herd-effects that indirectly protect even unvaccinated individuals by reducing population prevalence of vaccine-targeted pathogens, we call these cross-species cross-scale effects "generalized herd-effects". As opposed to traditional herd-effects, "generalized" relaxes the assumption that the effect occurs at the level of the vaccine-target pathogen and "herd effect" implies, as usual, that the effects indirectly impact the population at large, including unvaccinated bystanders. Unlike traditional herd-effects that decrease population prevalence of the vaccine-target, generalized herd-effects may decrease or increase prevalence and disease by the off-target pathogen. LAIV, for example, by increasing pneumococcal density in the upper respiratory tract of vaccine recipients, especially children, may increase pneumococcal transmission and prevalence, leading to excess pneumococcal invasive disease in the population, especially among the elderly and others most susceptible to pneumococcal disease. However, these effects may also be beneficial, for example the large reductions in all-cause mortality noted following measles vaccines. Here we discuss evidence for these novel vaccine effects and suggest that vaccine monitoring and evaluation programs should consider generalized herd effects to appreciate the full impacts of vaccines, beneficial or detrimental, across species and scales that are inevitably hiding in plain sight, affecting human health and disease. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Strategic priorities for respiratory syncytial virus (RSV) vaccine development

PubMed Central

Anderson, L.J.; Dormitzer, P.R.; Nokes, D.J.; Rappuoli, R.; Roca, A.; Graham, B.S.

2013-01-01

Although RSV has been a high priority for vaccine development, efforts to develop a safe and effective vaccine have yet to lead to a licensed product. Clinical and epidemiologic features of RSV disease suggest there are at least 4 distinct target populations for vaccines, the RSV naïve young infant, the RSV naïve child ≥6 months of age, pregnant women (to provide passive protection to newborns), and the elderly. These target populations raise different safety and efficacy concerns and may require different vaccination strategies. The highest priority target population is the RSV naïve child. The occurrence of serious adverse events associated with the first vaccine candidate for young children, formalin inactivated RSV (FI-RSV), has focused vaccine development for the young RSV naïve child on live virus vaccines. Enhanced disease is not a concern for persons previously primed by a live virus infection. A variety of live-attenuated viruses have been developed with none yet achieving licensure. New live-attenuated RSV vaccines are being developed and evaluated that maybe sufficiently safe and efficacious to move to licensure. A variety of subunit vaccines are being developed and evaluated primarily for adults in whom enhanced disease is not a concern. An attenuated parainfluenza virus 3 vector expressing the RSV F protein was evaluated in RSV naïve children. Most of these candidate vaccines have used the RSV F protein in various vaccine platforms including virus-like particles, nanoparticles, formulated with adjuvants, and expressed by DNA or virus vectors. The other surface glycoprotein, the G protein, has also been used in candidate vaccines. We now have tools to make and evaluate a wide range of promising vaccines. Costly clinical trials in the target population are needed to evaluate and select candidate vaccines for advancement to efficacy trials. Better data on RSV-associated mortality in developing countries, better estimates of the risk of long term sequelae such as wheezing after infection, better measures of protection in target populations, and data on the costs and benefits of vaccines for target populations are needed to support and justify funding this process. Addressing these challenges and needs should improve the efficiency and speed of achieving a safe and effective, licensed RSV vaccine. PMID:23598484

Rotavirus vaccination for Hong Kong children: an economic evaluation from the Hong Kong Government perspective.

PubMed

Ho, A M-H; Nelson, E A S; Walker, D G

2008-01-01

To perform an economic analysis of government-funded universal rotavirus vaccination in Hong Kong from the government's perspective. A Markov model of costs and effects (disability averted) associated with universal vaccination was compared with no vaccination. In both strategies, newborns were studied until 5 years of age or until they died, using cost, probability and utility data from the literature. The potential cost savings and cost effectiveness of vaccination were calculated and their sensitivities to changes in vaccine and health care costs, presumed decline in vaccine efficacy over time, and the use of discounting and age weights were determined. Depending on assumptions, the new rotavirus vaccines would be cost saving to the Hong Kong Government if they cost less than US$40-92 per course. Higher vaccine costs would quickly lead to an incremental cost-effectiveness ratio exceeding that of the gross national product per capita if the mortality rate of rotavirus gastroenteritis remained at zero. Based on 2002 demographic, cost and morbidity data and reasonable uncertainty estimates of these variables, a universal rotavirus vaccination programme paid for by the Hong Kong Government is cost neutral at a per course vaccine cost of US$40-92. For a fixed vaccine cost, the potential savings and cost effectiveness of the vaccine increase with higher estimated health care costs and vice versa.

Design of therapeutic vaccines as a novel antibody therapy for cardiovascular diseases.

PubMed

Nakagami, Hironori

2017-09-01

Vaccines are primarily used worldwide as a preventive medicine for infectious diseases and have recently been applied to cancer. We and others have developed therapeutic vaccines designed for cardiovascular diseases that are notably different from previous vaccines. In the case of cancer vaccines, a specific protein in cancer cells is a target antigen, and the activation of cytotoxic T cells (CTL) is required to kill and remove the antigen-presenting cancer cells. Our therapeutic vaccines work against hypertension by targeting angiotensin II (Ang II) as the antigen, which is an endogenous hormone. Therapeutic vaccines must avoid CTL activation and induce the blocking antibodies for Ang II. The goal of our therapeutic vaccine for cardiovascular diseases is to induce the specific antibody response toward the target protein without inducing T-cell or antibody-mediated inflammation through the careful selection of the target antigen, carrier protein and adjuvants. The goal of our therapeutic vaccine is similar to that of antibody therapy. Recently, multiple antibody-based drugs have been developed for cancer, immune-related diseases, and dyslipidemia, which are efficient but expensive. If the effect of a therapeutic vaccine is nearly equivalent to antibody therapy as an alternative approach, the lower medical cost and improvement in drug adherence can be advantages of therapeutic vaccines. In this review, we will describe our concept of therapeutic vaccines for cardiovascular diseases and the future directions of therapeutic vaccines as novel antibody therapies. Copyright © 2017. Published by Elsevier Ltd.

Cost effectiveness of prevaccination screening of health care workers for immunity to measles, rubella and mumps.

PubMed

Ferson, M J; Robertson, P W; Whybin, L R

1994-04-18

To determine the value of infection and vaccination histories as predictors of immunity to measles, rubella and mumps, and to compare the costs of various screening strategies with the cost of universal vaccination of health care workers. Staff employed by a Sydney children's hospital. Histories of measles, rubella and mumps infection or vaccination were compared with the results of serological testing to determine which historical statements had high positive predictive values (PPV) for immunity. Using this, we devised three prevaccination screening strategies and compared their costs with the cost of universal staff vaccination. Of 235 participants, 98.3% were serologically immune to measles, 96.6% to rubella and 83.0% to mumps. Historical statements indicating immunity with a PPV of more than 95% were histories of measles or of rubella vaccination, and personal recollection of mumps infection. Strategies using historical screening were cheaper than universal vaccination, which in turn was cheaper than using serological screening alone. Among health care workers at occupational risk of measles, rubella and mumps, the need for vaccination can be reduced by combining historical and serological screening. Where screening is felt to impose an administrative burden, a universal vaccination strategy costs 30%-50% more than strategies which use historical screening.

Antigenic variability: Obstacles on the road to vaccines against traditionally difficult targets.

PubMed

Servín-Blanco, R; Zamora-Alvarado, R; Gevorkian, G; Manoutcharian, K

2016-10-02

Despite the impressive impact of vaccines on public health, the success of vaccines targeting many important pathogens and cancers has to date been limited. The burden of infectious diseases today is mainly caused by antigenically variable pathogens (AVPs), which escape immune responses induced by prior infection or vaccination through changes in molecular structures recognized by antibodies or T cells. Extensive genetic and antigenic variability is the major obstacle for the development of new or improved vaccines against "difficult" targets. Alternative, qualitatively new approaches leading to the generation of disease- and patient-specific vaccine immunogens that incorporate complex permanently changing epitope landscapes of intended targets accompanied by appropriate immunomodulators are urgently needed. In this review, we highlight some of the most critical common issues related to the development of vaccines against many pathogens and cancers that escape protective immune responses owing to antigenic variation, and discuss recent efforts to overcome the obstacles by applying alternative approaches for the rational design of new types of immunogens.

Identification of Small Ligands Targeting Breast Cancer by In Vivo Screening of Peptide Libraries in Breast Cancer Patients

DTIC Science & Technology

2000-09-01

safety of IV injection of filamentous phage in humans, including the use of filamentous phage as an effective vaccine vehicle and also as a vehicle...Society National Surgical Adjuvant Breast and Bowel Project New England Cancer Society Society of Surgical Oncology Vermont Cancer Center...PROFESSIONAL SOCIETY COMMITTEES National Surgical Adjuvant Breast and Bowel Project 1991 -Present Principal Investigator for clinical trials, University of

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.

Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV.

PubMed

Wang, Xiaona; Wang, Li; Huang, Xuewei; Ma, Sunting; Yu, Meiling; Shi, Wen; Qiao, Xinyuan; Tang, Lijie; Xu, Yigang; Li, Yijing

2017-10-25

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences ( p < 0.05) in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.

Efficient priming of CD4 T cells by Langerin-expressing dendritic cells targeted with porcine epidemic diarrhea virus spike protein domains in pigs.

PubMed

Subramaniam, Sakthivel; Cao, Dianjun; Tian, Debin; Cao, Qian M; Overend, Christopher; Yugo, Danielle M; Matzinger, Shannon R; Rogers, Adam J; Heffron, C Lynn; Catanzaro, Nicholas; Kenney, Scott P; Opriessnig, Tanja; Huang, Yao-Wei; Labarque, Geoffrey; Wu, Stephen Q; Meng, Xiang-Jin

2017-01-02

Porcine epidemic diarrhea virus (PEDV) first emerged in the United States in 2013 causing high mortality and morbidity in neonatal piglets with immense economic losses to the swine industry. PEDV is an alpha-coronavirus replicating primarily in porcine intestinal cells. PEDV vaccines are available in Asia and Europe, and conditionally-licensed vaccines recently became available in the United States but the efficacies of these vaccines in eliminating PEDV from swine populations are questionable. In this study, the immunogenicity of a subunit vaccine based on the spike protein of PEDV, which was directly targeted to porcine dendritic cells (DCs) expressing Langerin, was assessed. The PEDV S antigen was delivered to the dendritic cells through a single-chain antibody specific to Langerin and the targeted cells were stimulated with cholera toxin adjuvant. This approach, known as "dendritic cell targeting," greatly improved PEDV S antigen-specific T cell interferon-γ responses in the CD4 pos CD8 pos T cell compartment in pigs as early as 7days upon transdermal administration. When the vaccine protein was targeted to Langerin pos DCs systemically through intramuscular vaccination, it induced higher serum IgG and IgA responses in pigs, though these responses require a booster dose, and the magnitude of T cell responses were lower as compared to transdermal vaccination. We conclude that PEDV spike protein domains targeting Langerin-expressing dendritic cells significantly increased CD4 T cell immune responses in pigs. The results indicate that the immunogenicity of protein subunit vaccines can be greatly enhanced by direct targeting of the vaccine antigens to desirable dendritic cell subsets in pigs. Copyright © 2016 Elsevier B.V. All rights reserved.

Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

PubMed Central

Yeaman, Michael R.; Filler, Scott G.; Schmidt, Clint S.; Ibrahim, Ashraf S.; Edwards, John E.; Hennessey, John P.

2014-01-01

Recent perspectives forecast a new paradigm for future “third generation” vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high-priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologs found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that (1) afford protective efficacy; (2) target an epitope from one organism that contributes to protective immunity against another; (3) cross-protect against multiple pathogens occupying a common anatomic or immunological niche; and/or (4) overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre-clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in pre-clinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3) where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target S. aureus. PMID:25309545

[Acceptability of vaccination against human papillomavirus (HPV) by pediatricians, mothers and young women in Ho Chi Minh City, Vietnam].

PubMed

Phan, D P T; Pham, Q T; Strobel, M; Tran, D S; Tran, T L; Buisson, Y

2012-12-01

Cervical cancer (CC) is almost always induced by some oncogenic types of human papillomavirus (HPV). In Vietnam, it is the first leading cause of cancer in women, with highest prevalence in Ho Chi Minh City (HCMC). Since 2006, prevention of the CC has been improved by licensure of recombinant vaccines directed against HPV 16 and 18, effective when administered before the age of first sexual intercourse. A national program for routine immunization of pre-adolescent girls in addition to cytological screening of adult women would greatly reduce the impact of CC in Vietnam but vaccines remain expensive and it is unclear how this strategy would be accepted by the target population. The aim of this study was to assess the acceptability of HPV vaccination by pediatricians, mothers with a daughter aged 9-15 years and young women aged 16-26 years in HCMC. Between March and June 2010, a cross-sectional survey of knowledge and attitudes was administered to 115 pediatricians in the pediatric hospital, 210 mothers and 400 young women attending the gynecology department of the University Hospital. Pediatricians generally had a good perception of the risk but they still lacked knowledge about HPV vaccination, given by 66% of them. Among mothers, 18% knew the relationship between HPV infection and CC, 43% had heard of HPV vaccination and 40% agreed to vaccinate their daughter. Among young women, 35% knew the risk, 49% knew the vaccine and 38% wanted to be vaccinated. Level of education, amount of income and celibacy were positively related to intention to be vaccinated. The lack of information on HPV vaccination and the high cost of vaccines were the main causes of refusal or indecision. Routine HPV vaccination of girls in HCMC will be well accepted by the population if a large campaign of health education is implemented by the government and if the affordability of vaccines is facilitated. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Measles resurgence following a nationwide measles vaccination campaign in Nigeria, 2005-2008.

PubMed

Weldegebriel, Goitom G; Gasasira, Alex; Harvey, Pauline; Masresha, Balcha; Goodson, James L; Pate, Muhammad A; Abanida, Emmanuel; Chevez, Ana

2011-07-01

From 1990 through 2008, routine immunization coverage of measles vaccine in Nigeria ranged from 35% to 70%. Nigeria conducted a nationwide measles vaccination campaign in 2 phases during 2005-2006 that targeted children aged 9 months to 14 years; in 2008, a nationwide follow-up campaign that targeted children aged 9 months to 4 years was conducted in 2 phases. Despite these efforts, measles cases continued to occur. This is a descriptive study that reviewed the measles immunization coverage data from administrative, World Health Organization, United Nations Children's Fund, survey, and supplemental immunization activities data. Measles surveillance data were analyzed from case-based surveillance reports. Confirmed measles cases increased from 383 in 2006 to 2542 in 2007 and to 9510 in 2008. Of the confirmed cases in 2008, 717 (30%) occurred in children <2 years of age, 1145 (48%) in children 2-4 years of age, and 354 (14%) were in children 5-14 years of age. In 2008, the measles case fatality rate was 1.2%. Suboptimal routine coverage and the wide interval between the catch-up and follow-up campaigns likely led to an accumulation of children susceptible to measles. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Poxvirus-vectored vaccines for rabies--a review.

PubMed

Weyer, Jacqueline; Rupprecht, Charles E; Nel, Louis H

2009-11-27

Oral rabies vaccination of target reservoir species has proved to be one of the pillars of successful rabies elimination programs. The use of live attenuated rabies virus vaccines has been extensive but several limitations hamper its future use. A recombinant vaccinia-rabies vaccine has also been successfully used for the oral vaccination of several species. Nevertheless, its lack of efficacy in certain important rabies reservoirs and concerns on the use of this potent live virus as vaccine carrier (vector) impair the expansion of its use for new target species and new areas. Several attenuated and host-restricted poxvirus alternatives, which supposedly offer enhanced safety, have been investigated. Once again, efficacy in certain target species and innocuity through the oral route remain major limitations of these vaccines. Alternative recombinant vaccines using adenovirus as an antigen delivery vector have been extensively investigated and may provide an important addition to the currently available oral rabies vaccine repertoire, but are not the primary subject of this review.

Prevalence and factors associated with 2009 to 2011 influenza vaccinations at a university medical center.

PubMed

Crowley, Kathleen A; Myers, Ronnie; Magda, Lori A; Morse, Stephen S; Brandt-Rauf, Paul; Gershon, Robyn R M

2013-09-01

Information on the rates and factors associated with influenza vaccinations, although limited, is important because it can inform the development of effective vaccination campaigns in a university medical center setting. A study was conducted in 2011 to identify individual and organizational level barriers and facilitators to influenza vaccination among clinical and nonclinical personnel (N = 428) from a major university medical center. Seventy-one percent of clinical personnel (n = 170) reported pandemic H1N1 vaccination compared with 27% of nonclinical personnel (n = 258), even though vaccine was made widely available to all personnel at no cost. Similarly, disparate rates between clinical and nonclinical personnel were noted for the 2009/2010 seasonal influenza vaccine (82% vs 42%, respectively) and 2010/2011 combination (pandemic plus seasonal) influenza vaccine (73% vs 28%, respectively). Factors associated with pandemic vaccination in nonclinical personnel included the following: high level of influenza-related knowledge, concern regarding influenza contagion, history of previous influenza vaccinations or influenza illness, participation in vaccine-related training, and awareness of the institution's written pandemic plan. For clinicians, past history of seasonal influenza vaccination was associated with pandemic vaccination. For all participants, taking any 1 or more of the 3 influenza vaccines available in 2009 to 2011 was associated with intent to take a hypothetical future novel pandemic vaccine (odds ratio, 6.7; 95% confidence interval: 4.32-10.44; P < .001). Most of the risk factors associated with lack of vaccination uptake are amenable to organizational strategies. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Higher Tetanus Toxoid Immunity 2 Years After PsA-TT Introduction in Mali.

PubMed

Basta, Nicole E; Borrow, Ray; Berthe, Abdoulaye; Onwuchekwa, Uma; Dembélé, Awa Traoré Eps; Almond, Rachael; Frankland, Sarah; Patel, Sima; Wood, Daniel; Nascimento, Maria; Manigart, Olivier; Trotter, Caroline L; Greenwood, Brian; Sow, Samba O

2015-11-15

In 2010, mass vaccination with a then-new meningococcal A polysaccharide-tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction. Using a household-based, age-stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels ≥0.1 IU/mL (indicating short-term protection) and ≥1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models. Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre-PsA-TT, significantly higher GMCs in all age-sex strata were observed 2 years after PsA-TT introduction. The percentage with short-term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6-36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7-43.3; P < .0001) pre- and postvaccination. Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

A universal polysaccharide conjugated vaccine against O111 E. coli

PubMed Central

Andrade, Gabrielle R; New, Roger R C; Sant’Anna, Osvaldo A; Williams, Neil A; Alves, Rosely C B; Pimenta, Daniel C; Vigerelli, Hugo; Melo, Bruna S; Rocha, Letícia B; Piazza, Roxane M F; Mendonça-Previato, Lucia; Domingos, Marta O

2014-01-01

E. coli O111 strains are responsible for outbreaks of blood diarrhea and hemolytic uremic syndrome throughout the world. Because of their phenotypic variability, the development of a vaccine against these strains which targets an antigen that is common to all of them is quite a challenge. Previous results have indicated, however, that O111 LPS is such a candidate, but its toxicity makes LPS forbidden for human use. To overcome this problem, O111 polysaccharides were conjugated either to cytochrome C or to EtxB (a recombinant B subunit of LT) as carrier proteins. The O111-cytochrome C conjugate was incorporated in silica SBA-15 nanoparticles and administered subcutaneously in rabbits, while the O111-EtxB conjugate was incorporated in VaxcineTM, an oil-based delivery system, and administered orally in mice. The results showed that one year post-vaccination, the conjugate incorporated in silica SBA-15 generated antibodies in rabbits able to inhibit the adhesion of all categories of O111 E. coli to epithelial cells. Importantly, mice immunized orally with the O111-EtxB conjugate in VaxcineTM generated systemic and mucosal humoral responses against all categories of O111 E. coli as well as antibodies able to inhibit the toxic effect of LT in vitro. In summary, the results obtained by using 2 different approaches indicate that a vaccine that targets the O111 antigen has the potential to prevent diarrhea induced by O111 E. coli strains regardless their mechanism of virulence. They also suggest that a conjugated vaccine that uses EtxB as a carrier protein has potential to combat diarrhea induced by ETEC. PMID:25483465

Human Papillomavirus Vaccine Stages of Change among Male and Female University Students: Ready or Not?

ERIC Educational Resources Information Center

Patel, Divya A.; Grunzweig, Katherine A.; Zochowski, Melissa K.; Dempsey, Amanda F.; Carlos, Ruth C.; Dalton, Vanessa K.

2013-01-01

Objective: To examine gender differences in human papillomavirus (HPV) vaccine stages of change following the recommendations for permissive use of HPV vaccine in males. Participants: Students aged 18-26 attending a large, public, Midwest university in April 2010. Methods: Participants completed a self-administered, online questionnaire. HPV…

Human papillomavirus and vaccine-related perceptions among men who have sex with men: a systematic review.

PubMed

Nadarzynski, Tom; Smith, Helen; Richardson, Daniel; Jones, Christina J; Llewellyn, Carrie D

2014-11-01

Targeted human papillomavirus (HPV) vaccine could prevent HPV-related cancers and genital warts among men who have sex with men (MSM). In order to develop effective vaccination programmes for MSM, it is crucial to understand their knowledge, beliefs about HPV and attitudes towards HPV vaccine. A systematic search of 10 databases examined articles investigating HPV knowledge and HPV-related perceptions among MSM. Each paper was assessed to identify potential research directions in the context of targeted HPV vaccination for MSM. We identified 16 studies that included 5185 MSM and conducted mainly in North America. Generally, participants were over 26 years old, had poor-to-moderate knowledge about HPV and were not concerned about HPV-related diseases. Over a half of MSM were willing to accept HPV vaccine, if offered. However, there was large variability in HPV vaccine acceptability, partially due to inconsistencies in methods of ascertainment but also different levels of HPV vaccine awareness. Despite several misconceptions and poor knowledge of HPV infection, MSM might be receptive to HPV vaccination. However, further research is needed to identify which factors contribute to potential vaccine uptake in hypothetical MSM-targeted HPV vaccination. Future studies need to target those MSM with little sexual experience, who would benefit most from HPV vaccination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Stakeholder attitudes toward influenza vaccination policy in the United States.

PubMed

Berman, Pamela Protzel; Orenstein, Walter A; Hinman, Alan R; Gazmararian, Julie

2010-11-01

There is growing interest in simplifying recommendations to vaccinate Americans against influenza. The article discusses interviews with 35 stakeholders from the medical, public health, educational, insurance, and vaccine industry sectors to assess the potential for policy change, and discusses questions posed to the interviewees on current and future influenza vaccination policy and barriers to policy change. About 97% of respondents support the expansion of vaccination for all school-age children, and about 95% support universal vaccination, but there are reservations expressed by the respondents, despite the support for this policy change. Barriers to influenza vaccination recommendations include access, supply, confusing recommendations, and public perceptions. Barriers to universal vaccination include lack of infrastructure, cost, need for education, and vaccine supply. Issues concerning resources and education are challenges that impede policy change. The study findings can be useful to policy makers and practitioners for reviewing U.S. vaccination policy and changes to the policy.

Barriers and facilitators to uptake of the school-based HPV vaccination programme in an ethnically diverse group of young women.

PubMed

Batista Ferrer, Harriet; Trotter, Caroline L; Hickman, Matthew; Audrey, Suzanne

2016-09-01

To identify the barriers and facilitators to uptake of the HPV vaccine in an ethnically diverse group of young women in the south west of England. Three school-based vaccination sessions were observed. Twenty-three young women aged 12 to 13 years, and six key informants, were interviewed between October 2012 and July 2013. Data were analysed using thematic analysis and the Framework method for data management. The priority given to preventing cervical cancer in this age group influenced whether young women received the HPV vaccine. Access could be affected by differing levels of commitment by school staff, school nurses, parents and young women to ensure parental consent forms were returned. Beliefs and values, particularly relevant to minority ethnic groups, in relation to adolescent sexual activity may affect uptake. Literacy and language difficulties undermine informed consent and may prevent vaccination. The school-based HPV vaccination programme successfully reaches the majority of young women. However, responsibility for key aspects remain unresolved which can affect delivery and prevent uptake for some groups. A multi-faceted approach, targeting appropriate levels of the socio-ecological model, is required to address procedures for consent and cultural and literacy barriers faced by minority ethnic groups, increase uptake and reduce inequalities. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health.

Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

PubMed

Khurana, Surender; Loving, Crystal L; Manischewitz, Jody; King, Lisa R; Gauger, Phillip C; Henningson, Jamie; Vincent, Amy L; Golding, Hana

2013-08-28

Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.

An estimate of the public health impact and cost-effectiveness of universal vaccination with a 9-valent HPV vaccine in Germany.

PubMed

Largeron, Nathalie; Petry, Karl Ulrich; Jacob, Jorge; Bianic, Florence; Anger, Delphine; Uhart, Mathieu

2017-02-01

Since 2007, the German Standing Vaccination Committee recommends HPV vaccination for girls aged 12-17 with a 2- (Cervarix®) or 4-valent (Gardasil®) vaccine. A 9-valent vaccine (Gardasil 9®) recently received a European market authorization in 2015. A dynamic transmission model was calibrated to the German setting and used to estimate costs and QALYs associated with vaccination strategies. Compared to the current vaccination program, the 9-valent vaccine extended to boys shows further reductions of 24% in the incidence of cervical cancer, 30% and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new strategy is associated with an ICER of 22,987€ per QALY gained, decreasing to 329€ when considering the vaccine switch for girls-only. Universal vaccination with the 9-valent vaccine can yield significant health benefits when compared to the current program.

A DNA Vaccine That Targets Hemagglutinin to Antigen-Presenting Cells Protects Mice against H7 Influenza

PubMed Central

Andersen, Tor Kristian; Zhou, Fan; Cox, Rebecca; Bogen, Bjarne

2017-01-01

ABSTRACT Zoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently, no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to either major histocompatibility complex class II molecules or chemokine receptors 1, 3, and 5 (CCR1/3/5) that are expressed on antigen-presenting cells (APC). A single DNA vaccination with APC-targeted HA significantly increased antibody levels in sera compared to nontargeted control vaccines. The antibodies were confirmed neutralizing in an H7 pseudotype-based neutralization assay. Furthermore, the APC-targeted vaccines increased the levels of antigen-specific cytotoxic T cells, and a single DNA vaccination could confer protection against a lethal challenge with influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have developed a vaccine that rapidly could contribute protection against a pandemic threat from avian influenza. IMPORTANCE Highly pathogenic avian influenza H7 constitute a pandemic threat that can cause severe illness and death in infected individuals. Vaccination is the main method of prophylaxis against influenza, but current vaccine strategies fall short in a pandemic situation due to a prolonged production time and insufficient production capabilities. In contrast, a DNA vaccine can be rapidly produced and deployed to prevent the potential escalation of a highly pathogenic influenza pandemic. We here demonstrate that a single DNA delivery of hemagglutinin from an H7 influenza could mediate full protection against a lethal challenge with H7N1 influenza in mice. Vaccine efficacy was contingent on targeting of the secreted vaccine protein to antigen-presenting cells. PMID:28931687

Rotavirus vaccine RIX4414 (Rotarix™): a pharmacoeconomic review of its use in the prevention of rotavirus gastroenteritis in developing countries.

PubMed

Plosker, Greg L

2011-11-01

This article provides an overview of the clinical profile of rotavirus vaccine RIX4414 (Rotarix™) in the prevention of rotavirus gastroenteritis (RVGE) in developing countries, followed by a comprehensive review of pharmacoeconomic analyses with the vaccine in low- and middle-income countries. RVGE is associated with significant morbidity and mortality among children <5 years of age in developing countries. The protective efficacy of a two-dose oral series of rotavirus vaccine RIX4414 has been demonstrated in several well designed clinical trials conducted in developing countries, and the 'real-world' effectiveness of the vaccine has also been shown in naturalistic and case-control trials after the introduction of universal vaccination programmes with RIX4414 in Latin American countries. The WHO recommends universal rotavirus vaccination programmes for all countries. Numerous modelled cost-effectiveness analyses have been conducted with rotavirus vaccine RIX4414 across a wide range of low- and middle-income countries. Although data sources and assumptions varied across studies, results of the analyses consistently showed that the introduction of the vaccine as part of a national vaccination programme would be very (or highly) cost effective compared with no rotavirus vaccination programme, according to widely used cost-effectiveness thresholds for developing countries. Vaccine price was not known at the time the analyses were conducted and had to be estimated. In sensitivity analyses, rotavirus vaccine RIX4414 generally remained cost effective at the highest of a range of possible vaccine prices considered. Despite these favourable results, decisions regarding the implementation of universal vaccination programmes with RIX4414 may also be contingent on budgetary and other factors, underscoring the importance of subsidized vaccination programmes for poor countries through the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization).

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

Kunkel Lecture: Fundamental immunodeficiency and its correction

PubMed Central

2017-01-01

“Fundamental immunodeficiency” is the inability of the encoded immune system to protect an otherwise healthy host from every infection that could threaten its life. In contrast to primary immunodeficiencies, fundamental immunodeficiency is not rare but nearly universal. It results not from variation in a given host gene but from the rate and extent of variation in the genes of other organisms. The remedy for fundamental immunodeficiency is “adopted immunity,” not to be confused with adaptive or adoptive immunity. Adopted immunity arises from four critical societal contributions to the survival of the human species: sanitation, nutrition, vaccines, and antimicrobial agents. Immunologists have a great deal to contribute to the development of vaccines and antimicrobial agents, but they have focused chiefly on vaccines, and vaccinology is thriving. In contrast, the effect of antimicrobial agents in adopted immunity, although fundamental, is fragile and failing. Immunologists can aid the development of sorely needed antimicrobial agents, and the study of antimicrobial agents can help immunologists discover targets and mechanisms of host immunity. PMID:28701368

Vaccine Targeting of Subdominant CD8+ T Cell Epitopes Increases the Breadth of the T Cell Response upon Viral Challenge, but May Impair Immediate Virus Control.

PubMed

Steffensen, Maria A; Pedersen, Louise H; Jahn, Marie L; Nielsen, Karen N; Christensen, Jan P; Thomsen, Allan R

2016-03-15

As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future vaccines should preferentially target subdominant epitopes, the idea being that this should allow a greater breadth of the induced T cell response and, hence, a greater efficiency in controlling escape variants. However, to our knowledge the evidence supporting this concept is limited at best. To improve upon this, we used the murine lymphocytic choriomeningitis virus model and adenoviral vectors to compare a vaccine expressing unmodified Ag to a vaccine expressing the same Ag without its immunodominant epitope. We found that removal of the dominant epitope allowed the induction of CD8(+) T cell responses targeting at least two otherwise subdominant epitopes. Importantly, the overall magnitude of the induced T cell responses was similar, allowing us to directly compare the efficiency of these vaccines. Doing this, we observed that mice vaccinated with the vaccine expressing unmodified Ag more efficiently controlled an acute viral challenge. In the course of a more chronic viral infection, mice vaccinated using the vaccine targeting subdominant epitopes caught up with the conventionally vaccinated mice, and analysis of the breadth of the CD8(+) T cell response revealed that this was notably greater in the former mice. However, under the conditions of our studies, we never saw any functional advantage of this. This may represent a limitation of our model, but clearly our findings underscore the importance of carefully weighing the pros and cons of changes in epitope targeting before any implementation. Copyright © 2016 by The American Association of Immunologists, Inc.

Human papillomavirus vaccination coverage in Luxembourg - Implications of lowering and restricting target age groups.

PubMed

Latsuzbaia, Ardashel; Arbyn, Marc; Weyers, Steven; Mossong, Joël

2018-04-25

In Luxembourg, a national Human Papillomavirus (HPV) vaccination programme was introduced in 2008, targeting 12-17 year old girls offering a choice of bivalent or quadrivalent vaccine free of charge. In 2015, the programme was changed offering the bivalent vaccine only to 11-13 year old girls. The aim of this study was to evaluate the HPV vaccination coverage, to assess the impact of age target changes and compare vaccination coverage to other European countries. Anonymous HPV vaccination records consisting of individual vaccine doses obtained free of charge in pharmacies between 2008 and 2016 were extracted from the Luxembourgish Social Security database. Additional aggregate tables by nationality and municipality were analysed. Of the target cohort of 39,610 girls born between 1991 and 2003 residing in Luxembourg, 24,550 (62.0%) subjects obtained at least one dose, 22,082 (55.7%) obtained at least two doses, and 17,197 (43.4%) obtained three doses of HPV vaccine. The mean age at first dose was 13.7 years during 2008-14 and 12.7 years in 2016 after the age target change. Coverage varied significantly by nationality (p < 0.0001): Portuguese (80%), former Yugoslavs (74%), Luxembourgish (54%), Belgian (52%), German (47%), French (39%) and other nationalities (51%). Coverage varied also by geographical region, with lower rates (<50%) noted in some Northern and Central areas of Luxembourg (range: 38% to 78%). Overall HPV vaccination coverage in Luxembourg is moderate and varied by nationality and region. The policy changes in 2015 did not have a substantial impact except lowering age at initiating vaccination. Options to improve coverage deserve further investigation. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Rotavirus vaccines in Israel: Uptake and impact.

PubMed

Muhsen, Khitam; Cohen, Daniel

2017-07-03

We present an overview of the impact of universal rotavirus immunization with the pentavalent vaccine, RotaTeq, which was introduced in Israel in 2010. The vaccine is given free of charge at age 2, 4 and 6 months, with an 80% coverage that was shortly achieved during the universal immunization period. Compared to pre-universal immunization years (2008-2010), a reduction of 66-68% in the incidence of rotavirus gastroenteritis (RVGE) hospitalizations was observed in 2011-2015 among children aged 0-23 months in central and northern Israel. In southern Israel a reduction of 80-88% in RVGE hospital visit rate was found among Jewish children aged 0-23 months in 2011-2013. Among Bedouins, the respective decline was 62-75%. A significant reduction of 59% was also observed in RVGE clinic visits, presumably representing less severe illness. Indirect benefit was evident in children aged 24-59 months who were ineligible for universal immunization. Vaccine effectiveness against RVGE hospitalization was estimated at 86% in children aged 6-23 months. Changes in the circulating rotavirus genotypes occurred but the contribution of vaccine induced immune pressure is unclear. Universal rotavirus immunization was followed by an impressive decrease in the burden of RVGE in young children in Israel, likely attributed to good vaccine coverage and effectiveness.

Traditional and New Influenza Vaccines

PubMed Central

Wong, Sook-San

2013-01-01

SUMMARY The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a “universal” influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets. PMID:23824369

Intervene before leaving: clustered lot quality assurance sampling to monitor vaccination coverage at health district level before the end of a yellow fever and measles vaccination campaign in Sierra Leone in 2009.

PubMed

Pezzoli, Lorenzo; Conteh, Ishata; Kamara, Wogba; Gacic-Dobo, Marta; Ronveaux, Olivier; Perea, William A; Lewis, Rosamund F

2012-06-07

In November 2009, Sierra Leone conducted a preventive yellow fever (YF) vaccination campaign targeting individuals aged nine months and older in six health districts. The campaign was integrated with a measles follow-up campaign throughout the country targeting children aged 9-59 months. For both campaigns, the operational objective was to reach 95% of the target population. During the campaign, we used clustered lot quality assurance sampling (C-LQAS) to identify areas of low coverage to recommend timely mop-up actions. We divided the country in 20 non-overlapping lots. Twelve lots were targeted by both vaccinations, while eight only by measles. In each lot, five clusters of ten eligible individuals were selected for each vaccine. The upper threshold (UT) was set at 90% and the lower threshold (LT) at 75%. A lot was rejected for low vaccination coverage if more than 7 unvaccinated individuals (not presenting vaccination card) were found. After the campaign, we plotted the C-LQAS results against the post-campaign coverage estimations to assess if early interventions were successful enough to increase coverage in the lots that were at the level of rejection before the end of the campaign. During the last two days of campaign, based on card-confirmed vaccination status, five lots out of 20 (25.0%) failed for having low measles vaccination coverage and three lots out of 12 (25.0%) for low YF coverage. In one district, estimated post-campaign vaccination coverage for both vaccines was still not significantly above the minimum acceptable level (LT = 75%) even after vaccination mop-up activities. C-LQAS during the vaccination campaign was informative to identify areas requiring mop-up activities to reach the coverage target prior to leaving the region. The only district where mop-up activities seemed to be unsuccessful might have had logistical difficulties that should be further investigated and resolved.

Human papillomavirus vaccine recommendations and agreement with mandated human papillomavirus vaccination for 11-to-12-year-old girls: a statewide survey of Texas physicians.

PubMed

Kahn, Jessica A; Cooper, H Paul; Vadaparampil, Susan T; Pence, Barbara C; Weinberg, Armin D; LoCoco, Salvatore J; Rosenthal, Susan L

2009-08-01

The purpose of this study was to examine Texas physicians' recommendations for the quadrivalent human papillomavirus (HPV) vaccine in 11-to-12-year-old girls, intention to recommend HPV vaccines to 11-to-12-year-old boys, and attitudes about mandated HPV vaccination for 11-to-12-year-old girls. We conducted a cross-sectional, web-based survey of Texas physicians who provide direct patient care in family medicine, pediatrics, obstetrics/gynecology, and internal medicine in September 2008. The three outcome variables were: HPV vaccine recommendations to 11-to-12-year-old girls, likelihood of recommending the vaccine to 11-to-12-year-old boys, and agreement with mandated vaccination of 11-to-12-year-old girls. Univariate and logistic regression analyses were used to determine practice-related and attitudinal factors associated with each outcome. Of the 1,122 respondents, 48.5% stated they always recommended HPV vaccines to girls, 68.4% were likely to recommend the vaccine to boys, and 41.7% agreed with mandated vaccination. In multivariate logistic regression models, variables independently associated with recommendation to 11-to-12-year-old girls included: percentage of patients with Medicaid [odds ratio (OR), 1.02; 95% confidence interval (95% CI), 1.01-1.03], academic versus nonacademic practice (OR, 2.11; 95% CI, 1.05-4.23), office procedures to maximize vaccination (OR, 1.25; 95% CI, 1.01-1.56), HPV knowledge (OR, 1.25; 95% CI, 1.04-1.49), valuing HPV vaccine information from both professional organizations (OR, 1.90; 95% CI, 1.15-3.16) and professional conferences (OR, 1.68; 95% CI, 1.10-2.57), belief in mandated HPV vaccination (OR, 5.38; 95% CI, 3.28-8.83), and barriers to vaccination (OR, 1.08; 95% CI, 1.00-1.16). Half of the physicians in this study did not follow current recommendations for universal HPV vaccination of 11-to-12-year-old girls. Factors linked to vaccine recommendations may be targeted in educational or policy interventions.

Targeted human papillomavirus vaccination of men who have sex with men in the USA: a cost-effectiveness modelling analysis.

PubMed

Kim, Jane J

2010-12-01

A vaccine targeting human papillomavirus (HPV) types 16 and 18, which are associated with 80% of anal cancers, is efficacious in men. High-risk populations such as men who have sex with men (MSM) might especially benefit from vaccination. I aimed to estimate the cost-effectiveness of HPV vaccination of MSM in the USA. I constructed decision-analytic models to estimate the direct health and economic outcomes of HPV vaccination (against types 6, 11, 16, and 18) for prevention of HPV-related anal cancer and genital warts. The model parameters that were varied were age at vaccination (12 years, 20 years, and 26 years), previous exposure to vaccine-targeted HPV types, and prevalence of HIV-1. I used the models to conduct sensitivity analyses, including duration of vaccine protection, vaccine cost, and burden of anal cancer and genital warts. In a scenario of HPV vaccination of MSM at 12 years of age without previous exposure to HPV, compared with no vaccination, vaccination cost US$15,290 per quality-adjusted life-year gained. In scenarios where MSM are vaccinated at 20 years or 26 years of age, after exposure to HPV infections, the cost-effectiveness ratios worsened, but were less than $50,000 per quality-adjusted life-year under most scenarios. For example, HPV vaccination of MSM at 26 years cost $37,830 per quality-adjusted life-year when previous exposure to all vaccine-targeted HPV types was assumed to be 50%. Outcomes were most sensitive to variations in anal cancer incidence, duration of vaccine protection, and HIV prevalence in MSM. HPV vaccination of MSM is likely to be a cost-effective intervention for the prevention of genital warts and anal cancer. US National Cancer Institute. Copyright © 2010 Elsevier Ltd. All rights reserved.

New generation of oral mucosal vaccines targeting dendritic cells

PubMed Central

Owen, Jennifer L.; Sahay, Bikash; Mohamadzadeh, Mansour

2013-01-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including B. anthracis in experimental models of disease. PMID:23835515

Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

PubMed Central

Barh, Debmalya; Barve, Neha; Gupta, Krishnakant; Chandra, Sudha; Jain, Neha; Tiwari, Sandeep; Leon-Sicairos, Nidia; Canizalez-Roman, Adrian; Rodrigues dos Santos, Anderson; Hassan, Syed Shah; Almeida, Síntia; Thiago Jucá Ramos, Rommel; Augusto Carvalho de Abreu, Vinicius; Ribeiro Carneiro, Adriana; de Castro Soares, Siomar; Luiz de Paula Castro, Thiago; Miyoshi, Anderson; Silva, Artur; Kumar, Anil; Narayan Misra, Amarendra; Blum, Kenneth; Braverman, Eric R.; Azevedo, Vasco

2013-01-01

Vibrio cholerae is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, Vibrio infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (ompU, uppP and yajC) for most of the pathogenic Vibrio strains. Two targets (uppP and yajC) are novel to Vibrio, and two targets (uppP and ompU) can be used to develop both drugs and vaccines (dual targets) against broad spectrum Vibrio serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from Piper betel. Seven compounds were identified first time from Piper betel to be highly effective to render the function of these targets to identify them as emerging potential drugs against Vibrio. Our preliminary validation suggests that these identified peptide vaccines and betel compounds are highly effective against Vibrio cholerae. Currently we are exhaustively validating these targets, candidate peptide vaccines, and betel derived lead compounds against a number of Vibrio species. PMID:23382822

Estimating the cost-effectiveness profile of a universal vaccination programme with a nine-valent HPV vaccine in Austria.

PubMed

Boiron, L; Joura, E; Largeron, N; Prager, B; Uhart, M

2016-04-16

HPV is a major cancer-causing factor in both sexes in the cervix, vulva, vagina, anus, penis, oropharynx as well as the causal factor in other diseases such as genital warts and recurrent respiratory papillomatis. In the context of the arrival of a nonavalent HPV vaccine (6/11/16/18/31/33/45/52/58), this analysis aims to estimate the public health impact and the incremental cost-effectiveness of a universal (girls and boys) vaccination program with a nonavalent HPV vaccine as compared to the current universal vaccination program with a quadrivalent HPV vaccine (6/11/16/18), in Austria. A dynamic transmission model including a wide range of health and cost outcomes related to cervical, anal, vulvar, vaginal diseases and genital warts was calibrated to Austrian epidemiological data. The clinical impact due to the 5 new types was included for cervical and anal diseases outcomes only. In the base case, a two-dose schedule, lifelong vaccine type-specific protection and a vaccination coverage rate of 60% and 40% for girls and boys respectively for the 9-year old cohorts were assumed. A cost-effectiveness threshold of €30,000/QALY-gained was considered. Universal vaccination with the nonavalent vaccine was shown to reduce the incidence of HPV16/18/31/33/45/52/58 -related cervical cancer by 92%, the related CIN2/3 cases by 96% and anal cancer by 83% and 76% respectively in females and males after 100 years, relative to 75%, 76%, 80% and 74% with the quadrivalent vaccine, respectively. Furthermore, the nonavalent vaccine was projected to prevent an additional 14,893 cases of CIN2/3 and 2544 cases of cervical cancer, over 100 years. Depending on the vaccine price, the strategy was shown to be from cost-saving to cost-effective. The present evaluation showed that vaccinating 60% of girls and 40% of boys aged 9 in Austria with a 9-valent vaccine will substantially reduce the incidence of cervical cancer, CIN and anal cancer compared to the existing strategy. The vaccination strategies performed with the 9-valent vaccine in the current study were all found to be cost-effective compared to the current quadrivalent vaccination strategy by considering a cost-effectiveness threshold of 30,000€/QALY gained.

Effectiveness of rotavirus pentavalent vaccine under a universal immunization programme in Israel, 2011-2015: a case-control study.

PubMed

Muhsen, K; Anis, E; Rubinstein, U; Kassem, E; Goren, S; Shulman, L M; Ephros, M; Cohen, D

2018-01-01

The use of rotavirus pentavalent vaccine (RotaTeq ® ) as a sole vaccine within rotavirus universal immunization programmes remains limited. We examined the effectiveness of RotaTeq in preventing rotavirus gastroenteritis (RVGE) hospitalization in Israel, after the introduction of universal immunization against the disease. A test-negative case-control study included age-eligible children for universal RotaTeq immunization (aged 2-59 months, born in 2011-2015). Cases (n = 98) were patients who tested positive for rotavirus by immunochromatography; those who tested negative (n = 628) comprised the control group. Information on rotavirus immunization history was obtained through linkage with a national immunization registry. Vaccination status was compared between cases and controls, adjusted odds ratios (aORs) were obtained from logistic regression models, and vaccine effectiveness calculated as (1 - aOR)*100. Immunization with RotaTeq was less frequent in RVGE cases (73.5%) than in controls (90.1%), p < 0.001; this association persisted after controlling for potential confounders. Effectiveness of the complete vaccine series was estimated at 77% (95% confidence interval (CI): 49-90) in children aged 6-59 months, and 86% (95% CI: 65-94) in children aged 6-23 months; whereas for the incomplete series, the respective estimates were 72% (95% CI: 28-89) and 75% (95% CI: 30-91). Vaccine effectiveness was estimated at 79% (95% CI: 45-92) against G1P[8]-associated RVGE hospitalizations and 69% (95% CI: 11-89) against other genotype-RVGE hospitalizations. High effectiveness of RotaTeq as the sole rotavirus vaccine in a universal immunization programme was demonstrated in a high-income country. Although partial vaccination conferred protection, completing the vaccine series is warranted to maximize the benefit. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Low uptake of influenza vaccine among university students: evaluating predictors beyond cost and safety concerns.

PubMed

Bednarczyk, Robert A; Chu, Samantha L; Sickler, Heather; Shaw, Jana; Nadeau, Jessica A; McNutt, Louise-Anne

2015-03-30

Annual influenza vaccine coverage for young adults (including college students) remains low, despite a 2011 US recommendation for annual immunization of all people 6 months and older. College students are at high risk for influenza morbidity given close living and social spaces and extended travel during semester breaks when influenza circulation typically increases. We evaluated influenza vaccine uptake following an on-campus vaccine campaign at a large, public New York State university. Consecutive students visiting the University Health Center were recruited for a self-administered, anonymous, written survey. Students were asked about recent influenza vaccination, barriers to influenza vaccination, and willingness to get vaccinated to protect other vulnerable individuals they may encounter. Frequencies and proportions were evaluated. Of 653 students approached, 600 completed surveys (92% response proportion); respondents were primarily female (61%) and non-Hispanic white (59%). Influenza vaccine coverage was low (28%). Compared to coverage among non-Hispanic white students (30%), coverage was similar among Hispanic (30%) and other race/ethnicity students (28%) and lowest among non-Hispanic black students (17%). Among the unvaccinated, the most commonly selected vaccination barriers were "Too lazy to get the vaccine" (32%) and "Don't need the vaccine because I'm healthy" (29%); 6% of unvaccinated students cited cost as a barrier. After being informed that influenza vaccination of young, healthy people can protect other vulnerable individuals (e.g., infants, elderly), 71% of unvaccinated students indicated this would increase their willingness to get vaccinated. Influenza vaccine uptake among college students is very low. While making vaccine easily obtained may increase vaccine uptake, college students need to be motivated to get vaccinated. Typically healthy students may not perceive a need for influenza vaccine. Education about vaccinating healthy individuals to prevent the spread of influenza to close contacts, such as vulnerable family members, may provide this motivation to get vaccinated. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Factors effecting influenza vaccination uptake among health care workers: a multi-center cross-sectional study.

PubMed

Asma, Süheyl; Akan, Hülya; Uysal, Yücel; Poçan, A Gürhan; Sucaklı, Mustafa Haki; Yengil, Erhan; Gereklioğlu, Çiğdem; Korur, Aslı; Başhan, İbrahim; Erdogan, A Ferit; Özşahin, A Kürşat; Kut, Altuğ

2016-05-04

The present study aimed to identify factors affecting vaccination against influenza among health professionals. We used a multi-centre cross-sectional design to conduct an online self-administered questionnaire with physicians and nurses at state and foundation university hospitals in the south-east of Turkey, between 1 January 2015 and 1 February 2015. The five participating hospitals provided staff email address lists filtered for physicians and nurses. The questionnaire comprised multiple choice questions covering demographic data, knowledge sources, and Likert-type items on factors affecting vaccination against influenza. The target response rate was 20 %. In total, 642 (22 %) of 2870 health professionals (1220 physicians and 1650 nurses) responded to the questionnaire. Participants' mean age was 29.6 ± 9.2 years (range 17-62 years); 177 (28.2 %) were physicians and 448 (71.3 %) were nurses. The rate of regular vaccination was 9.2 % (15.2 % for physicians and 8.2 % for nurses). Increasing age, longer work duration in health services, being male, being a physician, working in an internal medicine department, having a chronic disease, and living with a person over 65 years old significantly increased vaccination compliance (p < 0.05). We found differences between vaccine compliant and non-compliant groups for expected benefit from vaccination, social influences, and personal efficacy (p < 0.05). Univariate analysis showed differences between the groups in perceptions of personal risks, side effects, and efficacy of the vaccine (p < 0.05). Multivariate analysis found that important factors influencing vaccination behavior were work place, colleagues' opinions, having a chronic disease, belief that vaccination was effective, and belief that flu can be prevented by natural ways. Numerous factors influence health professionals' decisions about influenza vaccination. Strategies to increase the ratio of vaccination among physicians and nurses should consider all of these factors to increase the likelihood of success.

Health gains and financial risk protection afforded by public financing of selected interventions in Ethiopia: an extended cost-effectiveness analysis.

PubMed

Verguet, Stéphane; Olson, Zachary D; Babigumira, Joseph B; Desalegn, Dawit; Johansson, Kjell Arne; Kruk, Margaret E; Levin, Carol E; Nugent, Rachel A; Pecenka, Clint; Shrime, Mark G; Memirie, Solomon Tessema; Watkins, David A; Jamison, Dean T

2015-05-01

The way in which a government chooses to finance a health intervention can affect the uptake of health interventions and consequently the extent of health gains. In addition to health gains, some policies such as public finance can insure against catastrophic health expenditures. We aimed to evaluate the health and financial risk protection benefits of selected interventions that could be publicly financed by the government of Ethiopia. We used extended cost-effectiveness analysis to assess the health gains (deaths averted) and financial risk protection afforded (cases of poverty averted) by a bundle of nine (among many other) interventions that the Government of Ethiopia aims to make universally available. These nine interventions were measles vaccination, rotavirus vaccination, pneumococcal conjugate vaccination, diarrhoea treatment, malaria treatment, pneumonia treatment, caesarean section surgery, hypertension treatment, and tuberculosis treatment. Our analysis shows that, per dollar spent by the Ethiopian Government, the interventions that avert the most deaths are measles vaccination (367 deaths averted per $100,000 spent), pneumococcal conjugate vaccination (170 deaths averted per $100,000 spent), and caesarean section surgery (141 deaths averted per $100,000 spent). The interventions that avert the most cases of poverty are caesarean section surgery (98 cases averted per $100,000 spent), tuberculosis treatment (96 cases averted per $100,000 spent), and hypertension treatment (84 cases averted per $100,000 spent). Our approach incorporates financial risk protection into the economic evaluation of health interventions and therefore provides information about the efficiency of attainment of both major objectives of a health system: improved health and financial risk protection. One intervention might rank higher on one or both metrics than another, which shows how intervention choice-the selection of a pathway to universal health coverage-might involve weighing up of sometimes competing objectives. This understanding can help policy makers to select interventions to target specific policy goals (ie, improved health or financial risk protection). It is especially relevant for the design and sequencing of universal health coverage to meet the needs of poor populations. Copyright © 2015 Verguet et al. Open access article published under the terms of CC BY-NC-SA. Published by .. All rights reserved.

Taking aim at novel vaccines market.

PubMed

Awasthi, Sita

2009-10-01

The World Vaccine Congress Washington 2009 was held in Chantilly, VA USA April 2O -23rd. The Vaccine congress attracted over 400 participants from across the world, including leading vaccine manufacturers, biotechs, governmental agencies, NGOs, research and academic institutes, venture capital and legal firms, contract service and equipment manufacturers. The speakers covered a wide range of topics, including the role of government and regulatory agencies, funding availability, research and development, manufacturing, packaging and post vaccine evaluations. Past vaccine development efforts have historically focused on infectious diseases. With advancements in the field of immunology, molecular biology and vaccinology, the vaccine field has begun moving in new directions. "Taking aim at novel vaccines market" session chaired by Dr. Una Ryan, Chief Executive Officer of Waltham Technologies, was focused on traditional approaches to novel targets (nosocomial infections), novel approaches to traditional targets (flu and rabies), novel approaches to novel targets (Type 1 diabetes, multiple sclerosis and smoking) and vaccines for developing markets (TB, malaria, rabies). The importance of collaborations among academic institutions, industries, and philanthropic foundations for developing markets was also emphasized.

Safety studies with the oral rabies virus vaccine strain SPBN GASGAS in the small Indian mongoose (Herpestes auropunctatus).

PubMed

Ortmann, Steffen; Vos, Ad; Kretzschmar, Antje; Walther, Nomusa; Kaiser, Christiane; Freuling, Conrad; Lojkic, Ivana; Müller, Thomas

2018-03-13

Oral vaccination of the small Indian mongoose against rabies has been suggested as a potential tool to eliminate mongoose-mediated rabies on several Caribbean islands. A recently developed oral rabies virus vaccine strain, SPBN GASGAS, has already been shown to be efficacious in this reservoir species. Since, all available oral rabies vaccines are based on replication-competent viruses and vaccine baits are distributed unsupervised in the environment, enhanced safety standards for such vaccine types are required. The results of safety studies, including overdose, repeated doses, dissemination and different routes of administration, in the target species are presented. It was shown that the construct was apathogenic, irrespective of dose and route of administration. Even when it was inoculated directly in the brain, it did not induce rabies infection. Furthermore, the vaccine strain did not spread within the target species after direct oral instillation beyond the site of entry. The vaccine strain SPBN GASGAS meets the safety requirements for live rabies virus vaccines in this target species, the small Indian mongoose.

Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines.

PubMed

Goyvaerts, Cleo; Breckpot, Karine

2015-01-01

In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.

Potency control of modified live viral vaccines for veterinary use.

PubMed

Terpstra, C; Kroese, A H

1996-04-01

This paper reviews various aspects of efficacy, and methods for assaying the potency of modified live viral vaccines. The pros and cons of parametric versus non-parametric methods for analysis of potency assays are discussed and critical levels of protection, as determined by the target(s) of vaccination, are exemplified. Recommendations are presented for designing potency assays on master virus seeds and vaccine batches.

Potency control of modified live viral vaccines for veterinary use.

PubMed

Terpstra, C; Kroese, A H

1996-01-01

This paper reviews various aspects of efficacy, and methods for assaying the potency of modified live viral vaccines. The pros and cons of parametric versus non-parametric methods for analysis of potency assays are discussed and critical levels of protection, as determined by the target(s) of vaccination, are exemplified. Recommendations are presented for designing potency assays on master virus seeds and vaccine batches.

Blocking pathogen transmission at the source: reservoir targeted OspA-based vaccines against Borrelia burgdorferi.

PubMed

Gomes-Solecki, Maria

2014-01-01

Control strategies are especially challenging for microbial diseases caused by pathogens that persist in wildlife reservoirs and use arthropod vectors to cycle amongst those species. One of the most relevant illnesses that pose a direct human health risk is Lyme disease; in the US, the Centers for Disease Control and Prevention recently revised the probable number of cases by 10-fold, to 300,000 cases per year. Caused by Borrelia burgdorferi, Lyme disease can affect the nervous system, joints and heart. No human vaccine is approved by the Food and Drug Administration. In addition to novel human vaccines, new strategies for prevention of Lyme disease consist of pest management interventions, vector-targeted vaccines and reservoir-targeted vaccines. However, even human vaccines can not prevent Lyme disease expansion into other geographical areas. The other strategies aim at reducing tick density and at disrupting the transmission of B. burgdorferi by targeting one or more key elements that maintain the enzootic cycle: the reservoir host and/or the tick vector. Here, I provide a brief overview of the application of an OspA-based wildlife reservoir targeted vaccine aimed at reducing transmission of B. burgdorferi and present it as a strategy for reducing Lyme disease risk to humans.

Blocking pathogen transmission at the source: reservoir targeted OspA-based vaccines against Borrelia burgdorferi

PubMed Central

Gomes-Solecki, Maria

2014-01-01

Control strategies are especially challenging for microbial diseases caused by pathogens that persist in wildlife reservoirs and use arthropod vectors to cycle amongst those species. One of the most relevant illnesses that pose a direct human health risk is Lyme disease; in the US, the Centers for Disease Control and Prevention recently revised the probable number of cases by 10-fold, to 300,000 cases per year. Caused by Borrelia burgdorferi, Lyme disease can affect the nervous system, joints and heart. No human vaccine is approved by the Food and Drug Administration. In addition to novel human vaccines, new strategies for prevention of Lyme disease consist of pest management interventions, vector-targeted vaccines and reservoir-targeted vaccines. However, even human vaccines can not prevent Lyme disease expansion into other geographical areas. The other strategies aim at reducing tick density and at disrupting the transmission of B. burgdorferi by targeting one or more key elements that maintain the enzootic cycle: the reservoir host and/or the tick vector. Here, I provide a brief overview of the application of an OspA-based wildlife reservoir targeted vaccine aimed at reducing transmission of B. burgdorferi and present it as a strategy for reducing Lyme disease risk to humans. PMID:25309883

Barriers and facilitators to HPV vaccination of young women in high-income countries: a qualitative systematic review and evidence synthesis

PubMed Central

2014-01-01

Background Vaccination against Human Papillomavirus (HPV) is recommended for adolescent young women prior to sexual debut to reduce cervical cancer related mortality and morbidity. Understanding factors affecting decision-making of HPV vaccination of young women is important so that effective interventions can be developed which address barriers to uptake in population groups less likely to receive the HPV vaccine. Methods We undertook a qualitative systematic review and evidence synthesis to examine decision-making relating to the HPV vaccination of young women in high-income countries. A comprehensive search of databases from inception to March 2012 was undertaken to identify eligible studies reporting the perspectives of key stakeholders including policy makers, professionals involved in programme, parents, and young women. Factors affecting uptake of the vaccine were examined at different levels of the socio-ecological model (policy, community, organisational, interpersonal and intrapersonal). Results Forty-one studies were included. Whether young women receive the HPV vaccine is strongly governed by the decisions of policy makers, healthcare professionals, and parents. These decisions are shaped by: financial considerations; social norms and values relating to sexual activity, and; trust in vaccination programmes and healthcare providers. Financial constraints may be overcome through universal healthcare systems offering the HPV vaccine free at the point of delivery. In the healthcare setting, judgements by healthcare professionals about whether to recommend the vaccine may restrict a young woman’s access to the vaccine irrespective of her own beliefs and preferences. Parents may decide not to allow their daughters to be vaccinated, based on cultural or religious perceptions about sexual activity. Conclusions Barriers to the uptake of the HPV vaccine have implications for young women’s future sexual, physical and reproductive health. Interventions to address barriers to uptake of the vaccine should target appropriate, and multiple, levels of the socio-ecological model. Issues of trust require clear, accessible, and sometimes culturally appropriate, information about the HPV vaccination programme. Although young women are central to the HPV vaccination programme, their views are underrepresented in the qualitative literature. Future research should consider young women’s perceptions of, and involvement in, consent and decision-making. PMID:25004868

Annual public health and economic benefits of seasonal influenza vaccination: a European estimate.

PubMed

Preaud, Emmanuelle; Durand, Laure; Macabeo, Bérengère; Farkas, Norbert; Sloesen, Brigitte; Palache, Abraham; Shupo, Francis; Samson, Sandrine I

2014-08-07

Vaccination is currently the most effective means of preventing influenza infection. Yet evidence of vaccine performance, and the impact and value of seasonal influenza vaccination across risk groups and between seasons, continue to generate much discussion. Moreover, vaccination coverage is below recommended levels. A model was generated to assess the annual public health benefits and economic importance of influenza vaccination in 5 WHO recommended vaccination target groups (children 6 - 23 months of age; persons with underlying chronic health conditions; pregnant women; health care workers; and, the elderly, 65 years of age) in 27 countries of the European Union. Model estimations were based on standard calculation methods, conservative assumptions, age-based and country-specific data. Out of approximately 180 million Europeans for whom influenza vaccination is recommended, only about 80 million persons are vaccinated. Seasonal influenza vaccination currently prevents an annual average of between 1.6 million and 2.1 million cases of influenza, 45,300 to 65,600 hospitalizations, and 25,200 to 37,200 deaths. To reach the 75% vaccination coverage target set by the EU Council Recommendation in 2009, an additional 57.4 million person would need to be vaccinated in the elderly and other risk groups. By achieving the 75% target rate set in EU-27 countries, average annual influenza- related events averted would increase from current levels to an additional +1.6 to +1.7 million cases, +23,800 to +31,400 hospitalization, +9,800 to +14,300 deaths, +678,500 to +767,800 physician visits, and +883,800 to +1,015,100 lost days of work yearly. Influenza-related costs averted because of vaccination would increase by an additional + €190 to + €226 million yearly, in vaccination target groups. Full implementation of current influenza vaccination recommendations of 75% vaccination coverage rate (VCR) in Europe by the 2014-2015 influenza season could immediately reduce an important public health and economic burden.

Toward measles elimination in Bahrain--a Middle East country experience.

PubMed

Jawad, Jaleela S; Al-Sayyad, Adel S; Sataih, Fathiya; Naouri, Boubker; Alexander, James P

2011-07-01

Measles was a leading cause of infant and child morbidity and mortality in Bahrain before the introduction of measles vaccine in 1974. With the establishment of the Expanded Program on Immunization (EPI) in 1981 and the introduction of a second dose of measles vaccine in 1985, coverage for first and second doses of measles vaccine increased to 94% by 1997 and has been sustained >97% since 2001. Measles, mumps, and rubella (MMR) immunization campaigns targeting 12-year-old students were conducted annually during 1998-2006 and achieved coverage of >95%. As a result, the incidence of measles in Bahrain has declined markedly over the past 4 decades, to 2.7 cases per million persons in 2009. Recent confirmed measles cases have occurred sporadically, in undervaccinated children or in infants too young or adults too old to receive measles vaccine. Bahrain has made significant progress toward measles elimination by sustaining high immunization coverage and strengthening case-based measles surveillance activities. Further success will depend on improved identification and immunization of undervaccinated expatriate workers and their families. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.

Universal paid leave increases influenza vaccinations among employees in the U.S.

PubMed

Wilson, Fernando A; Wang, Yang; Stimpson, Jim P

2014-05-01

We predict the impact of paid leave in increasing influenza vaccinations for employees, thus decreasing workdays lost and healthcare visits resulting from infection. Nationally representative data from the 2006-2010 Medical Expenditure Panel Survey were used. We examined working adults aged 18 and above (N=51,471). Logistic regression measured the association of paid leave with flu vaccination. We predicted the impact on labor and healthcare markets if universal paid leave were provided. The proportion of workers receiving vaccination annually was higher for those with paid leave versus without paid leave (34.0% vs. 21.0%, P<0.001). Adjusted odds of having a vaccination increased with paid leave vs. without paid leave (OR=1.42, CI: 1.31-1.53). Universal paid leave is predicted to increase vaccinations by 1.6 million, resulting in 63.8 thousand fewer absences from work and 18.2 thousand fewer healthcare visits for the flu annually. Our study suggests that employees without paid leave are significantly less likely to have had a flu vaccination. Expanding paid leave could substantially increase flu vaccination, resulting in fewer workdays lost to influenza and savings in healthcare costs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Current and future effects of varicella and herpes zoster vaccination in Germany - Insights from a mathematical model in a country with universal varicella vaccination.

PubMed

Horn, Johannes; Karch, André; Damm, Oliver; Kretzschmar, Mirjam E; Siedler, Anette; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Hengel, Hartmut; Greiner, Wolfgang; Mikolajczyk, Rafael T

2016-07-02

Varicella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age-classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the model's results provide valuable insights that support decision-making regarding national VZV vaccination strategies.

Targeted vaccination in healthy school children - Can primary school vaccination alone control influenza?

PubMed

Thorrington, Dominic; Jit, Mark; Eames, Ken

2015-10-05

The UK commenced an extension to the seasonal influenza vaccination policy in autumn 2014 that will eventually see all healthy children between the ages of 2-16 years offered annual influenza vaccination. Models suggest that the new policy will be both highly effective at reducing the burden of influenza as well as cost-effective. We explore whether targeting vaccination at either primary or secondary schools would be more effective and/or cost-effective than the current strategy. An age-structured deterministic transmission dynamic SEIR-type mathematical model was used to simulate a national influenza outbreak in England. Costs including GP consultations, hospitalisations due to influenza and vaccinations were compared to potential gains in quality-adjusted life years achieved through vaccinating healthy children. Costs and benefits of the new JCVI vaccination policy were estimated over a single season, and compared to the hypothesised new policies of targeted and heterogeneous vaccination. All potential vaccination policies were highly cost-effective. Influenza transmission can be eliminated for a particular season by vaccinating both primary and secondary school children, but not by vaccinating only one group. The most cost-effective policy overall is heterogeneous vaccination coverage with 48% uptake in primary schools and 34% in secondary schools. The Joint Committee on Vaccination and Immunisation can consider a modification to their policy of offering seasonal influenza vaccinations to all healthy children of ages 2-16 years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human Vaccines & Immunotherapeutics: News

PubMed Central

Riedmann, Eva M

2013-01-01

Vaccinating boys against HPV to reduce cancer rates across the sexes New melanoma vaccine contains natural product from marine sponges Impact of Hib conjugate vaccines in developing countries Electronic Health Records to keep track of immunization status Pregnant women urged to get whooping cough vaccination New nano-coating developed to preserve vaccines Alternative approach to creating a universal flu vaccine New modular vaccine design: MAPS technology PMID:24051387

Mumps Outbreak Among a Highly Vaccinated University Community-New York City, January-April 2014.

PubMed

Patel, Leena N; Arciuolo, Robert J; Fu, Jie; Giancotti, Francesca R; Zucker, Jane R; Rakeman, Jennifer L; Rosen, Jennifer B

2017-02-15

On 14 January 2014, a vaccinated student presented with parotitis. Mumps immunoglobulin M (IgM) testing was negative and reverse-transcription polymerase chain reaction (RT-PCR) testing was not performed, resulting in a missed diagnosis and the start of an outbreak at a New York City (NYC) university. Mumps case investigations included patient interviews, medical records review, and laboratory testing including mumps serology and RT-PCR. Case patients were considered linked to the outbreak if they attended or had epidemiologic linkage to the university. Epidemiologic, clinical, and laboratory data for outbreak cases residing in NYC were analyzed. Fifty-six NYC residents with mumps were identified with onset between 12 January and 30 April 2014. Fifty-three cases (95%) were university students, 1 (2%) was a staff member, and 2 (4%) had epidemiologic links to the university. The median age was 20 years (range 18-37 years). All cases had parotitis. Three cases were hospitalized, including 1 of 2 cases with orchitis. Fifty-four (96%) cases had received ≥1 mumps-containing vaccine, 1 (2%) was unvaccinated due to religious exemption, and 1 (2%) had unknown vaccination status. Two of the 44 (5%) cases tested by serology were mumps IgM positive, and 27 of the 40 (68%) tested by RT-PCR were positive. Mumps outbreaks can occur in highly vaccinated populations. Mumps should be considered in patients with parotitis regardless of vaccination status. RT-PCR is the preferred testing method; providers should not rely on IgM testing alone. High vaccination coverage and control measures likely limited the extent of the outbreak. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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

Development of a community pharmacy human papillomavirus vaccine program for underinsured university students along the United States/Mexico border.

PubMed

Navarrete, Jacquelyn P; Padilla, Margie E; Castro, Louise P; Rivera, José O

2014-01-01

To describe the development and implementation of a human papillomavirus (HPV) vaccine patient assistance program (PAP) for university students, and to acquire information on the number who accessed the program and completed the series. University of Texas at El Paso University Student Health Clinic Pharmacy, Fall 2011-Spring 2014. A community pharmacy located within the university student health clinic providing services to an underinsured student population. Existing evidence shows the benefit of using PAP in community pharmacies but is nonspecific regarding the use of PAP for vaccines in an uninsured and underinsured Hispanic student population. The implementation of this unique HPV vaccine program in a community setting aims to increase awareness, access, and rates. Primary measures included results from a needs-assessment questionnaire that were used to implement the HPV vaccine program. After implementation, utilization data were collected on the number of students who qualified and enrolled in the HPV PAP and the number of students who completed the HPV series. The preliminary data from a needs assessment indicated that a majority (72.1%, n = 80) of students did not understand how HPV is transmitted. A total of 89 students qualified for PAP. The majority were women (81%). A total of 71 students (79.8%) received their second dose and 43 (48.3%) completed the series. Although pharmacists continue to provide vaccine services, minorities such as the Hispanic population continue to be underimmunized. Students may not be taking the proper precautions to prevent the acquisition of HPV. For these reasons services such as this HPV vaccine program are warranted. Pharmacists need to continue to educate and advocate on the importance of vaccines and how they prevent disease.

New generation of oral mucosal vaccines targeting dendritic cells.

PubMed

Owen, Jennifer L; Sahay, Bikash; Mohamadzadeh, Mansour

2013-12-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including Bacillus anthracis in experimental models of disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

A novel subnucleocapsid nanoplatform for mucosal vaccination against influenza virus that targets the ectodomain of matrix protein 2.

PubMed

Hervé, Pierre-Louis; Raliou, Mariam; Bourdieu, Christiane; Dubuquoy, Catherine; Petit-Camurdan, Agnès; Bertho, Nicolas; Eléouët, Jean-François; Chevalier, Christophe; Riffault, Sabine

2014-01-01

In this study, subnucleocapsid nanorings formed by the recombinant nucleoprotein (N) of the respiratory syncytial virus were evaluated as a platform to anchor heterologous antigens. The ectodomain of the influenza virus A matrix protein 2 (M2e) is highly conserved and elicits protective antibodies when it is linked to an immunogenic carrier, making it a promising target to develop universal influenza vaccines. In this context, one or three M2e copies were genetically linked to the C terminus of N to produce N-M2e and N-3M2e chimeric recombinant nanorings. Mice were immunized intranasally with N-M2e or N-3M2e or with M2e or 3M2e control peptides. N-3M2e-vaccinated mice showed the strongest mucosal and systemic antibody responses. These mice presented a reduced viral load and minor weight loss, and all survived upon challenge with influenza virus A/PR8/34 (H1N1) (PR8). We compared the intranasal route to the subcutaneous route of N-3M2e immunization. Only the intranasal route induced a strong local IgA response and led to the protection of mice upon challenge. Finally, we demonstrated that the induction of anti-M2e antibodies by N-3M2e is not impaired by preexisting anti-N immunity. Overall, these results show that the N nanoring is a potent carrier for mucosal delivery of vaccinal antigens.

A Novel Subnucleocapsid Nanoplatform for Mucosal Vaccination against Influenza Virus That Targets the Ectodomain of Matrix Protein 2

PubMed Central

Hervé, Pierre-Louis; Raliou, Mariam; Bourdieu, Christiane; Dubuquoy, Catherine; Petit-Camurdan, Agnès; Bertho, Nicolas; Eléouët, Jean-François

2014-01-01

In this study, subnucleocapsid nanorings formed by the recombinant nucleoprotein (N) of the respiratory syncytial virus were evaluated as a platform to anchor heterologous antigens. The ectodomain of the influenza virus A matrix protein 2 (M2e) is highly conserved and elicits protective antibodies when it is linked to an immunogenic carrier, making it a promising target to develop universal influenza vaccines. In this context, one or three M2e copies were genetically linked to the C terminus of N to produce N-M2e and N-3M2e chimeric recombinant nanorings. Mice were immunized intranasally with N-M2e or N-3M2e or with M2e or 3M2e control peptides. N-3M2e-vaccinated mice showed the strongest mucosal and systemic antibody responses. These mice presented a reduced viral load and minor weight loss, and all survived upon challenge with influenza virus A/PR8/34 (H1N1) (PR8). We compared the intranasal route to the subcutaneous route of N-3M2e immunization. Only the intranasal route induced a strong local IgA response and led to the protection of mice upon challenge. Finally, we demonstrated that the induction of anti-M2e antibodies by N-3M2e is not impaired by preexisting anti-N immunity. Overall, these results show that the N nanoring is a potent carrier for mucosal delivery of vaccinal antigens. PMID:24155388

Cholera cases cluster in time and space in Matlab, Bangladesh: implications for targeted preventive interventions.

PubMed

Debes, Amanda K; Ali, Mohammad; Azman, Andrew S; Yunus, Mohammad; Sack, David A

2016-12-01

: Cholera remains a serious public health threat in Asia, Africa and in parts of the Americas. Three World health Organization (WHO) pre-qualified oral cholera vaccines are now available but their supply is limited, so current supplies must be administered strategically. This requires an improved understanding of disease transmission and control strategies. : We used demographics and disease surveillance data collected from 1991 to 2000 in Matlab, Bangladesh, to estimate the spatial and temporal extent of the zone of increased risk around cholera cases. Specifically, we compare the cholera incidence among individuals living close to cholera cases with that among individuals living close to those without medically-attended cholera in this rural endemic setting. : Those living within 50 m of a confirmed cholera case had 36 times (95% confidence interval: 23-56) the risk of becoming a cholera case in the first 3 days (after case presentation) compared with risk elsewhere in the community. The relative risk gradually declined in space and time, but remained significantly high up to 450 me away within 3 days of case presentation, and up to 150 m away within 23 days from the date of presentation of the case. : These findings suggest that, if conducted rapidly, vaccinating individuals living close to a case (ring vaccination) could be an efficient and effective strategy to target vaccine to a high-risk population in an endemic setting. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Malaria vaccines: past, present and future.

PubMed

von Seidlein, Lorenz; Bejon, Philip

2013-12-01

The currently available malaria control tools have allowed malaria elimination in many regions but there remain many regions where malaria control has made little progress. A safe and protective malaria vaccine would be a huge asset for malaria control. Despite the many challenges, efforts continue to design and evaluate malaria vaccine candidates. These candidates target different stages in the life cycle of Plasmodia. The most advanced vaccine candidates target the pre-erythrocytic stages in the life cycle of the parasite and include RTS,S/AS01, which has progressed through clinical development to the stage that it may be licensed in 2015. Attenuated whole-parasite vaccine candidates are highly protective, but there are challenges to manufacture and to administration. Cellular immunity is targeted by the prime-boost approach. Priming vectors trigger only modest responses but these are focused on the recombinant antigen. Boosting vectors trigger strong but broad non-specific responses. The heterologous sequence produces strong immunological responses to the recombinant antigen. Candidates that target the blood stages of the parasite have to result in an immune response that is more effective than the response to an infection to abort or control the infection of merozoites and hence disease. Finally, the sexual stages of the parasite offer another target for vaccine development, which would prevent the transmission of malaria. Today it seems unlikely that any candidate targeting a single antigen will provide complete protection against an organism of the complexity of Plasmodium. A systematic search for vaccine targets and combinations of antigens may be a more promising approach.

Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG.

PubMed

Reglinski, Mark; Lynskey, Nicola N; Choi, Yoon Jung; Edwards, Robert J; Sriskandan, Shiranee

2016-04-01

Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin. Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease. Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release. Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG

PubMed Central

Reglinski, Mark; Lynskey, Nicola N.; Choi, Yoon Jung; Edwards, Robert J.; Sriskandan, Shiranee

2016-01-01

Summary Objectives Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin. Methods Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease. Results Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release. Conclusion Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria. PMID:26880087

Benefits of pharmacist-led flu vaccination services in community pharmacy.

PubMed

Kirkdale, C L; Nebout, G; Megerlin, F; Thornley, T

2017-01-01

Seasonal influenza is a major cause of excess winter deaths and increased hospital admissions. There is a high level of economic burden associated with the infection. Although vaccination targets have been set to tackle this international issue, many countries struggle to reach these coverage targets for their at-risk populations using traditional delivery methods. Traditional providers include family doctors and nurses; however, pharmacist-led influenza vaccination has become a more commonly utilised aid to support vaccination targets. Community pharmacies are convenient and widely accessible and evaluations consistently demonstrate that patients are satisfied with pharmacist-led vaccinations. Allowing community pharmacists to administer influenza vaccination as an alternative option for delivery helps to increase the coverage rate of vaccination. In addition, commissioning community pharmacists to provide this service has been shown to contribute to achieving targets for those at-risk. Pharmacist-led influenza vaccination services can create value for payors and reduce pressure on health systems. This review aims to demonstrate the success of pharmacy-led influenza vaccinations, and the impact it has had in driving up immunisation rates within other countries. Experiences of countries such as England, Portugal and the United States provide evidence to demonstrate the benefit to both the patient and the health system. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Integrating epidemiology, psychology, and economics to achieve HPV vaccination targets.

PubMed

Basu, Sanjay; Chapman, Gretchen B; Galvani, Alison P

2008-12-02

Human papillomavirus (HPV) vaccines provide an opportunity to reduce the incidence of cervical cancer. Optimization of cervical cancer prevention programs requires anticipation of the degree to which the public will adhere to vaccination recommendations. To compare vaccination levels driven by public perceptions with levels that are optimal for maximizing the community's overall utility, we develop an epidemiological game-theoretic model of HPV vaccination. The model is parameterized with survey data on actual perceptions regarding cervical cancer, genital warts, and HPV vaccination collected from parents of vaccine-eligible children in the United States. The results suggest that perceptions of survey respondents generate vaccination levels far lower than those that maximize overall health-related utility for the population. Vaccination goals may be achieved by addressing concerns about vaccine risk, particularly those related to sexual activity among adolescent vaccine recipients. In addition, cost subsidizations and shifts in federal coverage plans may compensate for perceived and real costs of HPV vaccination to achieve public health vaccination targets.

Population-Level Persistence of Immunity 2 Years After the PsA-TT Mass-Vaccination Campaign in Mali.

PubMed

Basta, Nicole E; Borrow, Ray; Berthe, Abdoulaye; Dembélé, Awa Traoré Eps; Onwuchekwa, Uma; Townsend, Kelly; Boukary, Rahamatou M; Mabey, Lesley; Findlow, Helen; Bai, Xilian; Sow, Samba O

2015-11-15

In 2010, Africa's first preventive meningococcal mass vaccination campaign was launched using a newly developed Neisseria meningitidis group A (NmA) polysaccharide-tetanus toxoid conjugate vaccine, PsA-TT (MenAfriVac), designed specifically for the meningitis belt. Given PsA-TT's recent introduction, the duration of protection against meningococcal group A is unknown. We conducted a household-based, age-stratified seroprevalence survey in Bamako, Mali, in 2012, 2 years after the vaccination campaign targeted all 1- to 29-year-olds. Randomly selected participants who had been eligible for PsA-TT provided a blood sample and responded to a questionnaire. Sera were analyzed to assess NmA-specific serum bactericidal antibody titers using rabbit complement (rSBA) and NmA-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. The proportion of participants putatively protected and the age group- and sex-specific rSBA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were determined. Two years postvaccination, nearly all of the 800 participants (99.0%; 95% confidence interval [CI], 98.3%-99.7%) maintained NmA-specific rSBA titers ≥8, the accepted threshold for protection; 98.6% (95% CI, 97.8%-99.4%) had titers ≥128, and 89.5% (95% CI, 87.4%-91.6%) had titers ≥1024. The rSBA GMTs were significantly higher in females than in males aged <18 years at vaccination (P < .0001). NmA-specific IgG levels ≥2 µg/mL were found in 88.5% (95% CI, 86.3%-90.7%) of participants. Two years after PsA-TT introduction, a very high proportion of the population targeted for vaccination maintains high antibody titers against NmA. Assessing the duration of protection provided by PsA-TT is a priority for implementing evidence-based vaccination strategies. Representative, population-based seroprevalence studies complement clinical trials and provide this key evidence. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

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.

Rotavirus vaccines in Israel: Uptake and impact

PubMed Central

Muhsen, Khitam; Cohen, Daniel

2017-01-01

ABSTRACT We present an overview of the impact of universal rotavirus immunization with the pentavalent vaccine, RotaTeq, which was introduced in Israel in 2010. The vaccine is given free of charge at age 2, 4 and 6 months, with an 80% coverage that was shortly achieved during the universal immunization period. Compared to pre-universal immunization years (2008–2010), a reduction of 66–68% in the incidence of rotavirus gastroenteritis (RVGE) hospitalizations was observed in 2011–2015 among children aged 0–23 months in central and northern Israel. In southern Israel a reduction of 80–88% in RVGE hospital visit rate was found among Jewish children aged 0–23 months in 2011–2013. Among Bedouins, the respective decline was 62–75%. A significant reduction of 59% was also observed in RVGE clinic visits, presumably representing less severe illness. Indirect benefit was evident in children aged 24–59 months who were ineligible for universal immunization. Vaccine effectiveness against RVGE hospitalization was estimated at 86% in children aged 6–23 months. Changes in the circulating rotavirus genotypes occurred but the contribution of vaccine induced immune pressure is unclear. Universal rotavirus immunization was followed by an impressive decrease in the burden of RVGE in young children in Israel, likely attributed to good vaccine coverage and effectiveness. PMID:28281866

Strategies to induce broadly protective antibody responses to viral glycoproteins.

PubMed

Krammer, F

2017-05-01

Currently, several universal/broadly protective influenza virus vaccine candidates are under development. Many of these vaccines are based on strategies to induce protective antibody responses against the surface glycoproteins of antigenically and genetically diverse influenza viruses. These strategies might also be applicable to surface glycoproteins of a broad range of other important viral pathogens. Areas covered: Common strategies include sequential vaccination with divergent antigens, multivalent approaches, vaccination with glycan-modified antigens, vaccination with minimal antigens and vaccination with antigens that have centralized/optimized sequences. Here we review these strategies and the underlying concepts. Furthermore, challenges, feasibility and applicability to other viral pathogens are discussed. Expert commentary: Several broadly protective/universal influenza virus vaccine strategies will be tested in humans in the coming years. If successful in terms of safety and immunological readouts, they will move forward into efficacy trials. In the meantime, successful vaccine strategies might also be applied to other antigenically diverse viruses of concern.

Vaccines for preventing influenza in healthy adults.

PubMed

Demicheli, V; Rivetti, D; Deeks, J J; Jefferson, T O

2004-01-01

Three different types of influenza vaccines are currently produced worldwide. None is traditionally targeted to healthy adults. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has negative impact on the vaccines acceptance and uptake. To assess the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004) which contains the Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January 1966 to December 2003); and EMBASE (1990 to December 2003). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. Two reviewers independently assessed trial quality and extracted data. Twenty five reports of studies involving 59,566 people were included. The recommended live aerosol vaccines reduced the number of cases of serologically confirmed influenza by 48% (95% confidence interval (CI) 24% to 64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy of 70% (95% CI 56% to 80%). The yearly recommended vaccines had low effectiveness against clinical influenza cases: 15%(95% CI 8% to 21%) and 25% (95% CI 13% to 35%) respectively. Overall the percentage of participants experiencing clinical influenza decreased by 6%. Use of the vaccine significantly reduced time off work but only by 0.16 days for each influenza episode (95% CI 0.04 to 0.29 days); Analysis of vaccines matching the circulating strain gave higher estimates of efficacy, whilst inclusion of all other vaccines reduced the efficacy. Influenza vaccines are effective in reducing serologically confirmed cases of influenza. However, they are not as effective in reducing cases of clinical influenza and number of working days lost. Universal immunisation of healthy adults is not supported by the results of this review.

Emerging Vaccine Therapy Approaches for Prostate Cancer

PubMed Central

Sonpavde, Guru; Slawin, Kevin M; Spencer, David M; Levitt, Jonathan M

2010-01-01

Prostate cancer vaccines attempt to induce clinically relevant, cancer-specific systemic immune responses in patients with prostate cancer and represent a new class of targeted, nontoxic therapies. With a growing array of vaccine technologies in preclinical or clinical development, autologous antigen-presenting cell vaccines loaded with the antigen, prostate acid phosphatase, and poxvirus vaccines targeting prostate-specific antigen have recently demonstrated a significant survival benefit in randomized trials of patients with metastatic castration-resistant prostate cancer, whereas others have failed to demonstrate any benefit. The combination of vaccines with chemotherapy, radiotherapy, and other biologic agents is also being evaluated. Efforts to optimize vaccine approaches and select ideal patient populations need to continue to build on these early successes. PMID:20428291

Preventive health pamphlets in the emergency department.

PubMed

Berger, P; Luskin, M; Krishel, S

1998-01-01

We conducted a prospective clinical trial to determine the effectiveness of an emergency department informational pamphlet in improving patients' compliance with recommendations that they receive Pap smears, mammograms, and a pneumococcal vaccination. Informational pamphlets were distributed to 1,000 consecutive patients who presented to a university-affiliated emergency department (ED). The pamphlet contained information stating the indications for obtaining routine Pap smears, mammograms, and a pneumococcal vaccination. Target individuals were women 18 years and older and men 65 years and older. Target patients were called approximately 2 months after their ED visits to obtain follow-up data. There were 464 target patients obtained from the 1,000 pamphlets distributed (409 female/55 male), and 68% (316) of the 464 were contacted by telephone for follow-up data. Significantly more women than men had read the pamphlet (62% vs. 8%). Of the women contacted (279), 31.9% (89) were not up to date (UTD) with Pap smears, and 11.2% (10) stated that they had scheduled an appointment for a Pap smear; 14.5% (11) of the women were not UTD with mammograms, and none had scheduled an appointment to receive care. Of the patients over age 65, 67% were not UTD with a pneumococcal vaccination, and no appointments were scheduled to obtain one. We conclude that a significant number of patients who present to this ED are in need of preventive health care. Emergency department informational pamphlets may have a role in improving Pap smear compliance. Women may be more likely then men to read informational pamphlets distributed in the ED.

Use of pre-travel vaccine-preventable disease serology as a screening tool to identify patients in need of pre-travel vaccination: a retrospective audit.

PubMed

Turner, David P; McGuinness, Sarah L; Cohen, Jonathan; Waring, Lynette J; Leder, Karin

2017-05-01

Vaccination is a safe and effective public health intervention that not only protects individual travellers from vaccine-preventable diseases (VPDs), but prevents them from becoming a source of disease in their destination and on their return. Obtaining an accurate vaccination history from travellers during a pre-travel review can be difficult; serology may be used to identify patients who are non-immune to specific diseases in order to guide vaccination requirements. Clinically relevant data about the usefulness of serology in this setting are lacking. We performed a retrospective audit of pre-travel VPD serology requested by practitioners of a busy community-based travel clinic. All serological results for measles, mumps, rubella, varicella zoster virus, hepatitis A and B requested over a 5-year period were extracted and analysed. Results were stratified by gender and year of birth and compared using Stata. Four thousand four hundred and fifty-one serological assays from 1445 individual were assessed. Overall, 47% of patients tested had at least one negative serological result. High rates of seropositivity for measles, mumps and rubella were seen in those born prior to 1966 but >10% of travellers born after 1966 lacked serological evidence of protection against these diseases. Hepatitis A and B serological results revealed broadly lower rates of immunity in our community likely reflecting the absence of these vaccines from historical vaccine protocols. Serology can be a useful tool in the identification of non-immune travellers to enable targeted vaccination prior to travel. We recommend that travel health clinicians assess patients' vaccination and infection histories, and strongly consider serology or vaccination where there is doubt about immunity. This will help protect the traveller and prevent importation of disease into destination or home communities. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

The prospects and challenges of universal vaccines for influenza

PubMed Central

Subbarao, Kanta; Matsuoka, Yumiko

2013-01-01

Vaccination is the most effective way to reduce the impact of epidemic as well as pandemic influenza. However, the licensed inactivated influenza vaccine induces strain-specific immunity and must be updated annually. When novel viruses appear, matched vaccines are not likely to be available in time for the first wave of a pandemic. Yet, the enormous diversity of influenza A viruses in nature makes it impossible to predict which subtype or strain will cause the next pandemic. Several recent scientific advances have generated renewed enthusiasm and hope for universal vaccines that will induce broad protection from a range of influenza viruses. PMID:23685068

ADVICE for a healthier life: Adult Vaccination Campaign in Europe.

PubMed

Ozisik, Lale; Tanriover, Mine Durusu; Rigby, Shirley; Unal, Serhat

2016-09-01

Immunization is one of the most effective public health measures to prevent disease. Despite relatively good vaccination rates in childhood in many parts of the world, vaccines to prevent diseases are underused in the adult population and adult vaccination rates are still far below the target. The European Federation of Internal Medicine (EFIM), declared that 'internal medicine must focus on better care for individuals, better health care for populations and lower costs'. Adult vaccination is a good example of a public health initiative aimed at reducing morbidity and mortality, but awareness of the need for adult vaccination and uptake of the programs across Europe is variable. The Adult Vaccination Campaign in Europe (ADVICE) was developed with an aim to raise awareness for adult vaccination and to understand the dynamics of the vaccination practices and the possible barriers against achieving targeted vaccination rates in Europe. In order to reach vaccination targets, we need evidence based, up to date guidelines; recommendations at national and international levels; surveillance for vaccination rates; and opportunities to provide vaccines more readily. Leadership at a European level and a firm research and action agenda are crucial. The European Federation of Internal Medicine can take the lead as it declared its interest on 'better care for individuals, better health care for populations'. Hence, we consider ADVICE a very timely and very valuable initiative to draw a roadmap to improve adult vaccination rates in Europe. Copyright © 2016. Published by Elsevier B.V.

A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma.

PubMed

Shibao, Shunsuke; Ueda, Ryo; Saito, Katsuya; Kikuchi, Ryogo; Nagashima, Hideaki; Kojima, Atsuhiro; Kagami, Hiroshi; Pareira, Eriel Sandika; Sasaki, Hikaru; Noji, Shinobu; Kawakami, Yutaka; Yoshida, Kazunari; Toda, Masahiro

2018-04-20

Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas. Eight patients received intranodal vaccinations weekly at a dose of 2mg/kg bodyweight 8 times. T-lymphocyte responses against VEGF receptor (VEGFR) epitopes were assessed by enzyme linked immunosorbent spot assays. This treatment was well-tolerated in patients. The first four vaccines induced positive immune responses against at least one of the targeted VEGFR epitopes in the peripheral blood mononuclear cells in 87.5% of patients. The median overall survival time in all patients was 15.9 months. Two achieved progression-free status lasting at least 6 months. Two patients with recurrent GBM demonstrated stable disease. Plasma IL-8 level was negatively correlated with overall survival. These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas.

Rotavirus genotypes in Malaysia and Universal rotavirus vaccination

PubMed Central

Lee, Way Seah; Lim, Benjamin Tze Ying; Chai, Pei Fan; Kirkwood, Carl D.; Lee, Jimmy Kok Foo

2012-01-01

Group A rotavirus (RV-A) genotypes isolated in Malaysia was studied to estimate the effectiveness of a universal RV-A vaccination in Malaysia. A simple mathematical model was used, with input from a two-year, two-center, prospective study on hospitalization of RV-A gastroenteritis (RVGE) in young children, published data on RV-A hospitalizations and genotypes, mortality on childhood GE and published genotype-specific efficacy data on two RV-A vaccines. Assuming a 95% vaccine coverage, the overall projected effectiveness was 75.7 to 88.1% for Rotateq® and 78.7 to 90.6% for Rotarix® against RVGE-related hospitalizations. The projected annual reduction in RVGE-related deaths was 27 to 32 deaths (from 34 deaths) for Rotateq® and 28 to 32 deaths annually forRotarix®. A universal RV-A vaccine is efficacious in reducing RVGE-related hospitalizations and mortality in Malaysia. PMID:23022710

Universal influenza vaccines, a dream to be realized soon.

PubMed

Zhang, Han; Wang, Li; Compans, Richard W; Wang, Bao-Zhong

2014-04-29

Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for the development of universal influenza vaccines capable of conferring broad cross-protection against multiple subtypes of influenza A viruses. Facilitated by the advancement in modern molecular biology, delicate antigen design becomes one of the most effective factors for fulfilling such goals. Conserved epitopes residing in virus surface proteins including influenza matrix protein 2 and the stalk domain of the hemagglutinin draw general interest for improved antigen design. The present review summarizes the recent progress in such endeavors and also covers the encouraging progress in integrated antigen/adjuvant delivery and controlled release technology that facilitate the development of an affordable universal influenza vaccine.

[Anti-hepatitis B surface antigen titres in vaccinated dentistry students at Damascus University].

PubMed

Srour, I H; Mashlah, A

2012-06-01

Dental practice carries considerable danger for acquiring bloodborne pathogens such as hepatitis B virus (HBV). Vaccination against this virus is an important approach to reducing the infection. Post-vaccination test to confirm the seroconversion is important also. Over the period 1 March-31 May 2010, we assessed the efficacy of HBV vaccination among 91 fourth-year dental students at Damascus University, who were vaccinated under the mandatory Faculty of Dentistry programme. Anti-HBsAg antibody titres were determined in the blood samples using an enzyme immunoassay to measure; > or = 10 IU/mm was considered an adequate response titer. Seven of the 91 dentistry students (7.7%) had anti-HBs antibody titre < 10 mlU/mL. The frequency of unresponsiveness was significantly higherwith smoking (P = 0.012) and alcohol consumption (P = 0.014). Anti-HBs test should be included in routine immunization services of the School of Dentistry at Damascus University.

Universal Influenza Vaccines, a Dream to Be Realized Soon

PubMed Central

Zhang, Han; Wang, Li; Compans, Richard W.; Wang, Bao-Zhong

2014-01-01

Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for the development of universal influenza vaccines capable of conferring broad cross-protection against multiple subtypes of influenza A viruses. Facilitated by the advancement in modern molecular biology, delicate antigen design becomes one of the most effective factors for fulfilling such goals. Conserved epitopes residing in virus surface proteins including influenza matrix protein 2 and the stalk domain of the hemagglutinin draw general interest for improved antigen design. The present review summarizes the recent progress in such endeavors and also covers the encouraging progress in integrated antigen/adjuvant delivery and controlled release technology that facilitate the development of an affordable universal influenza vaccine. PMID:24784572

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.

[Cost-effectiveness and cost-benefit analysis on strategy for preventing mother-to-child transmission of hepatitis B virus].

PubMed

Cai, Y L; Zhang, S X; Yang, P C; Lin, Y

2016-06-01

Through cost-benefit analysis (CBA), cost-effectiveness analysis (CEA) and quantitative optimization analysis to understand the economic benefit and outcomes of strategy regarding preventing mother-to-child transmission (PMTCT) on hepatitis B virus. Based on the principle of Hepatitis B immunization decision analytic-Markov model, strategies on PMTCT and universal vaccination were compared. Related parameters of Shenzhen were introduced to the model, a birth cohort was set up as the study population in 2013. The net present value (NPV), benefit-cost ratio (BCR), incremental cost-effectiveness ratio (ICER) were calculated and the differences between CBA and CEA were compared. A decision tree was built as the decision analysis model for hepatitis B immunization. Three kinds of Markov models were used to simulate the outcomes after the implementation of vaccination program. The PMTCT strategy of Shenzhen showed a net-gain as 38 097.51 Yuan/per person in 2013, with BCR as 14.37. The universal vaccination strategy showed a net-gain as 37 083.03 Yuan/per person, with BCR as 12.07. Data showed that the PMTCT strategy was better than the universal vaccination one and would end with gaining more economic benefit. When comparing with the universal vaccination program, the PMTCT strategy would save 85 100.00 Yuan more on QALY gains for every person. The PMTCT strategy seemed more cost-effective compared with the one under universal vaccination program. In the CBA and CEA hepatitis B immunization programs, the immunization coverage rate and costs of hepatitis B related diseases were the most important influencing factors. Outcomes of joint-changes of all the parameters in CEA showed that PMTCT strategy was a more cost-effective. The PMTCT strategy gained more economic benefit and effects on health. However, the cost of PMTCT strategy was more than the universal vaccination program, thus it is important to pay attention to the process of PMTCT strategy and the universal vaccination program. CBA seemed suitable for strategy optimization while CEA was better for strategy evaluation. Hopefully, programs as combination of the above said two methods would facilitate the process of economic evaluation.

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine.

PubMed

Rossi, Raffaella; Beernink, Peter T; Giuntini, Serena; Granoff, Dan M

2015-12-01

In 2013 and 2014, two U.S. universities had meningococcal serogroup B outbreaks (a total of 14 cases) caused by strains from two different clonal complexes. To control the outbreaks, students were immunized with a serogroup B meningococcal vaccine (Novartis) that was not yet licensed in the United States. The vaccine (referred to as MenB-4C) contains four components capable of eliciting bactericidal activity. Both outbreak strains had high expression levels of two of the vaccine antigens (subfamily B factor H binding protein [FHbp] and neisserial heparin binding antigen [NHba]); the university B outbreak strain also had moderate expression of a third antigen, NadA. We investigated the bactericidal activity of sera from mice immunized with FHbp, NHba, or NadA and sera from MenB-4C-immunized infant macaques and an adult human. The postimmunization bactericidal activity of the macaque or human serum against isolates from university B with FHbp identification (ID) 1 that exactly matched the vaccine FHbp sequence variant was 8- to 21-fold higher than that against isolates from university A with FHbp ID 276 (96% identity to the vaccine antigen). Based on the bactericidal activity of mouse antisera to FHbp, NadA, or NHba and macaque or human postimmunization serum that had been depleted of anti-FHbp antibody, the bactericidal activity against both outbreak strains largely or entirely resulted from antibodies to FHbp. Thus, despite the high level of strain expression of FHbp from a subfamily that matched the vaccine antigen, there can be large differences in anti-FHbp bactericidal activity induced by MenB-4C vaccination. Further, strains with moderate to high NadA and/or NHba expression can be resistant to anti-NadA or anti-NHba bactericidal activity elicited by MenB-4C vaccination. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Finding the sweet spots of inhibition: understanding the targets of a functional antibody against Plasmodium vivax Duffy binding protein

PubMed Central

Ntumngia, Francis B.; King, Christopher L.; Adams, John H.

2014-01-01

Plasmodium vivax Duffy binding protein region II (DBPII) is an essential ligand for reticulocyte invasion, thereby making this molecule an attractive vaccine candidate against asexual blood-stage P. vivax. Similar to other Plasmodium blood-stage vaccine candidates, strain-specific immunity due to DBPII allelic variation may complicate vaccine efficacy. Targeting immune responses to more conserved epitopes that are potential targets of strain-transcending neutralizing immunity is necessary to avoid induction of strain-specific responses to dominant variant epitopes. In this article, we focus on different approaches to optimize the design of DBP immunogenicity to target conserved epitopes, which is important for developing a broadly effective vaccine against P. vivax. PMID:23068913

A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth

NASA Astrophysics Data System (ADS)

Holmgren, Lars; Ambrosino, Elena; Birot, Olivier; Tullus, Carl; Veitonmäki, Niina; Levchenko, Tetyana; Carlson, Lena-Maria; Musiani, Piero; Iezzi, Manuela; Curcio, Claudia; Forni, Guido; Cavallo, Federica; Kiessling, Rolf

2006-06-01

Endogenous angiogenesis inhibitors have shown promise in preclinical trials, but clinical use has been hindered by low half-life in circulation and high production costs. Here, we describe a strategy that targets the angiostatin receptor angiomotin (Amot) by DNA vaccination. The vaccination procedure generated antibodies that detected Amot on the endothelial cell surface. Purified Ig bound to the endothelial cell membrane and inhibited endothelial cell migration. In vivo, DNA vaccination blocked angiogenesis in the matrigel plug assay and prevented growth of transplanted tumors for up to 150 days. We further demonstrate that a combination of DNA vaccines encoding Amot and the extracellular and transmembrane domains of the human EGF receptor 2 (Her-2)/neu oncogene inhibited breast cancer progression and impaired tumor vascularization in Her-2/neu transgenic mice. No toxicity or impairment of normal blood vessels could be detected. This work shows that DNA vaccination targeting Amot may be used to mimic the effect of angiostatin. cancer vaccines | neoplasia | neovascularization | breast cancer | angiostatin

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.

Intervene before leaving: clustered lot quality assurance sampling to monitor vaccination coverage at health district level before the end of a yellow fever and measles vaccination campaign in Sierra Leone in 2009

PubMed Central

2012-01-01

Background In November 2009, Sierra Leone conducted a preventive yellow fever (YF) vaccination campaign targeting individuals aged nine months and older in six health districts. The campaign was integrated with a measles follow-up campaign throughout the country targeting children aged 9–59 months. For both campaigns, the operational objective was to reach 95% of the target population. During the campaign, we used clustered lot quality assurance sampling (C-LQAS) to identify areas of low coverage to recommend timely mop-up actions. Methods We divided the country in 20 non-overlapping lots. Twelve lots were targeted by both vaccinations, while eight only by measles. In each lot, five clusters of ten eligible individuals were selected for each vaccine. The upper threshold (UT) was set at 90% and the lower threshold (LT) at 75%. A lot was rejected for low vaccination coverage if more than 7 unvaccinated individuals (not presenting vaccination card) were found. After the campaign, we plotted the C-LQAS results against the post-campaign coverage estimations to assess if early interventions were successful enough to increase coverage in the lots that were at the level of rejection before the end of the campaign. Results During the last two days of campaign, based on card-confirmed vaccination status, five lots out of 20 (25.0%) failed for having low measles vaccination coverage and three lots out of 12 (25.0%) for low YF coverage. In one district, estimated post-campaign vaccination coverage for both vaccines was still not significantly above the minimum acceptable level (LT = 75%) even after vaccination mop-up activities. Conclusion C-LQAS during the vaccination campaign was informative to identify areas requiring mop-up activities to reach the coverage target prior to leaving the region. The only district where mop-up activities seemed to be unsuccessful might have had logistical difficulties that should be further investigated and resolved. PMID:22676225

Asymptomatic Changes in Cardiac Function Can Occur in DCIS Patients Following Treatment with HER-2/neu Pulsed Dendritic Cell Vaccines

PubMed Central

Bahl, Susan; Roses, Robert; Sharma, Anupama; Koldovsky, Ursula; Xu, Shuwen; Weinstein, Susan; Nisenbaum, Harvey; Fox, Kevin; Pasha, Theresa; Zhang, Paul; Araujo, Louis; Carver, Joseph; Czerniecki, Brian J

2009-01-01

Background Targeting HER-2/neu with Trastuzumab has been associated with development of cardiac toxicity. Methods Twenty-seven patients with ductal carcinoma in situ (DCIS) of the breast completed an IRB approved clinical trial of a HER-2/neu targeted dendritic cell based vaccine. Four weekly vaccinations were administered prior to surgical resection. All subjects underwent pre- and post-vaccine cardiac monitoring by MUGA/ECHO scanning allowing for a comparison of cardiac function. Results In 3 of 27 vaccinated patients (11%) transient asymptomatic decrements in ejection fraction of greater than 15% were noted after vaccination. Notably, evidence of circulating anti-HER-2/neu antibody was found prior to vaccination in all three patients, but cardiac toxicity was not noted until induction of cellular mediated immune responses. Conclusions This is the first description of HER-2/neu targeted vaccination associated with an incidence of cardiac changes, and the induction of cellular immune responses combined with antibody may contribute to changes in cardiac function. PMID:19800453

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

PubMed

Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

2017-06-01

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

Birth control vaccine targeting leukemia inhibitory factor.

PubMed

Lemons, Angela R; Naz, Rajesh K

2012-02-01

The population explosion and unintended pregnancies resulting in elective abortions continue to impose major public health issues. This calls for a better method of contraception. Immunocontraception has been proposed as a valuable alternative that can fulfill most, if not all, of the properties of an ideal contraceptive. There are several targets that are being explored for contraceptive vaccine development. Leukemia inhibitory factor (LIF), a member of interleukin-6 family, is required for embryo development and successful blastocyst implantation in several mammalian species. The present study was conducted to examine if LIF can be a target for the development of a birth control vaccine. Three sequences from LIF and two sequences from LIF-receptor (LIF-R) that span the regions involved in ligand-receptor binding were delineated, and peptides were synthesized based upon these sequences. Antibodies raised against these five peptides reduced LIF bioactivity in an in vitro culture assay using BA/F3 mLIF-R-mpg130 cells. Vaccines were prepared by conjugating these peptides to various carrier proteins. Immunization of female mice with these peptide vaccines induced a long-lasting, circulating as well as local antibody response in various parts of the genital tract, and resulted in a significant (P ≤ 0.05) inhibition in fertility in all the three trials; the LIF-R peptide vaccines proved to be a better vaccine target. The data indicate that LIF/LIF-R is an excellent target for the development of a birth control vaccine. This is the first study, to our knowledge, that examined LIF/LIF-R as a target for immunocontraception. The findings of this study can be easily translated to humans since LIF/LIF-R is also important for implantation and pregnancy in women. Copyright © 2011 Wiley Periodicals, Inc.

First Universities Allied for Essential Medicines (UAEM) Neglected Diseases and Innovation Symposium.

PubMed

Musselwhite, Laura W; Maciag, Karolina; Lankowski, Alex; Gretes, Michael C; Wellems, Thomas E; Tavera, Gloria; Goulding, Rebecca E; Guillen, Ethan

2012-01-01

Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughput screening and medicinal chemistry research programs to identify lead compounds for small molecule drugs and novel drug targets. Furthermore, product development partnerships are emerging between academic institutions, non-profit entities, and biotechnology and pharmaceutical companies to create diagnostics, therapies, and vaccines for diseases of the poor. With not for profit mission statements, open access publishing standards, open source platforms for data sharing and collaboration, and a shift in focus to more translational research, universities and other public research institutions are well-placed to accelerate development of medical technologies, particularly for neglected tropical diseases.

To close the childhood immunization gap, we need a richer understanding of parents' decision-making.

PubMed

Corben, Paul; Leask, Julie

2016-12-01

Vaccination is widely acknowledged as one of the most successful public health interventions globally and in most high-income countries childhood vaccination coverage rates are moderately high. Yet in many instances, immunisation rates remain below aspirational targets and have shown only modest progress toward those targets in recent years, despite concerted efforts to improve uptake. In part, coverage rates reflect individual parents' vaccination attitudes and decisions and, because vaccination decision-making is complex and context-specific, it remains challenging at individual and community levels to assist parents to make positive decisions. Consequently, in the search for opportunities to improve immunisation coverage, there has been a renewed research focus on parents' decision-making. This review provides an overview of the literature surrounding parents' vaccination decision-making, offering suggestions for where efforts to increase vaccination coverage should be targeted and identifying areas for further research.

Measuring populations to improve vaccination coverage

NASA Astrophysics Data System (ADS)

Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

2016-10-01

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes.

Measuring populations to improve vaccination coverage

PubMed Central

Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

2016-01-01

In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes. PMID:27703191

The utility of prescreening for hepatitis A in military recruits prior to vaccination.

PubMed

Hirota, William K; Duncan, Marten B; Hirota, William K; Tsuchida, Amy

2002-11-01

The U.S. Army administers the hepatitis A virus (HAV) vaccination for prophylaxis against HAV infection. There is little comparative data as to whether prescreening for previous HAV infection before immunization is less costly than universal vaccination. We designed a study to determine the prevalence of previous HAV infection in U.S. Army recruits and then perform a cost analysis. The cost analysis compared selective vaccination versus universal vaccination. Basic demographic information, including age, gender, geographic origin, and ethnicity, were collected after which patients were tested for HAV antibodies. A total of 1,332 individuals was prospectively enrolled with 183 individuals (13.74%) having evidence of previous HAV infection. Minority recruits were found to have a higher prevalence than Caucasian recruits (p = 0.0451. The cost analysis demonstrates that vaccination without prescreening was the least costly of two vaccination strategies for this cohort. To achieve current vaccination goals, all U.S. military recruits should be vaccinated without evaluation for previous HAV immunity.

Predicted outcomes of vaccinating wildlife to reduce human risk of Lyme disease.

PubMed

Tsao, Kimberly; Fish, Durland; Galvani, Alison P

2012-07-01

Vaccination efforts for Lyme disease prevention in humans have focused on wildlife reservoirs to target the causative agent, Borrelia burgdorferi, for elimination in vector ticks. Multiple host species are involved in the transmission and maintenance of the bacterium, but not all host species can be vaccinated effectively. To evaluate vaccinating a subset of hosts in the context of host-tick interactions, we constructed and evaluated a dynamic model of B. burgdorferi transmission in mice. Our analyses indicate that on average, a mouse-targeted vaccine is expected to proportionally reduce infection prevalence among ticks by 56%. However, relative to mouse vaccination, human risk of exposure is dominated by the number of tick bites received per person, the proportion of tick blood meals taken from the highly reservoir-competent white-footed mouse relative to other hosts, and the average number of tick bites per mouse. Variation in these factors reduces the predictability of vaccination outcomes. Additionally, contributions of nonmouse hosts to pathogen maintenance preclude elimination of B. burgdorferi through mouse vaccination alone. Our findings indicate that to increase the impact of wildlife vaccination, reducing tick populations by acaricide application, in addition to targeting additional reservoir-competent host species, should be employed.

A longitudinal analysis of the effect of nonmedical exemption law and vaccine uptake on vaccine-targeted disease rates.

PubMed

Yang, Y Tony; Debold, Vicky

2014-02-01

We assessed how nonmedical exemption (NME) laws and annual uptake of vaccines required for school or daycare entry affect annual incidence rates for 5 vaccine-targeted diseases: pertussis, measles, mumps, Haemophilus influenzae type B, and hepatitis B. We employed longitudinal mixed-effects models to examine 2001-2008 vaccine-targeted disease data obtained from the National Notifiable Disease Surveillance System. Key explanatory variables were state-level vaccine-specific uptake rates from the National Immunization Survey and a state NME law restrictiveness level. NME law restrictiveness and vaccine uptake were not associated with disease incidence rate for hepatitis B, Haemophilus influenzae type B, measles, or mumps. Pertussis incidence rate, however, was negatively associated with NME law restrictiveness (b = -0.20; P = .03) and diphtheria-pertussis-tetanus vaccine uptake (b = -0.01; P = .05). State NME laws and vaccine uptake rates did not appear to influence lower-incidence diseases but may influence reported disease rates for higher-incidence diseases. If all states increased their NME law restrictiveness by 1 level and diphtheria-pertussis-tetanus uptake by 1%, national annual pertussis cases could decrease by 1.14% (171 cases) and 0.04% (5 cases), respectively.

The future for blood-stage vaccines against malaria.

PubMed

Richards, Jack S; Beeson, James G

2009-07-01

Malaria is a leading cause of mortality and morbidity globally, and effective vaccines are urgently needed. Malaria vaccine approaches can be broadly grouped as pre-erythrocytic, blood stage and transmission blocking. This review focuses on blood-stage vaccines, and considers the evidence supporting the development of blood-stage vaccines, the advantages and challenges of this approach, potential targets, human vaccine studies and future directions. There is a strong rationale for the development of vaccines based on antigens of blood-stage parasites. Symptomatic malaria is caused by blood-stage parasitemia and acquired immunity in humans largely targets blood-stage antigens. Several candidate vaccines have proved efficacious in animal models and at least one vaccine showed partial efficacy in a clinical trial. At present, all leading candidate blood-stage antigens are merozoite proteins, located on the merozoite surface or within the apical organelles. Major challenges and priorities include overcoming antigenic diversity, identification of protective epitopes, understanding the nature and targets of protective immune responses, and defining antigen combinations that give the greatest efficacy. Additionally, objective criteria and approaches are needed to prioritize the large number of candidate antigens, and strong candidates need to be tested in clinical trials as quickly as possible.

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

Ethnically diverse female university students' knowledge and attitudes toward human papillomavirus (HPV), HPV vaccination and cervical cancer.

PubMed

Wong, Li Ping; Sam, I-Ching

2010-01-01

Cervical HPV is the most common sexually transmitted disease among college-age women. This study aimed to assess knowledge and attitudes towards HPV infection, HPV vaccination and cervical cancer among female university students, to provide insight into development of HPV educational information. A cross-sectional survey using a convenience sample. A total of 1083 ethnically diverse female students attending a public university were approached and 650 were interviewed. Knowledge regarding HPV, HPV vaccination, cervical screening and cervical cancer risk factors was remarkably poor. Across the sample, the mean total knowledge score (14-item) was only 3.25 (S.D. +/-2.41; 95% CI 3.07-3.44). Only 10.3% had heard of the newly released HPV vaccine. Approximately 48% of participants indicated an intention to receive an HPV vaccine. Intention to receive an HPV vaccine was significantly associated with knowledge of HPV and genital warts (OR 1.53; 95% CI 1.25-1.88), and knowledge of cervical screening and cervical cancer risk factors (OR 1.21; 95% CI 1.11-1.33). Of those who refused HPV vaccination, 50.9% doubted the safety and efficacy of the new vaccine, and 41.5% perceived themselves as not at risk of HPV infection. The findings suggest that providing education about the etiology of cervical cancer and the HPV link is an essential component to enhance HPV vaccine uptake.

Inequalities in child immunization coverage in Ghana: evidence from a decomposition analysis.

PubMed

Asuman, Derek; Ackah, Charles Godfred; Enemark, Ulrika

2018-04-11

Childhood vaccination has been promoted as a global intervention aimed at improving child survival and health, through the reduction of vaccine preventable deaths. However, there exist significant inequalities in achieving universal coverage of child vaccination among and within countries. In this paper, we examine rural-urban inequalities in child immunizations in Ghana. Using data from the recent two waves of the Ghana Demographic and Health Survey, we examine the probability that a child between 12 and 59 months receives the required vaccinations and proceed to decompose the sources of inequalities in the probability of full immunization between rural and urban areas. We find significant child-specific, maternal and household characteristics on a child's immunization status. The results show that children in rural areas are more likely to complete the required vaccinations. The direction and sources of inequalities in child immunizations have changed between the two survey waves. We find a pro-urban advantage in 2008 arising from differences in observed characteristics whilst a pro-rural advantage emerges in 2014 dominated by the differences in coefficients. Health system development and campaign efforts have focused on rural areas. There is a need to also specifically target vulnerable children in urban areas, to maintain focus on women empowerment and pay attention to children from high socio-economic households in less favourable economic times.

Epidemiological Surveillance of Poliomyelitis During the Military and Political Conflict in the Central African Republic, 2013 and 2014.

PubMed

Farra, Alain; Gonofio, Ella C; Manirakiza, Alexandre; Mazitchi, Arthur; Mbaïlao, Raphaël; Manengu, Casimir; Gouandjika-Vasilache, Ionela

2017-01-01

Since December 2012, the Central African Republic (CAR) has been undergoing a severe military and political conflict. This situation has resulted in general insecurity and total disorganization of surveillance activities, including those for acute flaccid paralysis (AFP). In this study, we used laboratory data to evaluate surveillance of AFP in 2013 and 2014, the most critical period of the conflict. The laboratory data on AFP were analyzed retrospectively for the age, sex, vaccination status (oral poliovirus vaccines), and geographical origin of the samples. The χ 2 test was used, with P < .05 as the threshold for significance. Decreased activity of AFP surveillance of 57% was registered in 2013 and 36% in 2014 compared with previous years. Only 37.3% and 49.7% of children with AFP were vaccinated in 2013 and 2014, respectively, but no wild poliovirus or vaccine-derived poliovirus (VDPV) was isolated. Laboratory performance concerning the timeliness of cell culture and intratypic differentiation/VDPV results was only 65.5% and 66.7% of the target in 2013 but reached 95.5% and 100% in 2014. All personnel involved in the monitoring of AFP must be mobilized to improve vaccination coverage and surveillance activities in the CAR. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

A New Method for Estimating the Coverage of Mass Vaccination Campaigns Against Poliomyelitis From Surveillance Data.

PubMed

O'Reilly, K M; Cori, A; Durry, E; Wadood, M Z; Bosan, A; Aylward, R B; Grassly, N C

2015-12-01

Mass vaccination campaigns with the oral poliovirus vaccine targeting children aged <5 years are a critical component of the global poliomyelitis eradication effort. Monitoring the coverage of these campaigns is essential to allow corrective action, but current approaches are limited by their cross-sectional nature, nonrandom sampling, reporting biases, and accessibility issues. We describe a new Bayesian framework using data augmentation and Markov chain Monte Carlo methods to estimate variation in vaccination coverage from children's vaccination histories investigated during surveillance for acute flaccid paralysis. We tested the method using simulated data with at least 200 cases and were able to detect undervaccinated groups if they exceeded 10% of all children and temporal changes in coverage of ±10% with greater than 90% sensitivity. Application of the method to data from Pakistan for 2010-2011 identified undervaccinated groups within the Balochistan/Federally Administered Tribal Areas and Khyber Pakhtunkhwa regions, as well as temporal changes in coverage. The sizes of these groups are consistent with the multiple challenges faced by the program in these regions as a result of conflict and insecurity. Application of this new method to routinely collected data can be a useful tool for identifying poorly performing areas and assisting in eradication efforts. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Supplementary immunization activities to achieve measles elimination: experience of the European Region.

PubMed

Khetsuriani, Nino; Deshevoi, Sergei; Goel, Ajay; Spika, John; Martin, Rebecca; Emiroglu, Nedret

2011-07-01

Supplementary immunization activities (SIAs) using measles-containing vaccine (MCV) have had a substantial impact on reducing mortality associated with measles worldwide. To assess impact of SIAs on measles incidence in the World Health Organization European Region and their role at the final stages of measles elimination efforts in Europe, we reviewed information on SIAs, measles surveillance, and routine vaccination coverage during 2000-2009. During 2000-2009, >57 million persons received MCV through SIAs in 16 countries. The Region primarily focused on catch-up campaigns with wider target age groups than in other regions and subsequently relied on routine vaccination rather than periodic follow-up SIAs for the second MCV dose. In addition, the concept of SIAs has been expanded from short-term (<30 days) mass campaigns implemented in other regions to incorporate vaccination efforts over longer periods and outbreak response vaccination. In 2009, 14 of 16 countries that conducted SIAs reported no measles cases or <1 case per 1,000,000 population, reflecting the post-SIA decrease in incidence. SIAs have made a substantial contribution to the success of measles elimination efforts and will likely remain an important strategy for interrupting measles virus transmission in the European Region, although specific approaches will vary by country. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2011.

Enhanced immunogenicity of a tricomponent mannan tetanus toxoid conjugate vaccine targeted to dendritic cells via Dectin-1 by incorporating β-glucan.

PubMed

Lipinski, Tomasz; Fitieh, Amira; St Pierre, Joëlle; Ostergaard, Hanne L; Bundle, David R; Touret, Nicolas

2013-04-15

In a previous attempt to generate a protective vaccine against Candida albicans, a β-mannan tetanus toxoid conjugate showed poor immunogenicity in mice. To improve the specific activation toward the fungal pathogen, we aimed to target Dectin-1, a pattern-recognition receptor expressed on monocytes, macrophages, and dendritic cells. Laminarin, a β-glucan ligand of Dectin-1, was incorporated into the original β-mannan tetanus toxoid conjugate providing a tricomponent conjugate vaccine. A macrophage cell line expressing Dectin-1 was employed to show binding and activation of Dectin-1 signal transduction pathway by the β-glucan-containing vaccine. Ligand binding to Dectin-1 resulted in the following: 1) activation of Src family kinases and Syk revealed by their recruitment and phosphorylation in the vicinity of bound conjugate and 2) translocation of NF-κB to the nucleus. Treatment of immature bone marrow-derived dendritic cells (BMDCs) with tricomponent or control vaccine confirmed that the β-glucan-containing vaccine exerted its enhanced activity by virtue of dendritic cell targeting and uptake. Immature primary cells stimulated by the tricomponent vaccine, but not the β-mannan tetanus toxoid vaccine, showed activation of BMDCs. Moreover, treated BMDCs secreted increased levels of several cytokines, including TGF-β and IL-6, which are known activators of Th17 cells. Immunization of mice with the novel type of vaccine resulted in improved immune response manifested by high titers of Ab recognizing C. albicans β-mannan Ag. Vaccine containing laminarin also affected distribution of IgG subclasses, showing that vaccine targeting to Dectin-1 receptor can benefit from augmentation and immunomodulation of the immune response.

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

Rotavirus vaccines contribute towards universal health coverage in a mixed public-private healthcare system.

PubMed

Loganathan, Tharani; Jit, Mark; Hutubessy, Raymond; Ng, Chiu-Wan; Lee, Way-Seah; Verguet, Stéphane

2016-11-01

To evaluate rotavirus vaccination in Malaysia from the household's perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies the broader value of universal vaccination starting with non-health benefits such as financial risk protection and equity. These dimensions better enable decision-makers to evaluate policy on the public finance of health programmes. The incidence, health service utilisation and household expenditure related to rotavirus gastroenteritis according to national income quintiles were obtained from local data sources. Multiple birth cohorts were distributed into income quintiles and followed from birth over the first five years of life in a multicohort, static model. We found that the rich pay more out of pocket (OOP) than the poor, as the rich use more expensive private care. OOP payments among the poorest although small are high as a proportion of household income. Rotavirus vaccination results in substantial reduction in rotavirus episodes and expenditure and provides financial risk protection to all income groups. Poverty reduction benefits are concentrated amongst the poorest two income quintiles. We propose that universal vaccination complements health financing reforms in strengthening Universal Health Coverage (UHC). ECEA provides an important tool to understand the implications of vaccination for UHC, beyond traditional considerations of economic efficiency. © 2016 John Wiley & Sons Ltd.

How can the health belief model and self-determination theory predict both influenza vaccination and vaccination intention ? A longitudinal study among university students.

PubMed

Fall, Estelle; Izaute, Marie; Chakroun-Baggioni, Nadia

2018-06-01

Background and objective Seasonal influenza is frequent among students and often responsible for impaired academic performance and lower levels of general health. However, the vaccination rate in this population is very low. As the seasonal influenza vaccine is not compulsory in France, it is important to improve the vaccination uptake by identifying predictors of both intention and behaviour. This study investigated the effect of decisional balance, motivation and self-efficacy on vaccination acceptance using the Extended Health Belief Model (HBM) and Self-Determination Theory (SDT). Design and Main Outcome Measures University students were invited to fill in an online survey to answer questions about their influenza vaccination intention, and HBM and SDT constructs. A one-year longitudinal follow-up study investigated vaccination behaviour. Results Autonomous motivation and self-efficacy significantly influenced the intention to have the influenza vaccine, and vaccine behaviour at one-year follow-up. Intention predicted a significant proportion of variation (51%) in behaviour, and mediated the effect of these predictors on vaccination behaviour. Conclusion These results suggest that motivation concepts of the Self-Determination Theory can be adequately combined with the Health Belief Model to understand vaccination behaviour.

A significant and consistent reduction in rotavirus gastroenteritis hospitalization of children under 5 years of age, following the introduction of universal rotavirus immunization in Israel.

PubMed

Muhsen, Khitam; Rubenstein, Uri; Kassem, Eias; Goren, Sophy; Schachter, Yaakov; Kremer, Adi; Shulman, Lester M; Ephros, Moshe; Cohen, Dani

2015-01-01

Universal rotavirus vaccination with RotaTeq was introduced in Israel in December 2010. We examined hospitalization rates of children under 5 years of age due to all-cause and rotavirus gastroenteritis, both before and 3 years after universal introduction of the vaccination. An ongoing hospital-based surveillance network that was established in November 2007, accessed information regarding hospitalization of children due to gastroenteritis (n = 6205) in 3 hospitals in northern Israel, with an annual average of about 60,000 children under 5 years of age living in the catchment area of these hospitals. Stool samples were tested for rotavirus by immunochromatography. Compared to the period preceding implementation of the universal rotavirus vaccination (2008-2010), hospitalizations due to rotavirus gastroenteritis in children <5 years of age decreased significantly, by 55% (95% CI 43%-67%) during the period of universal vaccination (2011-2013), a decrease that was sustained throughout the 3 year period. This reduction was greater in children aged 0-23 months (60-61%) than in toddlers aged 24-59 months (36%). A 32% (95% CI 21%-45%) decrease in the incidence of all-cause gastroenteritis was also observed. During the period preceding universal vaccination, rotavirus diarrhea showed typical winter seasonality, with highest incidence in December. However, the winter peak was substantially blunted during the period of universal immunization. Surveillance of rotavirus gastroenteritis should continue to assess the long-term impact of such a program. Our findings are of relevance to high and middle-income countries considering the introduction of a universal rotavirus immunization program.

Assessing providers' vaccination behaviors during routine immunization in India.

PubMed

Cohen, Megan A; Gargano, Lisa M; Thacker, Naveen; Choudhury, Panna; Weiss, Paul S; Arora, Manisha; Orenstein, Walter A; Omer, Saad B; Hughes, James M

2015-08-01

Progress has been made toward improving routine immunization coverage in India, but universal coverage has not been achieved. Little is known about how providers' vaccination behaviors affect coverage rates. The purpose of this study was to identify provider behaviors that served as barriers to vaccination that could lead to missed opportunities to vaccinate. We conducted a study of health-care providers' vaccination behaviors during clinic visits for children <3 years of age. Information on provider behaviors was collected through parent report and direct observation. Compared with illness visits, parents were eight times more likely to report vaccination status was verified (p < 0.001) and three times more likely to report receiving counseling on immunization (p = 0.022) during vaccination visits. Training of all vaccination practitioners should focus on behaviors such as the necessity of verifying vaccination status regardless of visit type, stressing the importance of counseling parents on immunization and emphasizing what is a valid contraindication to vaccination. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Determination of knowledge levels, attitude and behaviors of female university students concerning cervical cancer, human papiloma virus and its vaccine.

PubMed

Yörük, Selda; Açıkgöz, Ayla; Ergör, Gül

2016-08-03

The purpose of the study is to investigate knowledge, attitudes and behaviours concerning cervical cancer, HPV and HPV vaccine of female students studying at a university in a health related department and explore variables affecting taking the vaccine. The research group consists of female students attending a health related department in Balıkesir University. The data of this cross-sectional research was collected via surveys. The average total knowledge score of the students concerning risks, symptoms and screening methods of cervical cancer and HPV vaccines was 14.15 ± 6.7. The HPV knowledge score of the students attending the faculty of medicine was higher compared to the students attending other departments and their HPV vaccine knowledge score was higher compared to the students attending nursing and paramedics students. The HPV vaccine knowledge score of the students attending the department of midwifery was significantly higher compared to other students. Only 0.9 % of the students took the vaccine. One third of the students who did not take the vaccine did not know that the vaccine was available in our country. In terms of the department that they attended, the students with a higher total knowledge score compared to the average (OR:1.5) and students with history of cancer in their families (OR:1.6) were more likely to consider taking the vaccine. Research group's knowledge on risk factors of cervical cancer, Pap smear test, symptoms and prevention ways of cancer, HPV and HPV vaccine was low.

Cost-effectiveness analysis of HPV vaccination: comparing the general population with socially vulnerable individuals.

PubMed

Han, Kyu-Tae; Kim, Sun Jung; Lee, Seo Yoon; Park, Eun-Cheol

2014-01-01

After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea.

Systematic review of the economic value of diarrheal vaccines

PubMed Central

Rheingans, Richard; Amaya, Mirna; Anderson, John D; Chakraborty, Poulomy; Atem, Jacob

2014-01-01

Diarrheal disease is a leading cause of child mortality in low-income settings and morbidity across a range of settings. A growing number of studies have addressed the economic value of new and emerging vaccines to reduce this threat. We conducted a systematic review to assess the economic value of diarrheal vaccines targeting a range of pathogens in different settings. The majority of studies focused on the economic value of rotavirus vaccines in different settings, with most of these concluding that vaccination would provide significant economic benefits across a range of vaccine prices. There is also evidence of the economic benefits of cholera vaccines in specific contexts. For other potential diarrheal vaccines data are limited and often hypothetical. Across all target pathogens and contexts, the evidence of economic value focuses the short-term health and economic gains. Additional information is needed on the broader social and long-term economic value of diarrhea vaccines. PMID:24861846

Finding the sweet spots of inhibition: understanding the targets of a functional antibody against Plasmodium vivax Duffy binding protein.

PubMed

Ntumngia, Francis B; King, Christopher L; Adams, John H

2012-11-01

Plasmodium vivax Duffy binding protein region II (DBPII) is an essential ligand for reticulocyte invasion, thereby making this molecule an attractive vaccine candidate against asexual blood-stage P. vivax. Similar to other Plasmodium blood-stage vaccine candidates, strain-specific immunity due to DBPII allelic variation may complicate vaccine efficacy. Targeting immune responses to more conserved epitopes that are potential targets of strain-transcending neutralising immunity is necessary to avoid induction of strain-specific responses to dominant variant epitopes. In this article, we focus on different approaches to optimise the design of DBP immunogenicity to target conserved epitopes, which is important for developing a broadly effective vaccine against P. vivax. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Impact of the national targeted Hepatitis A immunisation program in Australia: 2000-2014.

PubMed

Thompson, Craig; Dey, Aditi; Fearnley, Emily; Polkinghorne, Benjamin; Beard, Frank

2017-01-03

In November 2005, hepatitis A vaccine was funded under the Australian National Immunisation Program for Aboriginal and Torres Strait Islander (Indigenous) children aged 12-24months in the targeted jurisdictions of Queensland, South Australia, Western Australia and the Northern Territory. We reviewed the epidemiology of hepatitis A from 2000 to 2014 using data from the Australian National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and Australian Bureau of Statistics causes-of-death data. The impact of the national hepatitis A immunisation program was assessed by comparison of pre-vaccine (2000-2005) and post-vaccine time periods (2006-2014), by age group, Indigenous status and jurisdiction using incidence rate ratios (IRR) per 100,000 population and 95% confidence intervals (CI). The national pre-vaccine notification rate in Indigenous people was four times higher than the non-Indigenous rate, and declined from 8.41 per 100,000 (95% CI 5.03-11.79) pre-vaccine to 0.85 per 100,000 (95% CI 0.00-1.99) post-vaccine, becoming similar to the non-Indigenous rate. Notification and hospitalisation rates in Indigenous children aged <5years from targeted jurisdictions declined in the post-vaccine period when compared to the pre-vaccine period (notifications: IRR=0.07; 95% CI 0.04-0.13; hospitalisations: IRR=0.04; 95% CI 0.01-0.16). As did notification rates in Indigenous people aged 5-19 (IRR=0.08; 95% CI 0.05-0.13) and 20-49years (IRR=0.06; 95% CI 0.02-0.15) in targeted jurisdictions. For non-Indigenous people from targeted jurisdictions, notification rates decreased significantly in children aged <5years (IRR 0.47; 95% CI 0.31-0.71), and significantly more overall (IRR=0.43; 95% CI 0.39-0.47) compared to non-Indigenous people from non-targeted jurisdictions (IRR=0.60; 95% CI 0.56-0.64). The national hepatitis A immunisation program has had a significant impact in the targeted population with relatively modest vaccine coverage, with evidence suggestive of substantial herd protection effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes.

PubMed

Tőke, E R; Lőrincz, O; Csiszovszki, Z; Somogyi, E; Felföldi, G; Molnár, L; Szipőcs, R; Kolonics, A; Malissen, B; Lori, F; Trocio, J; Bakare, N; Horkay, F; Romani, N; Tripp, C H; Stoitzner, P; Lisziewicz, J

2014-06-01

There is no clinically available cancer immunotherapy that exploits Langerhans cells (LCs), the epidermal precursors of dendritic cells (DCs) that are the natural agent of antigen delivery. We developed a DNA formulation with a polymer and obtained synthetic 'pathogen-like' nanoparticles that preferentially targeted LCs in epidermal cultures. These nanoparticles applied topically under a patch-elicited robust immune responses in human subjects. To demonstrate the mechanism of action of this novel vaccination strategy in live animals, we assembled a high-resolution two-photon laser scanning-microscope. Nanoparticles applied on the native skin poorly penetrated and poorly induced LC motility. The combination of nanoparticle administration and skin treatment was essential both for efficient loading the vaccine into the epidermis and for potent activation of the LCs to migrate into the lymph nodes. LCs in the epidermis picked up nanoparticles and accumulated them in the nuclear region demonstrating an effective nuclear DNA delivery in vivo. Tissue distribution studies revealed that the majority of the DNA was targeted to the lymph nodes. Preclinical toxicity of the LC-targeting DNA vaccine was limited to mild and transient local erythema caused by the skin treatment. This novel, clinically proven LC-targeting DNA vaccine platform technology broadens the options on DC-targeting vaccines to generate therapeutic immunity against cancer.

Adjuvants and Inactivated Polio Vaccine: A Systematic Review

PubMed Central

Hawken, Jennifer; Troy, Stephanie B.

2012-01-01

Poliomyelitis is nearing universal eradication; in 2011, there were 650 cases reported globally. When wild polio is eradicated, global oral polio vaccine (OPV) cessation followed by universal use of inactivated polio vaccine (IPV) is believed to be the safest vaccination strategy as IPV does not mutate or run the risk of vaccine derived outbreaks that OPV does. However, IPV is significantly more expensive than OPV. One strategy to make IPV more affordable is to reduce the dose by adding adjuvants, compounds that augment the immune response to the vaccine. No adjuvants are currently utilized in stand-alone IPV; however, several have been explored over the past six decades. From aluminum, used in many licensed vaccines, to newer and more experimental adjuvants such as synthetic DNA, a diverse group of compounds has been assessed with varying strengths and weaknesses. This review summarizes the studies to date evaluating the efficacy and safety of adjuvants used with IPV. PMID:23041122

The influence of antigen targeting to sub-cellular compartments on the anti-allergic potential of a DNA vaccine.

PubMed

Weinberger, Esther E; Isakovic, Almedina; Scheiblhofer, Sandra; Ramsauer, Christina; Reiter, Katrin; Hauser-Kronberger, Cornelia; Thalhamer, Josef; Weiss, Richard

2013-12-09

Gene vaccines offer attractive rationales for prophylactic as well as therapeutic treatments of type I allergies. DNA and mRNA vaccines have been shown to prevent from allergic sensitization and to counterbalance established allergic immune reactions. Recent advances in gene vaccine manipulation offer additional opportunities for modulation of T helper cell profiles by specific targeting of cellular compartments. DNA vaccines encoding the major birch pollen allergen Bet v 1.0101 were equipped with different leader sequences to shuttle the antigen to lysosomes (LIMP-II), to trigger cellular secretion (hTPA), or to induce proteasomal degradation via forced ubiquitination (ubi). Mice were pre-vaccinated with these constructs and the protective efficacy was tested by subcutaneous Th2-promoting challenges, followed by allergen inhalation. IgG antibody subclass distribution and allergen-specific IgE as well as cytokine profiles from re-stimulated splenocytes and from BALFs were assessed. The cellular composition of BALFs, and lung resistance and compliance were determined. Immunization with all targeting variants protected from allergic sensitization, i.e. IgE induction, airway hyperresponsiveness, lung inflammation, and systemic and local Th2 cytokine expression. Surprisingly, protection did not clearly correlate with the induction of a systemic Th1 cytokine profile, but rather with proliferating CD4+ CD25+ FoxP3+ T regulatory cells in splenocyte cultures. Targeting the allergen to proteasomal or lysosomal degradation severely down-regulated antibody induction after vaccination, while T cell responses remained unaffected. Although secretion of antigen promoted the highest numbers of Th1 cells, this vaccine type was the least efficient in suppressing the establishment of an allergic immune response. This comparative analysis highlights the modulatory effect of antigen targeting on the resulting immune response, with a special emphasis on prophylactic anti-allergy DNA vaccination. Targeting the antigen to proteasomal or lysosomal degradation reduces the availability of native allergen, thereby rendering the vaccine hypoallergenic without compromising efficacy, an important feature for a therapeutic setting. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Applying Mathematical Tools to Accelerate Vaccine Development: Modeling Shigella Immune Dynamics

PubMed Central

Davis, Courtney L.; Wahid, Rezwanul; Toapanta, Franklin R.; Simon, Jakub K.

2013-01-01

We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella’s outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design. PMID:23589755

Applying mathematical tools to accelerate vaccine development: modeling Shigella immune dynamics.

PubMed

Davis, Courtney L; Wahid, Rezwanul; Toapanta, Franklin R; Simon, Jakub K; Sztein, Marcelo B; Levy, Doron

2013-01-01

We establish a mathematical framework for studying immune interactions with Shigella, a bacteria that kills over one million people worldwide every year. The long-term goal of this novel approach is to inform Shigella vaccine design by elucidating which immune components and bacterial targets are crucial for establishing Shigella immunity. Our delay differential equation model focuses on antibody and B cell responses directed against antigens like lipopolysaccharide in Shigella's outer membrane. We find that antibody-based vaccines targeting only surface antigens cannot elicit sufficient immunity for protection. Additional boosting prior to infection would require a four-orders-of-magnitude increase in antibodies to sufficiently prevent epithelial invasion. However, boosting anti-LPS B memory can confer protection, which suggests these cells may correlate with immunity. We see that IgA antibodies are slightly more effective per molecule than IgG, but more total IgA is required due to spatial functionality. An extension of the model reveals that targeting both LPS and epithelial entry proteins is a promising avenue to advance vaccine development. This paper underscores the importance of multifaceted immune targeting in creating an effective Shigella vaccine. It introduces mathematical models to the Shigella vaccine development effort and lays a foundation for joint theoretical/experimental/clinical approaches to Shigella vaccine design.

A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma

PubMed Central

Shibao, Shunsuke; Ueda, Ryo; Saito, Katsuya; Kikuchi, Ryogo; Nagashima, Hideaki; Kojima, Atsuhiro; Kagami, Hiroshi; Pareira, Eriel Sandika; Sasaki, Hikaru; Noji, Shinobu; Kawakami, Yutaka; Yoshida, Kazunari; Toda, Masahiro

2018-01-01

Object Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas. Methods Eight patients received intranodal vaccinations weekly at a dose of 2mg/kg bodyweight 8 times. T-lymphocyte responses against VEGF receptor (VEGFR) epitopes were assessed by enzyme linked immunosorbent spot assays. Results This treatment was well-tolerated in patients. The first four vaccines induced positive immune responses against at least one of the targeted VEGFR epitopes in the peripheral blood mononuclear cells in 87.5% of patients. The median overall survival time in all patients was 15.9 months. Two achieved progression-free status lasting at least 6 months. Two patients with recurrent GBM demonstrated stable disease. Plasma IL-8 level was negatively correlated with overall survival. Conclusion These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas. PMID:29765561

Harnessing the beneficial heterologous effects of vaccination

PubMed Central

Goodridge, Helen S.; Ahmed, S. Sohail; Curtis, Nigel; Kollmann, Tobias R.; Levy, Ofer; Netea, Mihai G.; Pollard, Andrew J.; van Crevel, Reinout; Wilson, Christopher B.

2016-01-01

Clinical evidence strongly suggests that certain live vaccines, in particular Bacille Calmette–Guérin (BCG) and measles vaccines, can reduce all-cause mortality, likely via protection against non-targeted pathogens in addition to the targeted pathogen. The underlying mechanisms are currently unknown. We discuss how heterologous lymphocyte activation and innate immune memory could promote protection beyond the intended target pathogen and consider how vaccinologists could leverage heterologous immunity to improve outcomes in vulnerable populations, in particular the very young and the elderly. PMID:27157064

Coverage and cost of a large oral cholera vaccination program in a high-risk cholera endemic urban population in Dhaka, Bangladesh.

PubMed

Khan, Iqbal Ansary; Saha, Amit; Chowdhury, Fahima; Khan, Ashraful Islam; Uddin, Md Jasim; Begum, Yasmin A; Riaz, Baizid Khoorshid; Islam, Sanjida; Ali, Mohammad; Luby, Stephen P; Clemens, John D; Cravioto, Alejandro; Qadri, Firdausi

2013-12-09

A feasibility study of an oral cholera vaccine was carried out to test strategies to reach high-risk populations in urban Mirpur, Dhaka, Bangladesh. The study was cluster randomized, with three arms: vaccine, vaccine plus safe water and hand washing practice, and no intervention. High risk people of age one year and above (except pregnant woman) from the two intervention arms received two doses of the oral cholera vaccine, Shanchol™. Vaccination was conducted between 17th February and 16th April 2011, with a minimum interval of fourteen days between two doses. Interpersonal communication preceded vaccination to raise awareness amongst the target population. The number of vaccine doses used, the population vaccinated, left-out, drop out, vaccine wastage and resources required were documented. Fixed outreach site vaccination strategy was adopted as the mode of vaccine delivery. Additionally, mobile vaccination sites and mop-up activities were carried out to reach the target communities. Of the 172,754 target population, 141,839 (82%) and 123,666 (72%) received complete first and second doses of the vaccine, respectively. Dropout rate from the first to the second dose was 13%. Two complete doses were received by 123,661 participants. Vaccine coverage in children was 81%. Coverage was significantly higher in females than in males (77% vs. 66%, P<0.001). Vaccine wastage for delivering the complete doses was 1.2%. The government provided cold-chain related support at no cost to the project. Costs for two doses of vaccine per-person were US$3.93, of which US$1.63 was spent on delivery. Cost for delivering a single dose was US$0.76. We observed no serious adverse events. Mass vaccination with oral cholera vaccine is feasible for reaching high risk endemic population through the existing national immunization delivery system employed by the government. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

The cost-effectiveness of two strategies for vaccinating US veterans with hepatitis C virus infection against hepatitis A and hepatitis B viruses.

PubMed

Jakiche, Rita; Borrego, Matthew E; Raisch, Dennis W; Gupchup, Gireesh V; Pai, Manjunath A; Jakiche, Antoine

2007-01-01

Although hepatitis A and B vaccinations are recommended for patients with chronic hepatitis C virus (HCV), the ideal vaccination strategy has not been determined. Our objective was to model the cost-effectiveness of two strategies for vaccinating patients with HCV infection against hepatitis A (HAV) and hepatitis B (HBV) viruses. The strategies evaluated were: universal vaccination with the combined HAV and HBV vaccine, and selective vaccination based on immunity determined by blood testing. A decision tree model was constructed to compare the cost-effectiveness of the two vaccination strategies from the New Mexico Veterans Affairs Health Care System (NMVAHCS) perspective. A retrospective review of all HCV patients (2517 subjects) at the NMVAHCS was performed to extract prevalence of immunity to HAV and HBV, and prevalence of decompensated liver disease. Literature review was performed to obtain other probabilities for the model. Only direct medical costs were considered; the effectiveness measure was the number of patients immune to both HAV and HBV. Sensitivity analyses were performed to test robustness of the results to changes in input variables. All costs were in 2004 US dollars. The selective strategy was less costly but less effective, with a cost-effectiveness ratio of 105 dollars per patient immune to HAV and HBV. The universal strategy was more effective but more expensive with a cost-effectiveness ratio of 112 dollars per patient immune to HAV and HBV. Compared with the selective strategy, universal strategy was associated with an incremental cost-effectiveness (ICE) ratio of 154 dollars per additional patient immune to HAV and HBV. The universal strategy would become more cost-effective if 1) the cost of combined vaccine was reduced to less than 30.75 dollars (9.7% reduction), 2) the cost of HBV vaccine increased to greater than 34.50 dollars (25% increase), 3) the cost of blood tests for immunity increased to more than 25.25 dollars (23% increase), or (4) the prevalence of anti-HBs decreased to less than 24%. The selective vaccination strategy for HAV and HBV in our sample of patients with HCV is more cost-effective. However, the universal strategy is more effective and its ICE is minimal, thus it may be worth the additional cost.

Vaccination Perceptions of College Students: With and without Vaccination Waiver.

PubMed

Jadhav, Emmanuel D; Winkler, Danielle L; Anderson, Billie S

2018-01-01

The resurgence of vaccine preventable diseases occurs more often among intentionally unvaccinated individuals, placing at direct risk young adults not caught up on vaccinations. The objectives of this study were to characterize the sociodemographic characteristics of young adults with and without vaccination waivers and identify their perceived benefits, barriers, and influencers of vaccination. Young adults ( n  = 964) from a Midwestern rural university responded to a survey (fall 2015-spring 2016) designed to identify their perception toward vaccination. Instrument consistency was measured using the Cronbach α-scores. The Chi-square test was used to test any sociodemographic differences and Mann-Whitney U -tests results for differences between exempt and non-exempt students. Analysis occurred in spring 2017. A little over one-third of young adults with a vaccination waiver were not up to date on their vaccinations, and think that vaccinations can cause autism. The biggest identifiable benefit was effective control against disease. The surveyed young adults ranked the out of pocket cost associated with vaccination as the most important barrier and safe and easy to use vaccines as the most important influencer of vaccination. Young adults who have had a vaccination waiver appear to not be up to date on their vaccinations. Vaccine administration programs, such as university campus clinics, would benefit from addressing perceptions unique to young adults with and without a vaccine waiver. This would subsequently better provide young adults a second shot for getting appropriately caught up on vaccinations.

Adenovirus-Based Vaccines against Rhesus Lymphocryptovirus EBNA-1 Induce Expansion of Specific CD8+ and CD4+ T Cells in Persistently Infected Rhesus Macaques

PubMed Central

Leskowitz, R.; Fogg, M. H.; Zhou, X. Y.; Kaur, A.; Silveira, E. L. V.; Villinger, F.; Lieberman, P. M.; Wang, F.

2014-01-01

ABSTRACT The impact of Epstein-Barr virus (EBV) on human health is substantial, but vaccines that prevent primary EBV infections or treat EBV-associated diseases are not yet available. The Epstein-Barr nuclear antigen 1 (EBNA-1) is an important target for vaccination because it is the only protein expressed in all EBV-associated malignancies. We have designed and tested two therapeutic EBV vaccines that target the rhesus (rh) lymphocryptovirus (LCV) EBNA-1 to determine if ongoing T cell responses during persistent rhLCV infection in rhesus macaques can be expanded upon vaccination. Vaccines were based on two serotypes of E1-deleted simian adenovirus and were administered in a prime-boost regimen. To further modulate the response, rhEBNA-1 was fused to herpes simplex virus glycoprotein D (HSV-gD), which acts to block an inhibitory signaling pathway during T cell activation. We found that vaccines expressing rhEBNA-1 with or without functional HSV-gD led to expansion of rhEBNA-1-specific CD8+ and CD4+ T cells in 33% and 83% of the vaccinated animals, respectively. Additional animals developed significant changes within T cell subsets without changes in total numbers. Vaccination did not increase T cell responses to rhBZLF-1, an immediate early lytic phase antigen of rhLCV, thus indicating that increases of rhEBNA-1-specific responses were a direct result of vaccination. Vaccine-induced rhEBNA-1-specific T cells were highly functional and produced various combinations of cytokines as well as the cytolytic molecule granzyme B. These results serve as an important proof of principle that functional EBNA-1-specific T cells can be expanded by vaccination. IMPORTANCE EBV is a common human pathogen that establishes a persistent infection through latency in B cells, where it occasionally reactivates. EBV infection is typically benign and is well controlled by the host adaptive immune system; however, it is considered carcinogenic due to its strong association with lymphoid and epithelial cell malignancies. Latent EBNA-1 is a promising target for a therapeutic vaccine, as it is the only antigen expressed in all EBV-associated malignancies. The goal was to determine if rhEBNA-1-specific T cells could be expanded upon vaccination of infected animals. Results were obtained with vaccines that target EBNA-1 of rhLCV, a virus closely related to EBV. We found that vaccination led to expansion of rhEBNA-1 immune cells that exhibited functions fit for controlling viral infection. This confirms that rhEBNA-1 is a suitable target for therapeutic vaccines. Future work should aim to generate more-robust T cell responses through modified vaccines. PMID:24522914

Cost Evaluation of a Government-Conducted Oral Cholera Vaccination Campaign-Haiti, 2013.

PubMed

Routh, Janell A; Sreenivasan, Nandini; Adhikari, Bishwa B; Andrecy, Lesly L; Bernateau, Margarette; Abimbola, Taiwo; Njau, Joseph; Jackson, Ernsley; Juin, Stanley; Francois, Jeannot; Tohme, Rania A; Meltzer, Martin I; Katz, Mark A; Mintz, Eric D

2017-10-01

The devastating 2010 cholera epidemic in Haiti prompted the government to introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We evaluated the direct costs associated with the government's first vaccine campaign implemented in August-September 2013. We analyzed data for major cost categories and assessed the efficiency of available campaign resources to vaccinate the target population. For a target population of 107,906 persons, campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and transport $0.35 per dose. Resources were greater than needed-our analyses suggested that approximately 2.5-6 times as many persons could have been vaccinated during this campaign without increasing the resources allocated for vaccine delivery and administration. These results can inform future OCV campaigns in Haiti.

Facts about Mumps for Adults

MedlinePlus

... containing vaccine or have other acceptable evidence of immunity to the disease. College and university students, healthcare ... MMR vaccine or have other acceptable evidence of immunity to ensure adequate protection. Vaccine safety The MMR ...

Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

PubMed Central

Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

2016-01-01

Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

An Interview with AIDS Vaccine Researcher Chris Parks

ERIC Educational Resources Information Center

Sullivan, Megan

2010-01-01

The search for an AIDS (acquired immune deficiency syndrome) vaccine is truly a global effort, with university laboratories, biotech firms, pharmaceutical companies, nonprofit research organizations, hospitals, and clinics all working together to develop an effective vaccine as quickly as possible. The International AIDS Vaccine Initiative (IAVI)…

Effectiveness of a web-based education program to improve vaccine storage conditions in primary care (Keep Cool): study protocol for a randomized controlled trial.

PubMed

Thielmann, Anika; Viehmann, Anja; Weltermann, Birgitta M

2015-07-14

Immunization programs are among the most effective public health strategies worldwide. Adequate vaccine storage is a prerequisite to assure the vaccines' effectiveness and safety. In a questionnaire survey among a random sample of German primary care physicians, we discovered vaccine storage deficits: 16% of physicians had experience with cold chain breaches either as an error or near error, 49 % did not keep a temperature log, and 21 % did not use a separate refrigerator for vaccine storage. In a recent feasibility study of 21 practice refrigerators, we showed that these were outside the target range 10.2% of the total time with some single refrigerators being outside the target range as much as 66.3% of the time. These cooling-chain deficits are consistent with the international medical literature, yet an effective, easy to disseminate, practice-centered intervention to improve storage conditions is lacking. This randomized intervention trial will be conducted in a random sample of primary care practices. Based on continuous temperature recordings over 7 days, all practices with readings outside the target range for vaccine storage (+2 °C to +8 °C) will be randomly allocated to a web-based education program or a waiting list control group. The practice physicians and their teams constitute the target population. Participants will be educated about best practices in vaccine storage and will receive a manual including storage checklists and templates for temperature documentation. In all practices, temperatures of the vaccine refrigerators will be monitored continuously using a data logger with a glycol probe as a surrogate for vaccine vial temperature. The effectiveness of the web-based education program will be determined after 6 months in terms of the proportion of refrigerators with vaccine vial temperatures within the target range (+2 °C to +8 °C) during 7-day temperature logging. Secondary outcome parameters include temperature monitoring, no critically low temperatures (≤ -0.5 °C), compliance with storage recommendations, knowledge of good vaccine storage conditions, and assignment of personnel as vaccine storage manager and backup. Keep Cool will develop and evaluate a web-based education program to improve vaccine storage conditions in primary care and thereby ensure immunization safety and effectiveness. DRKS00006561 (date of registration: 20 February 2015).

Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

PubMed

Valkenburg, Sophie A; Mallajosyula, V Vamsee Aditya; Li, Olive T W; Chin, Alex W H; Carnell, George; Temperton, Nigel; Varadarajan, Raghavan; Poon, Leo L M

2016-03-07

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies induced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.

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.

KISS1 can be used as a novel target for developing a DNA immunocastration vaccine in ram lambs.

PubMed

Han, Yanguo; Liu, Guiqiong; Jiang, Xunping; Ijaz, Nabeel; Tesema, Birhanu; Xie, Guangyue

2015-02-04

KISS1 gene-encoding kisspeptins are critical for the onset of puberty and control of adult fertility. This study investigated whether KISS1 can be used as a novel target for immunocastration. Human KISS1 was fused with the HBsAg-S gene for constructing an antibiotic-free recombinant plasmid pKS-asd that coded for 31.168 kDa target fusion protein. Six male Hu sheep lambs were divided into two equal groups, treatment and control. The vaccine (1mg/ram lamb) prepared in saline solution was injected into lambs at weeks 0, 3 and 6 of the experiment, respectively. Vaccine efficacy was evaluated in terms of KISS1-specific IgG antibody response, serum testosterone levels, scrotal circumference, testicular weight, length and breadth, extent of testicular tissue damage, and sexual behaviour changes. The specific anti-KISS1 antibody titre in vaccinated animals was significantly higher than that in controls (p<0.05). In addition, vaccinated animals showed lower serum testosterone level, testicular weight and length and smaller scrotal circumference than those in controls (p<0.05). Spermatogenesis of seminiferous tubules in vaccinated animals was suppressed; sexual behaviours in vaccinated animals were significantly lower (p<0.05) than those in controls. In conclusion, the immunization against KISS1 in this DNA vaccine induced a strong antibody response and resulted in the suppression of gonadal function and sexual behaviour in animals, demonstrating that KISS1 can be used as a novel target for developing a DNA immunocastration vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular sequence data of hepatitis B virus and genetic diversity after vaccination.

PubMed

van Ballegooijen, W Marijn; van Houdt, Robin; Bruisten, Sylvia M; Boot, Hein J; Coutinho, Roel A; Wallinga, Jacco

2009-12-15

The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.

Impact of hepatitis B vaccination on acute hepatitis B epidemiology in European Union/European Economic Area countries, 2006 to 2014

PubMed Central

Miglietta, Alessandro; Quinten, Chantal; Lopalco, Pier Luigi; Duffell, Erika

2018-01-01

Hepatitis B prevention in European Union/European Economic Area (EU/EEA) countries relies on vaccination programmes. We describe the epidemiology of acute hepatitis B virus (HBV) at country and EU/EEA level during 2006–2014. Using a multi-level mixed-effects Poisson regression model we assessed differences in the acute HBV infection notification rates between groups of countries that started universal HBV vaccination before/in vs after 1995; implemented or not a catch-up strategy; reached a vaccine coverage ≥ 95% vs < 95% and had a hepatitis B surface antigen prevalence ≥ 1% vs < 1%. Joinpoint regression analysis was used to assess trends by groups of countries, and additional Poisson regression models to evaluate the association between three-dose HBV vaccine coverage and acute HBV infection notification rates at country and EU/EEA level. The EU/EEA acute HBV infection notification rate decreased from 1.6 per 100,000 population in 2006 to 0.7 in 2014. No differences (p > 0.05) were found in the acute HBV infection notification rates between groups of countries, while as vaccine coverage increased, such rates decreased (p < 0.01). Countries with universal HBV vaccination before 1995, a catch-up strategy, and a vaccine coverage ≥ 95% had significant decreasing trends (p < 0.01). Ending HBV transmission in Europe by 2030 will require high vaccine coverage delivered through universal programmes, supported, where appropriate, by catch-up vaccination campaigns. PMID:29439751

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

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

Zhang, Han; Sonoda, Koh-Hei, E-mail: sonodak@med.kyushu-u.ac.jp; Hijioka, Kuniaki

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV,more » with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.« less

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization.

PubMed

Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8+ T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8+ T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

Predictors of Meningococcal Vaccination among University Students

ERIC Educational Resources Information Center

D'Heilly, Sarah; Ehlinger, Edward; Nichol, Kristin

2006-01-01

Invasive disease secondary to Neisseria meningitidis is a rare but devastating illness among university students. The Advisory Committee on Immunization Practices recommends educating college freshmen about meningococcal disease and vaccinating all college freshmen who live in residence halls. We conducted this survey to gain a better…

Physician Attitudes Regarding School-Located Vaccination Clinics

ERIC Educational Resources Information Center

Fiala, Steven C.; Cieslak, Paul R.; DeBess, Emilio E.; Young, Collette M.; Winthrop, Kevin L.; Stevenson, Ellen B.

2013-01-01

Background: School-located vaccination clinics offer an opportunity to target children for vaccination programs during communicable disease outbreaks. However, children in the United States are primarily vaccinated in the pediatrician's or family physician's office, and the concept of school-located vaccinations may be unfamiliar to some parents…

Parental acceptability of HPV vaccination for boys and girls aged 9-13 years in China - A population-based study.

PubMed

Wang, Zixin; Wang, Jingjing; Fang, Yuan; Gross, Danielle L; Wong, Martin C S; Wong, Eliza L Y; Lau, Joseph T F

2018-05-03

This study was to investigate parental acceptability of HPV vaccination for their sons and daughters aged 9-13 years under different cost scenarios, and factors associated with parental acceptability at market price. Participants were: (1) Chinese speaking parents aged 18-60 years with a Hong Kong ID card; (2) had a son or a daughter aged 9-13 years at the date of the survey; (3) the child had the right to abode in Hong Kong. Random telephone numbers were selected from up-to-date telephone directories of Hong Kong. A total of 300 eligible parents (boys' parents: 162; girls' parents: 138, response rate: 68.9% & 69%) provided verbal informed consent and completed the anonymous telephone interview during March to October 2016. Using parental acceptability of HPV vaccination at market price as the dependent variable, univariate and multiple logistic regression models were fitted. The prevalence of HPV vaccination was very low among boys and girls (0.6% vs. 2.2%, p = 0.242). Among those whose children had not taken up HPV vaccination, the prevalence of parental acceptability of HPV vaccination for the index son and daughter were: 14.9% and 27.4% (market price), and 51.6% and 63.0% (free vaccination). Adjusted for sociodemographic variables, attitudinal variables based on the Health Belief Model were associated with parental acceptability of HPV vaccination for their sons (perception that it was not worthy, perceived cue to action from mass media and perceived self-efficacy) and for their daughters (perceived susceptibility and perceived severity of HPV infection among females, perceived benefit of HPV vaccination and perceived self-efficacy). Coverage of HPV vaccination among children aged 9-13 years was very low. Instead of waiting for the free universal vaccination to become available, promotion of self-paid HPV vaccination targeting parents is urgently needed. Different strategies should be applied to boys' and girls' parents. Copyright © 2018 Elsevier Ltd. All rights reserved.

Advancing a vaccine to prevent human schistosomiasis.

PubMed

Merrifield, Maureen; Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

2016-06-03

Several candidate human schistosomiasis vaccines are in different stages of preclinical and clinical development. The major targets are Schistosoma haematobium (urogenitial schistosomiasis) and Schistosoma mansoni (intestinal schistosomiasis) that account for 99% of the world's 252 million cases, with 90% of these cases in Africa. Two recombinant S. mansoni vaccines - Sm-TSP-2 and Sm-14 are in Phase 1 trials, while Smp80 (calpain) is undergoing testing in non-human primates. Sh28GST, also known as Bilhvax is in advanced clinical development for S. haematobium infection. The possibility remains that some of these vaccines may cross-react to target both schistosome species. These vaccines were selected on the basis of their protective immunity in preclinical challenge models, through human immune-epidemiological studies or both. They are being advanced through a combination of academic research institutions, non-profit vaccine product development partnerships, biotechnology companies, and developing country vaccine manufacturers. In addition, new schistosome candidate vaccines are being identified through bioinformatics, OMICs approaches, and moderate throughput screening, although the full potential of reverse vaccinology for schistosomiasis has not yet been realized. The target product profiles of these vaccines vary but many focus on vaccinating children, in some cases following mass treatment with praziquantel, also known as vaccine-linked chemotherapy. Several regulatory pathways have been proposed, some of which rely on World Health Organization prequalification. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

[Conjugated vaccines].

PubMed

Fritzell, Bernard

2005-01-01

Encapsulated bacterial pathogens (e.g. Haemophilus influenzae type b [Hib], Neisseria meningitidis, or Streptococcus pneumoniae) target infants and young children who have lost any protective anti-capsular antibodies supplied maternally and whose immune systems are ineffective against T-independent antigens such as the polysaccharides of the capsule. The polysaccharide-protein conjugate vaccines overcome this limitation by converting the polysaccharide to a T-dependent antigen, which allows a vaccinated infant to mount a protective immune response. Where conjugated vaccines have been introduced into paediatric vaccination schedules, the incidence of invasive diseases caused by Hib, the group C meningococcus, or the pneumococcus has plummeted by at least 80%, a major public health success. Furthermore, surveillance has demonstrated that the conjugate vaccines provide 'herd protection' through their beneficial impact on nasopharyngeal colonisation among vaccinated children. Promising future approaches include enhancement of the number of capsular serogroups targeted by the meningococcal or pneumococcal conjugate vaccines.

R&D in Vaccines Targeting Neglected Diseases: An Exploratory Case Study Considering Funding for Preventive Tuberculosis Vaccine Development from 2007 to 2014

PubMed Central

Costa Barbosa Bessa, Theolis; Santos de Aragão, Erika; Medeiros Guimarães, Jane Mary

2017-01-01

Based on an exploratory case study regarding the types of institutions funding the research and development to obtain new tuberculosis vaccines, this article intends to provoke discussion regarding the provision of new vaccines targeting neglected disease. Although our findings and discussion are mainly relevant to the case presented here, some aspects are more generally applicable, especially regarding the dynamics of development in vaccines to prevent neglected diseases. Taking into account the dynamics of innovation currently seen at work in the vaccine sector, a highly concentrated market dominated by few multinational pharmaceutical companies, we feel that global PDP models can play an important role throughout the vaccine development cycle. In addition, the authors call attention to issues surrounding the coordination of actors and resources in the research, development, manufacturing, and distribution processes of vaccine products arising from PDP involvement. PMID:28133608

Augmenting Influenza-Specific T Cell Memory Generation with a Natural Killer T Cell-Dependent Glycolipid-Peptide Vaccine.

PubMed

Anderson, Regan J; Li, Jasmine; Kedzierski, Lukasz; Compton, Benjamin J; Hayman, Colin M; Osmond, Taryn L; Tang, Ching-Wen; Farrand, Kathryn J; Koay, Hui-Fern; Almeida, Catarina Filipa Dos Santos Sa E; Holz, Lauren R; Williams, Geoffrey M; Brimble, Margaret A; Wang, Zhongfang; Koutsakos, Marios; Kedzierska, Katherine; Godfrey, Dale I; Hermans, Ian F; Turner, Stephen J; Painter, Gavin F

2017-11-17

The development of a universal vaccine for influenza A virus (IAV) that does not require seasonal modification is a long-standing health goal, particularly in the context of the increasing threat of new global pandemics. Vaccines that specifically induce T cell responses are of considerable interest because they can target viral proteins that are more likely to be shared between different virus strains and subtypes and hence provide effective cross-reactive IAV immunity. From a practical perspective, such vaccines should induce T cell responses with long-lasting memory, while also being simple to manufacture and cost-effective. Here we describe the synthesis and evaluation of a vaccine platform based on solid phase peptide synthesis and bio-orthogonal conjugation methodologies. The chemical approach involves covalently attaching synthetic long peptides from a virus-associated protein to a powerful adjuvant molecule, α-galactosylceramide (α-GalCer). Strain-promoted azide-alkyne cycloaddition is used as a simple and efficient method for conjugation, and pseudoproline methodology is used to increase the efficiency of the peptide synthesis. α-GalCer is a glycolipid that stimulates NKT cells, a population of lymphoid-resident immune cells that can provide potent stimulatory signals to antigen-presenting cells engaged in driving proliferation and differentiation of peptide-specific T cells. When used in mice, the vaccine induced T cell responses that provided effective prophylactic protection against IAV infection, with the speed of viral clearance greater than that seen from previous viral exposure. These findings are significant because the vaccines are highly defined, quick to synthesize, and easily characterized and are therefore appropriate for large scale affordable manufacture.

Effectiveness of rotavirus vaccine in preventing severe gastroenteritis in young children according to socioeconomic status

PubMed Central

Gosselin, Virginie; Généreux, Mélissa; Gagneur, Arnaud; Petit, Geneviève

2016-01-01

ABSTRACT In 2011, the monovalent rotavirus vaccine was introduced into a universal immunization program in Quebec (Canada). This retrospective cohort study assessed vaccine effectiveness (VE) in preventing acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children <3 y living in the Quebec Eastern Townships region according to socioeconomic status (SES). Data were gathered from a tertiary hospital database paired with a regional immunization registry. Three cohorts of children were followed: (1) vaccinated children born in post-universal vaccination period (2011–2013, n = 5,033), (2) unvaccinated children born in post-universal vaccination period (n = 1,239), and (3) unvaccinated children born in pre-universal vaccination period (2008–2010, n = 6,436). In each cohort, AGE and RVGE hospitalizations were identified during equivalent follow-up periods to calculate VE globally and according to neighborhood-level SES. Using multivariable logistic regression, adjusted odds ratios (OR) were computed to obtain VE (1-OR). Adjusted VE of 2 doses was 62% (95% confidence interval [CI]: 37%–77%) and 94% (95%CI: 52%–99%) in preventing AGE and RVGE hospitalization, respectively. Stratified analyses according to SES showed that children living in neighborhoods with higher rates of low-income families had significantly lower VE against AGE hospitalizations compared to neighborhoods with lower rates of low-income families (30% vs. 78%, p = 0.027). Our results suggest that the rotavirus vaccine is highly effective in preventing severe gastroenteritis in young children, particularly among the most well-off. SES seems to influence rotavirus VE, even in a high-income country like Canada. Further studies are needed to determine factors related to lower rotavirus VE among socioeconomically disadvantaged groups. PMID:27367155

Rotavirus Infection in the Auckland Region After the Implementation of Universal Infant Rotavirus Vaccination: Impact on Hospitalizations and Laboratory Implications.

PubMed

McAuliffe, Gary N; Taylor, Susan L; Drinković, Dragana; Roberts, Sally A; Wilson, Elizabeth M; Best, Emma J

2018-01-01

In July 2014, New Zealand introduced universal infant vaccination with RotaTeq (Merk & Co.) administered as 3 doses at 6 weeks, 3 and 5 months of age. We sought to assess the impact of rotavirus vaccination on gastroenteritis (GE) hospitalizations in the greater Auckland region and analyze changes in rotavirus testing in the period around vaccine introduction. Hospitalizations, laboratory testing rates and methods were compared between the pre-vaccine period (2009-2013), post-vaccine period (January 2015 to December 2015) and year of vaccine introduction (2014). There was a 68% decline in rotavirus hospitalizations of children <5 years of age after vaccine introduction (from 258/100,000 to 83/100,000) and a 17% decline in all-cause gastroenteritis admissions (from 1815/100,000 to 1293/100,000). Reductions were also seen in pediatric groups too old to have received vaccine. Despite these changes, rotavirus testing rates in our region remained static in the year after vaccine introduction compared with the 2 prior years, and after vaccine introduction, we observed a high rate of false positives 19/58 (33%) in patients with reactive rotavirus tests. Rotavirus vaccine has had a significant early impact on gastroenteritis hospitalizations for children in the Auckland region. However, continued rotavirus testing at pre-vaccine rates risks generating false positive results. Laboratories and clinicians should consider reviewing their testing algorithms before vaccine introduction.

Epitope Mapping of Avian Influenza M2e Protein: Different Species Recognise Various Epitopes

PubMed Central

Hasan, Noor Haliza; Ignjatovic, Jagoda; Tarigan, Simson; Peaston, Anne; Hemmatzadeh, Farhid

2016-01-01

A common approach for developing diagnostic tests for influenza virus detection is the use of mouse or rabbit monoclonal and/or polyclonal antibodies against a target antigen of the virus. However, comparative mapping of the target antigen using antibodies from different animal sources has not been evaluated before. This is important because identification of antigenic determinants of the target antigen in different species plays a central role to ensure the efficiency of a diagnostic test, such as competitive ELISA or immunohistochemistry-based tests. Interest in the matrix 2 ectodomain (M2e) protein of avian influenza virus (AIV) as a candidate for a universal vaccine and also as a marker for detection of virus infection in vaccinated animals (DIVA) is the rationale for the selection of this protein for comparative mapping evaluation. This study aimed to map the epitopes of the M2e protein of avian influenza virus H5N1 using chicken, mouse and rabbit monoclonal or monospecific antibodies. Our findings revealed that rabbit antibodies (rAbs) recognized epitope 6EVETPTRN13 of the M2e, located at the N-terminal of the protein, while mouse (mAb) and chicken antibodies (cAbs) recognized epitope 10PTRNEWECK18, located at the centre region of the protein. The findings highlighted the difference between the M2e antigenic determinants recognized by different species that emphasized the importance of comparative mapping of antibody reactivity from different animals to the same antigen, especially in the case of multi-host infectious agents such as influenza. The findings are of importance for antigenic mapping, as well as diagnostic test and vaccine development. PMID:27362795

Designing oral vaccines targeting intestinal dendritic cells.

PubMed

Devriendt, Bert; De Geest, Bruno G; Cox, Eric

2011-04-01

Most pathogens colonize and invade the host at mucosal surfaces, such as the lung and the intestine. To combat intestinal pathogens the induction of local adaptive immune responses is required, which is mainly achieved through oral vaccination. However, most vaccines are ineffective when given orally owing to the hostile environment in the gastrointestinal tract. The encapsulation of antigens in biodegradable microparticulate delivery systems enhances their immunogenicity; however, the uptake of these delivery systems by intestinal immune cells is rather poor. Surface decoration of the particulates with targeting ligands could increase the uptake and mediate the selective targeting of the vaccine to intestinal antigen-presenting cells, including dendritic cells. In this review, current knowledge on dendritic cell subsets is discussed, along with progress in the development of selective antigen targeting to these cells, in addition to focusing on data obtained in mice and, where possible, the pig, as a non-rodent animal model for humans. Moreover, the potential use and benefits of Fcγ receptor-mediated targeting of antigen delivery systems are highlighted. In conclusion, dendritic cell targeting ligands grafted on antigen carrier systems should preferably bind to a conserved endocytotic receptor, facilitating the design of a multispecies vaccine platform, which could elicit robust protective immune responses against enteric pathogens.

[A cost-effectiveness analysis on universal infant rotavirus vaccination strategy in China].

PubMed

Sun, S L; Gao, Y Q; Yin, J; Zhuang, G H

2016-02-01

To evaluate the cost-effectiveness of current universal infant rotavirus vaccination strategy, in China. Through constructing decision tree-Markov model, we simulated rotavirus diarrhea associated cost and health outcome on those newborns in 2012 regarding different vaccination programs as: group with no vaccination, Rotavirus vaccination group and Rotateq vaccination group, respectively. We determined the optimal program, based on the comparison between incremental cost-effectiveness ratio (ICER) and China' s 2012 per capital gross domestic product (GDP). Compared with non-vaccination group, the Rotavirus vaccination and Rotateq vaccination groups had to pay 3 760 Yuan and 7 578 Yuan (both less than 2012 GDP per capital) to avert one disability adjusted life years (DALY) loss, respectively. RESULTS from sensitivity analysis indicated that both results were robust. Compared with Rotavirus vaccination program, the Rotateq vaccination program had to pay extra 81 068 Yuan (between 1 and 3 times GDP per capital) to avert one DALY loss. Data from the sensitivity analysis indicated that the result was not robust. From the perspective of health economics, both two-dose Rotarix vaccine and three-dose' s Rotateq vaccine programs were highly cost-effective, when compared to the non-vaccination program. It was appropriate to integrate rotavirus vaccine into the routine immunization program. Considering the large amount of extra cost that had to spend on Rotateq vaccination program, results from the sensitivity analysis showed that it was not robust. Rotateq vaccine required one more dose than the Rotarix vaccine, to be effective. However, it appeared more difficult to practice, suggesting that it was better to choose the Rotarix vaccine, at current stage.

Final analysis of a study assessing genital human papillomavirus genoprevalence in young Australian women, following eight years of a national vaccination program.

PubMed

Garland, Suzanne M; Cornall, Alyssa M; Brotherton, Julia M L; Wark, John D; Malloy, Michael J; Tabrizi, Sepehr N

2018-05-31

The VACCINE [Vaccine Against Cervical Cancer Impact and Effectiveness] study evaluated the prevalence of quadrivalent vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst young women of vaccine-eligible age. Between October 2011 - June 2015, women aged 18-25 years from Victoria, Australia, were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire and provided a self-collected vaginal swab for HPV DNA detection and genotyping (Linear Array HPV genotyping assay). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). Of 1223 who agreed to participate, 916 (74.9%) completed the survey and, for 1007 (82.3%) sexually-active participants, 744 (73.9%) returned the self-collected swab, of which 737 contained detectable DNA. 184/737 (25.0%) were positive for HPV. Vaccine-targeted HPV genotypes were detected in only 13 (1.7%) women: 11 HPV 16 (six vaccinated after sexual debut, five unvaccinated) and two HPV 6. Prevalence of any of HPV 31/33/45 collectively was 2.9%, varying significantly by vaccination status (fully 2.0%, unvaccinated 6.8%; p = 0.01). Vaccination rates among the sexually-active cohort were high, with 65.6%, 71.6% and 74.2% of participants having received three, at least two or at least one dose of vaccine, respectively. Of women self-reporting HPV vaccination, the NHVPR confirmed one or more doses were received in 90%. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. Surveillance five to eight years' post-initiation of a national HPV vaccination program demonstrated a consistent and very low prevalence of vaccine-related HPV genotypes and some evidence of cross protection against related types amongst vaccine-eligible women from Victoria, Australia. Copyright © 2018. Published by Elsevier Ltd.

Ethical and legal challenges of vaccines and vaccination: Reflections.

PubMed

Jesani, Amar; Johari, Veena

2017-01-01

Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.

Expansion of seasonal influenza vaccination in the Americas

PubMed Central

Ropero-Álvarez, Alba María; Kurtis, Hannah J; Danovaro-Holliday, M Carolina; Ruiz-Matus, Cuauhtémoc; Andrus, Jon K

2009-01-01

Background Seasonal influenza is a viral disease whose annual epidemics are estimated to cause three to five million cases of severe illness and 250,000 to 500,000 deaths worldwide. Vaccination is the main strategy for primary prevention. Methods To assess the status of influenza vaccination in the Americas, influenza vaccination data reported to the Pan American Health Organization (PAHO) through 2008 were analyzed. Results Thirty-five countries and territories administered influenza vaccine in their public health sector, compared to 13 countries in 2004. Targeted risk groups varied. Sixteen countries reported coverage among older adults, ranging from 21% to 100%; coverage data were not available for most countries and targeted populations. Some tropical countries used the Northern Hemisphere vaccine formulation and others used the Southern Hemisphere vaccine formulation. In 2008, approximately 166.3 million doses of seasonal influenza vaccine were purchased in the Americas; 30 of 35 countries procured their vaccine through PAHO's Revolving Fund. Conclusion Since 2004 there has been rapid uptake of seasonal influenza vaccine in the Americas. Challenges to fully implement influenza vaccination remain, including difficulties measuring coverage rates, variable vaccine uptake, and limited surveillance and effectiveness data to guide decisions regarding vaccine formulation and timing, especially in tropical countries. PMID:19778430

The Association between Influenza Vaccination and Other Preventative Health Behaviors in a Cohort of Pregnant Women

ERIC Educational Resources Information Center

Scheminske, Megan; Henninger, Michelle; Irving, Stephanie A.; Thompson, Mark; Williams, Jenny; Shifflett, Pat; Ball, Sarah W.; Avalos, Lyndsay Ammon; Naleway, Allison L.

2015-01-01

Objectives: Although pregnant women are a high-priority group for seasonal influenza vaccination, vaccination rates in this population remain below target levels. Previous studies have identified sociodemographic predictors of vaccine choice, but relationships between preconception heath behaviors and seasonal influenza vaccination are poorly…

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011–2012 season in Spain, among population targeted for vaccination

PubMed Central

2013-01-01

Background In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011–2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. Results The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0–69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions The 2011–2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season. PMID:24053661

Targeting dendritic cells--why bother?

PubMed

Kreutz, Martin; Tacken, Paul J; Figdor, Carl G

2013-04-11

Vaccination is among the most efficient forms of immunotherapy. Although sometimes inducing lifelong protective B-cell responses, T-cell-mediated immunity remains challenging. Targeting antigen to dendritic cells (DCs) is an extensively explored concept aimed at improving cellular immunity. The identification of various DC subsets with distinct functional characteristics now allows for the fine-tuning of targeting strategies. Although some of these DC subsets are regarded as superior for (cross-) priming of naive T cells, controversies still remain about which subset represents the best target for immunotherapy. Because targeting the antigen alone may not be sufficient to obtain effective T-cell responses, delivery systems have been developed to target multiple vaccine components to DCs. In this Perspective, we discuss the pros and cons of targeting DCs: if targeting is beneficial at all and which vaccine vehicles and immunization routes represent promising strategies to reach and activate DCs.

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.

Pricing of new vaccines

PubMed Central

McGlone, Sarah M

2010-01-01

New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; (4) Quantify the incremental value of the new vaccine's characteristics; (5) Determine vaccine positioning in the marketplace; (6) Estimate the vaccine price-demand curve; (7) Calculate vaccine costs (including those of manufacturing, distribution, and research and development); (8) Account for various legal, regulatory, third party payer and competitor factors; (9) Consider the overall product portfolio; (10) Set pricing objectives; (11) Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area. PMID:20861678

Pricing of new vaccines.

PubMed

Lee, Bruce Y; McGlone, Sarah M

2010-08-01

New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.

Review of DoD Malaria Research Programs,

DTIC Science & Technology

1992-05-01

the irraliated sporozoite vaccine. Work in the mouse model system and then extrapolate to human malarias. Study naturally acquired immune ...recombinant vaccines. Work simultaneously in the mouse model system and with human malarias. 3. Identify targets and mechanisms of protective immunity not...multivalent vaccines that attack these same targets. 3. Working again in the mouse model, non- human primate model, andI human systems we

Rules and tools that improved vaccines for children vaccine-ordering practices in Oregon: a 2010 pilot project.

PubMed

Hewett, Rafe; VanCuren, Anne; Trocio, Loralee; Beaudrault, Sara; Gund, Anona; Luther, Mimi; Groom, Holly

2013-01-01

This project's objective was to enhance efforts to improve vaccine-ordering efficiencies among targeted clinics using publicly purchased vaccines. Using an assessment of ordering behavior developed by the Centers for Disease Control and Prevention, we selected and trained immunization providers and assessed improvements in ordering behavior by comparing ordering patterns before and after the intervention. A total of 144 Vaccines for Children program providers in Oregon. We assessed 144 providers trained in the Economic Order Quantity process between January and November 2010. INTERVENTION (IF APPLICABLE): Providers were invited to participate in regional trainings. Trainings included assignment of ordering frequency and dissemination of tools to support adherence to the recommended ordering frequency. The percent increase in targeted clinics ordering according to recommended order frequency and the resulting decrease in orders placed, as an outcome of training and ordering tools. Only 35% of targeted providers were ordering according to the recommended ordering frequency before the project began. After completing training, utilizing ordering tools and ordering over a 7-month period, 78% of the targeted clinics were ordering according to the recommended frequency, a 120% increase in the number of clinics ordering with the recommended frequency. At baseline, targeted clinics placed 915 total vaccine orders over a 7-month period. After completing training and participating in the Economic Order Quantity process, only 645 orders were placed, a reduction of 30% . The initiative was successful in reducing the number of orders placed by Vaccines for Children providers in Oregon. A previous effort to reduce ordering, without the use of training or tools, did not achieve the same levels of provider compliance, suggesting that the addition of staff and development of tools were helpful in supporting behavior change and improving providers' ability to adhere to assigned order frequencies. Reducing order frequency results in more efficient vaccine ordering patterns and benefits vaccine distributors, Oregon Immunization Program staff, and provider staff.

Rabies Vaccination Targets for Stray Dog Populations

PubMed Central

Leung, Tiffany; Davis, Stephen A.

2017-01-01

The role of stray dogs in the persistence of domestic dog rabies, and whether removal of such dogs is beneficial, remains contentious issues for control programs seeking to eliminate rabies. While a community might reach the WHO vaccination target of 70% for dogs that can be handled, the stray or neighborhood dogs that are too wary of humans to be held are a more problematic population to vaccinate. Here, we present a method to estimate vaccination targets for stray dogs when the dog population is made up of stray, free-roaming, and confined dogs, where the latter two types are considered to have an identifiable owner. The control effort required for stray dogs is determined by the type-reproduction number, T1, the number of stray dogs infected by one rabid stray dog either directly or via any chain of infection involving owned dogs. Like the basic reproduction number R0 for single host populations, T1 determines the vaccination effort required to control the spread of disease when control is targeted at one host type, and there is a mix of host types. The application of T1 to rabies in mixed populations of stray and owned dogs is novel. We show that the outcome is sensitive to the vaccination coverage in the owned dog population, such that if vaccination rates of owned dogs were too low then no control effort targeting stray dogs is able to control or eliminate rabies. The required vaccination level also depends on the composition of the dog population, where a high proportion of either stray or free-roaming dogs implies unrealistically high vaccination levels are required to prevent rabies. We find that the required control effort is less sensitive to continuous culling that increases the death rate of stray dogs than to changes in the carrying capacity of the stray dog population. PMID:28451589

Immunization requirements of the top 200 universities: Implications for vaccine-hesitant families.

PubMed

Noesekabel, Allison; Fenick, Ada M

2017-06-22

The majority of pediatricians encounter vaccine hesitancy in their practices. As part of a broad discussion about vaccination, school requirements arise as a topic yet providers may lack information about the effects of immunization on university matriculation. We surveyed the top-ranked 200 universities regarding required immunizations, medical, religious, and philosophical exemptions, and noncompliance policies. We examined the legal requirements for involved jurisdictions. Of 129 responding universities (64%), 94% had ≥1 pre-matriculation immunization requirement (PIR), with a mean of 3.53 (95%CI 3.17-3.89) requirements. In unadjusted analyses, funding, region, jurisdictional requirements, undergraduate size, and tuition were significant predictors of the number of PIRs. In multivariate modeling, jurisdictional requirements outperformed all other university demographics, but excluding these, Northeast and South region and smaller undergraduate size persisted. The most common PIR was measles (93%). 67% of involved jurisdictions have laws mandating ≥1 university PIR, and 45% of universities surpassed their jurisdiction's law. With respect to medical, religious, and philosophical exemptions, 24%, 40%, and 60% of universities with PIRs had the highest hardship category, and 2%, 2%, and 46% disallowed these outright. Frequent responses to student noncompliance were: hold on classes (89%), additional registration fees (13%), and hold on housing (11%). Requirements for pre-matriculation immunizations in top universities are common and exemptions are difficult to obtain. Conversations between providers and vaccine-hesitant families may be enriched by discussion of these future effects of their decision on immunization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methods and Protocols for Developing Prion Vaccines.

PubMed

Marciniuk, Kristen; Taschuk, Ryan; Napper, Scott

2016-01-01

Prion diseases denote a distinct form of infectivity that is based in the misfolding of a self-protein (PrP(C)) into a pathological, infectious conformation (PrP(Sc)). Efforts to develop vaccines for prion diseases have been complicated by the potential dangers that are associated with induction of immune responses against a self-protein. As a consequence, there is considerable appeal for vaccines that specifically target the misfolded prion conformation. Such conformation-specific immunotherapy is made possible through the identification of vaccine targets (epitopes) that are exclusively presented as a consequence of misfolding. An immune response directed against these targets, termed disease-specific epitopes (DSEs), has the potential to spare the function of the native form of the protein while clearing, or neutralizing, the infectious isomer. Although identification of DSEs represents a critical first step in the induction of conformation-specific immune responses, substantial efforts are required to translate these targets into functional vaccines. Due to the poor immunogenicity that is inherent to self-proteins, and that is often associated with short peptides, substantial efforts are required to overcome tolerance-to-self and maximize the resultant immune response following DSE-based immunization. This often includes optimization of target sequences in terms of immunogenicity and development of effective formulation and delivery strategies for the associated peptides. Further, these vaccines must satisfy additional criteria from perspectives of specificity (PrP(C) vs. PrP(Sc)) and safety (antibody-induced template-driven misfolding of PrP(C)). The emphasis of this report is on the steps required to translate DSEs into prion vaccines and subsequent evaluation of the resulting immune responses.

Fusion Protein Vaccines Targeting Two Tumor Antigens Generate Synergistic Anti-Tumor Effects

PubMed Central

Cheng, Wen-Fang; Chang, Ming-Cheng; Sun, Wei-Zen; Jen, Yu-Wei; Liao, Chao-Wei; Chen, Yun-Yuan; Chen, Chi-An

2013-01-01

Introduction Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII)/E6 and PE(ΔIII)/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein. Materials and Methods In vivo antitumor effects including preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays including intracellular cytokine staining and ELISA for Ab responses were also performed. Results PE(ΔIII)/E6+PE(ΔIII)/E7 generated both stronger E6 and E7-specific immunity. Only 60% of the tumor protective effect was observed in the PE(ΔIII)/E6 group compared to 100% in the PE(ΔIII)/E7 and PE(ΔIII)/E6+PE(ΔIII)/E7 groups. Mice vaccinated with the PE(ΔIII)/E6+PE(ΔIII)/E7 fusion proteins had a smaller subcutaneous tumor size than those vaccinated with PE(ΔIII)/E6 or PE(ΔIII)/E7 fusion proteins alone. Conclusion Fusion protein vaccines targeting both E6 and E7 tumor antigens generated more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. This novel strategy of targeting two tumor antigens together can promote the development of cancer vaccines and immunotherapy in HPV-related malignancies. PMID:24058440

Are two doses of human papillomavirus vaccine sufficient for girls aged 15-18 years? Results from a cohort study in India.

PubMed

Bhatla, Neerja; Nene, Bhagwan M; Joshi, Smita; Esmy, Pulikottil O; Poli, Usha Rani Reddy; Joshi, Geeta; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Prabhu, Priya R; Basu, Partha; Muwonge, Richard; Hingmire, Sanjay; Sauvaget, Catherine; Lucas, Eric; Pawlita, Michael; Gheit, Tarik; Jayant, Kasturi; Malvi, Sylla G; Siddiqi, Maqsood; Michel, Angelika; Butt, Julia; Sankaran, Subha; Kannan, Thiraviam Pillai Rameshwari Ammal; Varghese, Rintu; Divate, Uma; Willhauck-Fleckenstein, Martina; Waterboer, Tim; Müller, Martin; Sehr, Peter; Kriplani, Alka; Mishra, Gauravi; Jadhav, Radhika; Thorat, Ranjit; Tommasino, Massimo; Pillai, M Radhakrishna; Sankaranarayanan, Rengaswamy

2018-06-01

Extending two-dose recommendations of HPV vaccine to girls between 15 and 18 years will reduce program cost and improve compliance. Immunogenicity and vaccine targeted HPV infection outcomes were compared between 1795 girls aged 15-18 years receiving two (1-180 days) and 1515 girls of same age receiving three (1-60-180 days) doses. Immunogenicity outcomes in 15-18 year old two-dose recipients were also compared with the 10-14 year old three-dose (N = 2833) and two-dose (N = 3184) recipients. The 15-18 year old two-dose recipients had non-inferior L1-binding antibody titres at seven months against vaccine-targeted HPV types compared to three-dose recipients at 15-18 years and three-dose recipients at 10-14 years of age. Neutralizing antibody titres at 18 months in 15-18 year old two-dose recipients were non-inferior to same age three-dose recipients for all except HPV 18. The titres were inferior to those in the 10-14 year old three-dose recipients for all targeted types. Frequency of incident infections from vaccine-targeted HPV types in the 15-18 year old two-dose recipients was similar to the three dose recipients. None of the girls receiving two or three doses had persistent infection from vaccine-targeted types. These findings support that two doses of HPV vaccine can be extended to girls aged 15-18 years. Copyright © 2018. Published by Elsevier B.V.

A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

PubMed Central

Schiller, John T.; Castellsagué, Xavier; Garland, Suzanne M.

2015-01-01

End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as high value public health interventions and justify their widespread implementation to prevent anogenital HPV infections and their associated neoplasia. This article forms part of a special supplement entitled “Opportunities for comprehensive control of HPV infections and related diseases” Vaccine Volume 30, Supplement X, 2012. PMID:23199956

Associated factors for recommending HBV vaccination to children among Georgian health care workers.

PubMed

Butsashvili, Maia; Kamkamidze, George; Topuridze, Marina; Morse, Dale; Triner, Wayne; DeHovitz, Jack; Nelson, Kenrad; McNutt, Louise-Anne

2012-12-20

Most cases of hepatitis B virus (HBV) infection and subsequent liver diseases can be prevented with universal newborn HBV vaccination. The attitudes of health care workers about HBV vaccination and their willingness to recommend vaccine have been shown to impact HBV vaccination coverage and the prevention of vertical transmission of HBV. The purpose of this study was to ascertain the factors associated with health care worker recommendations regarding newborn HBV vaccination. A cross-sectional study of prevalence and awareness of hepatitis B and hepatitis B vaccine was conducted among randomly selected physicians and nurses employed in seven hospitals in Georgia in 2006 and 2007. Self-administered questionnaires included a module on recommendations for HBV, HCV and HIV. Of the 1328 participants included in this analysis, 36% reported recommending against hepatitis B vaccination for children, including 33% of paediatricians. Among the 70.6% who provided a reason for not recommending HBV vaccine, the most common concern was an adverse vaccine event. Unvaccinated physicians and nurses were more likely to recommend against HBV vaccine (40.4% vs 11.4%, PR 3.54; 95% CI: 2.38, 5.29). Additionally, health care worker age was inversely correlated with recommendations for HBV vaccine with older workers less likely to recommend it. Vaccinating health care workers against HBV may provide a dual benefit by boosting occupational safety as well as strengthening universal coverage programs for newborns.

Assessing genital human papillomavirus genoprevalence in young Australian women following the introduction of a national vaccination program.

PubMed

Osborne, Sarah L; Tabrizi, Sepehr N; Brotherton, Julia M L; Cornall, Alyssa M; Wark, John D; Wrede, C David; Jayasinghe, Yasmin; Gertig, Dorota M; Pitts, Marian K; Garland, Suzanne M

2015-01-01

Following the implementation of Australia's National HPV Vaccination Program in April 2007, this study evaluated the prevalence of vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst vaccine-eligible young women. Between September 2011 and August 2013, women from Victoria, Australia aged 18-25 were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire, and sexually active women were asked to provide a self-collected vaginal swab for HPV deoxyribonucleic acid (DNA) detection and genotyping. Samples positive for HPV were genotyped using the Linear Array HPV genotyping test (Roche Diagnostics). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). Of 431 vaginal swabs, 24.8% were positive for HPV DNA. Vaccine-targeted HPV genotypes were detected in only seven (1.6%) samples; all HPV 16 (of the six HPV 16 positive vaccinated women, all had received the vaccine after sexual debut). There were no cases of HPV 6, 11 or 18 identified. HPV types 51, 59, 73, 84, and 89 were the most prevalent genotypes. Vaccination rates were high, with 77.3% of participants having received all three doses of the vaccine, and there was an 89.8% concordance between self-reported and registry-reported HPV vaccination status. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. Preliminary data from this study demonstrate a very low prevalence of vaccine-related HPV genotypes amongst vaccine-eligible women from Victoria, Australia. We were able to use Facebook to effectively reach and recruit young women to participate in the assessment of the impact of Australia's HPV vaccination program. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influenza Vaccine Uptake, Hand Hygiene Practices, and Perceived Barriers in Decision Making.

PubMed

Stedman-Smith, Maggie; Kingsbury, Diana M; Dubois, Cathy L Z; Grey, Scott F

2017-01-01

The annual costs of influenza are in the billions of dollars, with employers bearing substantial burdens. Yet, influenza vaccine uptake is sub-optimal. A random survey was administered to employees at a Midwestern public university using mixed quantitative and qualitative methods to identify the rate, characteristics, and barriers of self-reported flu vaccine uptake during March-April of 2012. The lowest uptake was among adults, ages 18 to 49 (29.8%), even though they are included in universal recommendations. Multiple regression analysis adjusted for demographic confounders showed an increase in self-identified protective hand hygiene behavior among those who reported influenza vaccine uptake compared with those who did not. Qualitative thematic analysis revealed contextual accounts of why vaccine uptake was declined including structural, perceptual, and knowledge barriers. Implementation and evaluation of novel multicomponent worksite vaccine interventions tailored to reach young and middle-aged employees including utilization of risk communication is needed to facilitate increased uptake.

Is it Right Time to Introduce Mumps Vaccine in Indias Universal Immunization Program?

PubMed

Vaidya, S R; Hamde, V S

2016-06-08

Measles, mumps and rubella are vaccine preventable diseases. However, morbidity and mortality due to these diseases remain largely unnoticed in India. Measles has received much attention; mumps and rubella still need to garner attention. According to the World Health Organization, near-elimination of mumps could be achieved by maintaining high vaccine coverage using a two-dose strategy. However, Government of India has not yet decided on mumps vaccine. In this review, we have reviewed sero-prevalence studies, vaccine studies, outbreak investigations, virus isolation and virus genotyping studies on mumps. Overall, mumps seems to be a significant public health problem in India, but does not garner attention due to the absence of a surveillance and documentation system. Thus, inclusion of mumps antigen in the Universal immunization program would have added advantages, the economic burden imposed by the cost of the vaccine offset by a reduction in disease burden.

Adjuvants and inactivated polio vaccine: a systematic review.

PubMed

Hawken, Jennifer; Troy, Stephanie B

2012-11-19

Poliomyelitis is nearing universal eradication; in 2011, there were 650 cases reported globally. When wild polio is eradicated, global oral polio vaccine (OPV) cessation followed by use of universal inactivated polio vaccine (IPV) is believed to be the safest vaccination strategy as IPV does not mutate or run the risk of vaccine derived outbreaks that OPV does. However, IPV is significantly more expensive than OPV. One strategy to make IPV more affordable is to reduce the dose by adding adjuvants, compounds that augment the immune response to the vaccine. No adjuvants are currently utilized in stand-alone IPV; however, several have been explored over the past six decades. From aluminum, used in many licensed vaccines, to newer and more experimental adjuvants such as synthetic DNA, a diverse group of compounds has been assessed with varying strengths and weaknesses. This review summarizes the studies to date evaluating the efficacy and safety of adjuvants used with IPV. Copyright © 2012 Elsevier Ltd. All rights reserved.

ONR Far East Scientific Bulletin. Volume 10, Number 3, July-September 1985,

DTIC Science & Technology

1985-09-01

to alpha and beta interferon. " Vaccines Using recombinant DNA technology, researchers at Osaka University have developed a vaccine against the Chicken ... Pox virus. Using recombinant DNA technology, researchers at Kyushu University have developed a vaccine against the Herpes simplex virus. " Drugs...Germany 9 Norway 8 Holland 7 U.K. 6 France 4 Denmark 4 Austria 4 U.S.S.R. 3 Australia 2 Singapore 2 Spain 2 Poland I Egypt I Israel I Mexico I 20

Hepatitis B vaccination coverage and risk factors associated with incomplete vaccination of children born to hepatitis B surface antigen-positive mothers, Denmark, 2006 to 2010.

PubMed

Kunoee, Asja; Nielsen, Jens; Cowan, Susan

2016-01-01

In Denmark, universal screening of pregnant women for hepatitis B has been in place since November 2005, with the first two years as a trial period with enhanced surveillance. It is unknown what the change to universal screening without enhanced surveillance has meant for vaccination coverage among children born to hepatitis B surface antigen (HBsAg)-positive mothers and what risk factors exist for incomplete vaccination. This retrospective cohort study included 699 children of mothers positive for HBsAg. Information on vaccination and risk factors was collected from central registers. In total, 93% (651/699) of the children were vaccinated within 48 hours of birth, with considerable variation between birthplaces. Only 64% (306/475) of the children had received all four vaccinations through their general practitioner (GP) at the age of two years, and 10% (47/475) of the children had received no hepatitis B vaccinations at all. Enhanced surveillance was correlated positively with coverage of birth vaccination but not with coverage at the GP. No or few prenatal examinations were a risk factor for incomplete vaccination at the GP. Maternity wards and GPs are encouraged to revise their vaccination procedures and routines for pregnant women, mothers with chronic HBV infection and their children.

Blood-stage malaria vaccines: post-genome strategies for the identification of novel vaccine candidates.

PubMed

Ntege, Edward H; Takashima, Eizo; Morita, Masayuki; Nagaoka, Hikaru; Ishino, Tomoko; Tsuboi, Takafumi

2017-08-01

An efficacious malaria vaccine is necessary to advance the current control measures towards malaria elimination. To-date, only RTS,S/AS01, a leading pre-erythrocytic stage vaccine completed phase 3 trials, but with an efficacy of 28-36% in children, and 18-26% in infants, that waned over time. Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy. Therefore, novel blood-stage vaccine candidate discovery efforts are critical, albeit with several challenges including, high polymorphisms in vaccine antigens, poor understanding of targets of naturally protective immunity, and difficulties in the expression of high AT-rich plasmodial proteins. Areas covered: PubMed ( www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future prospects of malaria vaccine research and development. We focused on post-genome vaccine candidate discovery, malaria vaccine development, sequence diversity, pre-clinical and clinical trials. Expert commentary: Post-genome high-throughput technologies using wheat germ cell-free protein synthesis technology and immuno-profiling with sera from malaria patients with clearly defined outcomes are highlighted to overcome current challenges of malaria vaccine candidate discovery.

Targeting of non-dominant antigens as a vaccine strategy to broaden T-cell responses during chronic viral infection.

PubMed

Holst, Peter J; Jensen, Benjamin A H; Ragonnaud, Emeline; Thomsen, Allan R; Christensen, Jan P

2015-01-01

In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes facilitates potent virus-induced T-cell responses against immunodominant epitopes during subsequent challenge with highly invasive virus. In contrast, when an immunodominant epitope was included in the vaccine, the T-cell response associated with viral challenge remained focussed on that epitope. Early after challenge with live virus, the CD8+ T cells specific for vaccine-encoded epitopes, displayed a phenotype typically associated with prolonged/persistent antigenic stimulation marked by high levels of KLRG-1, as compared to T cells reacting to epitopes not included in the vaccine. Notably, this association was lost over time in T cells specific for the dominant T cell epitopes, and these cells were fully capable of expanding in response to a new viral challenge. Overall, our data suggests a potential for broadening of the antiviral CD8+ T-cell response by selecting non-dominant antigens to be targeted by vaccination. In addition, our findings suggest that prior adenoviral vaccination is not likely to negatively impact the long-term and protective immune response induced and maintained by a vaccine-attenuated chronic viral infection.

Post-licensure deployment of oral cholera vaccines: a systematic review

PubMed Central

Martin, Stephen; Lopez, Anna Lena; Bellos, Anna; Ali, Mohammad; Alberti, Kathryn; Anh, Dang Duc; Costa, Alejandro; Grais, Rebecca F; Legros, Dominique; Luquero, Francisco J; Ghai, Megan B; Perea, William; Sack, David A

2014-01-01

Abstract Objective To describe and analyse the characteristics of oral cholera vaccination campaigns; including location, target population, logistics, vaccine coverage and delivery costs. Methods We searched PubMed, the World Health Organization (WHO) website and the Cochrane database with no date or language restrictions. We contacted public health personnel, experts in the field and in ministries of health and did targeted web searches. Findings A total of 33 documents were included in the analysis. One country, Viet Nam, incorporates oral cholera vaccination into its public health programme and has administered approximately 10.9 million vaccine doses between 1997 and 2012. In addition, over 3 million doses of the two WHO pre-qualified oral cholera vaccines have been administered in more than 16 campaigns around the world between 1997 and 2014. These campaigns have either been pre-emptive or reactive and have taken place under diverse conditions, such as in refugee camps or natural disasters. Estimated two-dose coverage ranged from 46 to 88% of the target population. Approximate delivery cost per fully immunized person ranged from 0.11–3.99 United States dollars. Conclusion Experience with oral cholera vaccination campaigns continues to increase. Public health officials may draw on this experience and conduct oral cholera vaccination campaigns more frequently. PMID:25552772

Protecting the next generation: what is the role of the duration of human papillomavirus vaccine-related immunity?

PubMed

Günther, Oliver P; Ogilvie, Gina; Naus, Monika; Young, Eric; Patrick, David M; Dobson, Simon; Duval, Bernard; Noël, Pierre-André; Marra, Fawziah; Miller, Dianne; Brunham, Robert C; Pourbohloul, Babak

2008-06-15

There is strong evidence that human papillomavirus (HPV) is necessary for the development of cervical cancer. A prophylactic HPV vaccine with high reported efficacy was approved in North America in 2006. A mathematical model of HPV transmission dynamics was used to simulate different scenarios of natural disease outcomes and intervention strategies. A sensitivity analysis was performed to compensate for uncertainties surrounding key epidemiological parameters. The expected impact that HPV vaccines have on cervical cancer incidence and HPV prevalence in the province of British Columbia in Canada revealed that, for lifelong vaccine-related protection, an immunization routine targeting younger females (grade 6), combined with a 3-year program for adolescent females (grade 9), is the most effective strategy. If vaccine-related protection continues for <10 years, then the targeting of adolescent females would be more beneficial than the targeting of younger females. The incremental benefit if boys, as well as girls, are vaccinated is small. Optimization of the design of immunization strategies for treatment of HPV depends substantially on the duration of vaccine-induced immunity. Given the uncertainty in estimating this duration, it may be prudent to assume a value close to the lower limit reported and adjust the program when more-accurate information for the length of vaccine-induced immunity becomes available.

Knowledge, Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands.

PubMed

Burnett, Eleanor; Dalipanda, Tenneth; Ogaoga, Divi; Gaiofa, Jenny; Jilini, Gregory; Halpin, Alison; Dietz, Vance; Date, Kashmira; Mintz, Eric; Hyde, Terri; Wannemuehler, Kathleen; Yen, Catherine

2016-08-01

In response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1-15 years in selected communities in Choiseul and Western Provinces. We conducted a post-vaccination campaign, household-level survey about knowledge, attitudes, and practices regarding diarrhea and cholera in areas targeted and not targeted for cholera vaccination. Respondents in vaccinated areas were more likely to have received cholera education in the previous 6 months (33% v. 9%; p = 0.04), to know signs and symptoms (64% vs. 22%; p = 0.02) and treatment (96% vs. 50%; p = 0.02) of cholera, and to be aware of cholera vaccine (48% vs. 14%; p = 0.02). There were no differences in water, sanitation, and hygiene practices. This pre-emptive OCV campaign in a cholera-naïve community provided a unique opportunity to assess household-level knowledge, attitudes, and practices regarding diarrhea, cholera, and water, sanitation, and hygiene (WASH). Our findings suggest that education provided during the vaccination campaign may have reinforced earlier mass messaging about cholera and diarrheal disease in vaccinated communities.

Predicting influenza vaccination uptake among health care workers: what are the key motivators?

PubMed

Corace, Kimberly; Prematunge, Chatura; McCarthy, Anne; Nair, Rama C; Roth, Virginia; Hayes, Thomas; Suh, Kathryn N; Balfour, Louise; Garber, Gary

2013-08-01

Health care worker (HCW) vaccination was critical to protecting HCW during the H1N1 pandemic. However, vaccine uptake rates fell below recommended targets. This study examined motivators and barriers influencing HCW pH1N1 vaccination to identify modifiable factors that can improve influenza vaccine uptake. A cross-sectional survey was conducted at a large Canadian tertiary care hospital. HCW (N = 3,275) completed measures of demographics, vaccination history, influenza risk factors, and attitudes toward pH1N1 vaccination. Self-reported vaccination was verified with staff vaccination records. Of the total sample, 2,862 (87.4%) HCW received the pH1N1 vaccine. Multiple logistic regression analyses were used to predict HCW vaccination. HCW attitudes toward vaccination significantly predicted vaccination, even after adjusting for demographics, vaccine history, and influenza risk factors. This model correctly predicted 95% (confidence interval [CI]: 0.93-0.96) of HCW vaccination. Key modifiable factors driving HCW vaccination include (1) desire to protect family members and patients, (2) belief that vaccination is important even if one is healthy, (3) confidence in vaccine safety, and (4) supervisor and physician encouragement. This research identified fundamental reasons why HCW get vaccinated and provides direction for future influenza vaccination programs. To enhance vaccine uptake, it is important to target HCW attitudes in influenza vaccine campaigns and create a culture of vaccine promotion in the workplace, including strong messaging from supervisors and physicians. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Alteration of the Tumor Stroma Using a Consensus DNA Vaccine Targeting Fibroblast Activation Protein (FAP) Synergizes with Antitumor Vaccine Therapy in Mice.

PubMed

Duperret, Elizabeth K; Trautz, Aspen; Ammons, Dylan; Perales-Puchalt, Alfredo; Wise, Megan C; Yan, Jian; Reed, Charles; Weiner, David B

2018-03-01

Purpose: Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts and is an interesting target for cancer immune therapy, with prior studies indicating a potential to affect the tumor stroma. Our aim was to extend this earlier work through the development of a novel FAP immunogen with improved capacity to break tolerance for use in combination with tumor antigen vaccines. Experimental Design: We used a synthetic consensus (SynCon) sequence approach to provide MHC class II help to support breaking of tolerance. We evaluated immune responses and antitumor activity of this novel FAP vaccine in preclinical studies, and correlated these findings to patient data. Results: This SynCon FAP DNA vaccine was capable of breaking tolerance and inducing both CD8 + and CD4 + immune responses. In genetically diverse, outbred mice, the SynCon FAP DNA vaccine was superior at breaking tolerance compared with a native mouse FAP immunogen. In several tumor models, the SynCon FAP DNA vaccine synergized with other tumor antigen-specific DNA vaccines to enhance antitumor immunity. Evaluation of the tumor microenvironment showed increased CD8 + T-cell infiltration and a decreased macrophage infiltration driven by FAP immunization. We extended this to patient data from The Cancer Genome Atlas, where we find high FAP expression correlates with high macrophage and low CD8 + T-cell infiltration. Conclusions: These results suggest that immune therapy targeting tumor antigens in combination with a microconsensus FAP vaccine provides two-fisted punch-inducing responses that target both the tumor microenvironment and tumor cells directly. Clin Cancer Res; 24(5); 1190-201. ©2018 AACR . ©2018 American Association for Cancer Research.

Periodic updating of avian influenza vaccines is necessary to maintain effectiveness in the field

USDA-ARS?s Scientific Manuscript database

The impact of avian influenza on poultry production is undeniable. Field outbreaks of H5N1 HPAI have occurred in vaccinated flocks from both failure of the vaccines (i.e. vaccine efficacy) and failure in administration or immune response of the target species (i.e. vaccination effectiveness). Antige...

European Society for Paediatric Infectious Diseases consensus recommendations for rotavirus vaccination in Europe: update 2014.

PubMed

Vesikari, Timo; Van Damme, Pierre; Giaquinto, Carlo; Dagan, Ron; Guarino, Alfredo; Szajewska, Hania; Usonis, Vytautas

2015-06-01

The first evidence-based recommendations for rotavirus (RV) vaccination in Europe were prepared at the time of licensure of 2 live oral RV vaccines (Rotarix, GlaxoSmithKline Biologicals, and RotaTeq, Sanofi Pasteur MSD) in 2006 and published in 2008. Since then several countries in Europe and more globally have adopted universal RV vaccination of all healthy infants as part of their national immunization programs (NIPs). The experience from these NIPs has produced a wealth of post-introduction effectiveness data that, together with the evidence from prelicensure efficacy trials presented in the 2008 Recommendations, support the case of RV vaccination in Europe. The prelicensure safety trials of Rotarix and RotaTeq, each in populations of more than 60,000 infants, did not reveal risk of intussusception (IS), but postvaccination surveillance in several countries, particularly Australia and Mexico, has established that the risk of IS for both vaccines after the first dose might be between 1:50,000 and 1:80,000. Although it may be argued that the risk is acceptable vis-à-vis the great benefits of RV vaccination, this argument alone may not suffice, and every effort should be made to reduce the risk of IS. Considerable evidence, including postvaccination surveillance data from Germany, suggests that the risk of IS can be reduced by early administration of the first dose of oral RV vaccine. The previous European Society for Paediatric Infectious Diseases/European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommendations held that the first dose of oral RV vaccine should be given between 6 and 12 weeks of age; this recommendation is sustained but with an emphasis toward the lower range of the recommended age, that is, preferably between 6 and 8 weeks of age. At the time of the earlier recommendations, experience of RV vaccination in premature infants and other special target groups was limited. It is now recommended with greater confidence than before that prematurely born infants should be vaccinated according to their calendar age as recommended for full-term infants. It is now strongly recommended that all HIV-infected or HIV-exposed infants should be vaccinated with oral RV vaccine. Although specific information on many immunodeficiencies is lacking, infants with known severe combined immunodeficiency should not receive live RV vaccine.

[Vaccine against human papilloma virus].

PubMed

Juárez-Albarrán, Alfredo César; Juárez-Gámez, Carlos Alberto

2008-01-01

Genital human papilloma virus infection (HPV) is the most common sexually transmitted infection worldwide, it is the cause of genital warts, and it is related with cervical cancer, the second most common cause of death from cancer in women in America, and the first in underdeveloped countries, and it is related with penis and prostate cancer in males also, and with anal cancer in both genders. This review examines the most important actual facts about HPV infection, and the new prophylactic vaccines. Two versions of the vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. One of them also targets HPV 6 and HPV 11, which account for approximately 90% of external genital warts. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. The role of men as carriers of HPV as well as vectors for transmission is well documented. Several clinical trials are currently under way to determine the efficacy of vaccinating men. Reducing the cost of vaccination would be a priority for the developing world in order to get a broad target in poor countries.

Potential targets for next generation antimicrobial glycoconjugate vaccines

PubMed Central

Micoli, Francesca; Costantino, Paolo; Adamo, Roberto

2018-01-01

Abstract Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell-dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines. Recent analysis from WHO/CHO underpins alarming concern toward antibiotic-resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad-spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated. This review analyzes structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines. PMID:29547971

Childhood varicella-zoster virus vaccination in Belgium

PubMed Central

Bilcke, Joke; Jan van Hoek, Albert; Beutels, Philippe

2013-01-01

Aim: To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 years. Methods: An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster.  Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys. Results and Conclusions: If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 years. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 years after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower. PMID:23321955

[Sexual risk behaviours and PAP testing in university women vaccinated against human papillomavirus].

PubMed

Fernández-Feito, Ana; Antón-Fernández, Raquel; Paz-Zulueta, María

2018-05-01

To estimate the association between the human papillomavirus (HPV) vaccine and sexual risk behaviour, as well as the participation in the Cervical Cancer Screening Program (CCSP). Cross-sectional study. School of Medicine and Health Sciences, School of Law, and School of Economics and Business (University of Oviedo). Female university students. Information was collected about contraceptive methods, sexual behaviours, HPV knowledge, and participation in the CCSP. Furthermore, proportions and odds ratio (OR) were estimated with their corresponding 95% confidence intervals (95%CI). Approximately two-thirds (67.7%) of the sample was vaccinated against HPV, and 216 women (65.3%) were sexually active. Barrier contraceptive methods were used by 67.6% during their current intimate relationships, being less frequent in non-vaccinated women (54.9% vs. 75.4% in vaccinated female students) (P=.002). The risk of having at least one sexual risk behaviour was higher in non-vaccinated women: OR2.29 (95%CI: 1.29-4.07). In addition, the probability of having a PAP test within the CCSP was higher in non-vaccinated women: OR2.18 (95%CI: 1.07-4.47). The prevalence of sexual risk behaviours in non-vaccinated women is elevated, and it is related to the lack of use of barrier contraceptive methods. The vaccination against HPV could affect sexual behaviours and the participation in the CCSP. Therefore, the information received by young people about contraceptive methods, sexually transmitted diseases, and cancer prevention should be reinforced. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Childhood varicella-zoster virus vaccination in Belgium: cost-effective only in the long run or without exogenous boosting?

PubMed

Bilcke, Joke; van Hoek, Albert Jan; Beutels, Philippe

2013-04-01

To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 y. An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster. Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys. If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 y. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 y after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower.

The path forward.

PubMed

De Gregorio, Ennio

2015-06-08

For many decades the only adjuvants accepted in human licensed vaccines have been particulate substances such as alum and emulsions. These compounds have been identified empirically, based on their ability to enhance immune responses to vaccination in animals, without understanding their mechanism of action. Thanks to the increased knowledge of the innate immune system, many new adjuvants, designed around known Pattern Recognition Receptors (PRRs) including Toll-like receptors (TLRs) have been identified. A TLR4 agonist is part of a licensed vaccine and TLR9 ligands are in late stage clinical testing. Adjuvants targeting alternative PRRs have been validated in preclinical models. In the future we have to expect more sophisticated adjuvant formulations, including multiple PPR ligands combined with novel antigen delivery systems. In addition to traditional adjuvants, other innovative strategies improving vaccine immunity are emerging. Among them combinations of vaccines with cytokines, inhibitors of metabolic pathways, modulators of baseline inflammation levels, monoclonal antibodies targeting checkpoint inhibitors and compounds depleting of regulatory cells. The introduction of novel technologies has the potential to support the development of vaccines with increased efficacy targeting infections as well as non-communicable diseases. However, the full potential of any novel vaccine strategy can be only captured if vaccination programs are implemented with sufficient coverage. New methods to fully capture the benefits of vaccination and appropriate communication strategies to increase vaccine acceptance by the public are two key elements that all stakeholders involved in the whole vaccine development cycle, including scientists, must consider very carefully. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

[Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico's Universal Vaccination Program].

PubMed

Hernández-Ávila, Mauricio; Lazcano-Ponce, Eduardo; Hernández-Ávila, Juan Eugenio; Alpuche-Aranda, Celia M; Rodríguez-López, Mario Henry; García-García, Lourdes; Madrid-Marina, Vicente; López Gatell-Ramírez, Hugo; Lanz-Mendoza, Humberto; Martínez-Barnetche, Jesús; Díaz-Ortega, José Luis; Ángeles-Llerenas, Angélica; Barrientos-Gutiérrez, Tonatiuh; Bautista-Arredondo, Sergio; Santos-Preciado, José Ignacio

2016-01-01

Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a) adequate vaccine efficacy against dengue virus (DENV) infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b) decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c) 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d) increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant questions that should be answered to properly assess the safety profile of the product and the target populations of potential benefit. In this regard we consider it would be informative to complete the 6-year follow-up after starting vaccination, according to the company's own study protocol recommended by the World Health Organization. As with any new vaccine, the potential licensing and implementation of the CYD-TDV as part of Mexico's vaccination program, requires a clear definition of the balance between the expected benefits and risks. Particularly with a vaccine with variable efficacy and some signs of risk, in the probable case of licensing, the post-licensed period must involve the development of detailed protocols to immediately identify risks or any health event associated with vaccination.

Seroprevalence of antibodies to measles and rubella eight months after a vaccination campaign in the southeast of Iran.

PubMed

Izadi, Shahrokh; Zahraei, Seyed Mohsen; Mokhtari-Azad, Talat

2018-02-08

Eight months after the mass immunization campaign of November 2015 against measles and rubella in the southeast of Iran, in order to evaluate the sero-immunity level of the people living in the mentioned region, a serosurvey study was performed. Using a multi-stage probability proportional to size cluster sampling, the sera of 1,056 participants, ranging from 15 months to 20 years old, were tested for measles and rubella IgG antibodies in the National Reference Laboratory at Tehran University of Medical Sciences, Tehran, Iran. The seroprevalence rates of antibodies against measles and rubella in the age groups below 16 years were respectively 98.4 and 93.2%. In the age group of 16 to 20 years, who was not the target of the mass immunization campaign, the said rates were respectively 91.7% and 87.4%. The herd immunity of the age groups below 16 years, who were the target of the campaign, is favourably high and reassuring both for measles and for rubella. Campaigns of supplementary vaccination play a substantial role for filling the gaps in the herd immunity.

Imported case of measles in a university setting leading to an outbreak of measles in Edinburgh, Scotland from September to December 2016.

PubMed

Kirolos, A; Waugh, C; Templeton, K; McCormick, D; Othieno, R; Willocks, L J; Stevenson, J

2018-04-01

In September 2016, an imported case of measles in Edinburgh in a university student resulted in a further 17 confirmed cases during October and November 2016. All cases were genotype D8 and were associated with a virus strain most commonly seen in South East Asia. Twelve of the 18 cases were staff or students at a university in Edinburgh and 17 cases had incomplete or unknown measles mumps rubella (MMR) vaccination status. The public health response included mass follow-up of all identified contacts, widespread communications throughout universities in Edinburgh and prompt vaccination clinics at affected campuses. Imported cases of measles pose a significant risk to university student cohorts who may be undervaccinated, include a large number of international students and have a highly mobile population. Public health departments should work closely with universities to promote MMR uptake and put in place mass vaccination plans to prevent rapidly spreading measles outbreaks in higher educational settings in future.

Alkylating chemotherapy may exert a uniquely deleterious effect upon neo-antigen-targeting anticancer vaccination

PubMed Central

Litterman, Adam J; Dudek, Arkadiusz Z; Largaespada, David A

2013-01-01

Alkylating chemotherapy exerts both antineoplastic and immunostimulatory effects. However, in addition to depleting regulatory T cells (Treg), alkylating agents also mediate a long lasting antiproliferative effect on responder lymphocytes. Our recent findings indicate that this antiproliferative effect profoundly impairs vaccination-induced immune responses, especially in the case of vaccines that target specific tumor-associated neo-antigens that do not require Treg depletion. PMID:24251080

76 FR 24031 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... Intervention to Promote a Targeted Vaccination program in the Obstetrician- Gynecologist Setting, FOA IP11-009... a Targeted Vaccination Program in the Obstetrician-Gynecologist Setting; FOA IP11-009, initial...

Intra-lymph node injection of biodegradable polymer particles.

PubMed

Andorko, James I; Tostanoski, Lisa H; Solano, Eduardo; Mukhamedova, Maryam; Jewell, Christopher M

2014-01-02

Generation of adaptive immune response relies on efficient drainage or trafficking of antigen to lymph nodes for processing and presentation of these foreign molecules to T and B lymphocytes. Lymph nodes have thus become critical targets for new vaccines and immunotherapies. A recent strategy for targeting these tissues is direct lymph node injection of soluble vaccine components, and clinical trials involving this technique have been promising. Several biomaterial strategies have also been investigated to improve lymph node targeting, for example, tuning particle size for optimal drainage of biomaterial vaccine particles. In this paper we present a new method that combines direct lymph node injection with biodegradable polymer particles that can be laden with antigen, adjuvant, or other vaccine components. In this method polymeric microparticles or nanoparticles are synthesized by a modified double emulsion protocol incorporating lipid stabilizers. Particle properties (e.g. size, cargo loading) are confirmed by laser diffraction and fluorescent microscopy, respectively. Mouse lymph nodes are then identified by peripheral injection of a nontoxic tracer dye that allows visualization of the target injection site and subsequent deposition of polymer particles in lymph nodes. This technique allows direct control over the doses and combinations of biomaterials and vaccine components delivered to lymph nodes and could be harnessed in the development of new biomaterial-based vaccines.

The Health Economic Impact of Universal Infant Vaccination with the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine as Compared with 13-Valent Pneumococcal Conjugate Vaccine in Hong Kong.

PubMed

Lee, Kenneth K C; Chia Wu, David Bin; Topachevskyi, Oleksandr; Delgleize, Emmanuelle; DeAntonio, Rodrigo

2013-05-01

Pneumococcal universal vaccination in Hong Kong was introduced in 2009. We assessed the health and economic impact of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PCV-10) compared with the current 13-valent pneumococcal conjugate vaccine (PCV-13) recommended for Hong Kong in 2011, providing new elements to be considered by public health authorities in the future decision-making process for pneumococcal vaccines in this country. An analytical model was used to estimate the annual economic and health outcomes of invasive pneumococcal disease (IPD), community-acquired pneumonia, and acute otitis media (AOM), including nontypeable H. influenzae-related AOM, for a birth cohort in Hong Kong from the payer perspective with a 10-year horizon. Clinical impact including morbidity-mortality, quality-adjusted life-years (QALYs), incremental costs, and cost-effectiveness comparing PCV-10 and PCV-13 were estimated. Probabilistic sensitivity analyses by using alternate scenarios were performed. Model projections indicate that PCV-13 and PCV-10 have approximately equivalent impact on the prevention of deaths caused by IPD and pneumonia. PCV-13 is projected to prevent 6 additional cases of IPD, whereas PCV-10 is projected to prevent 13,229 additional AOM cases and 101 additional QALYs. For the base case, PCV-10 vaccination is estimated to save 44.6 million Hong Kong dollars (34.1 million Hong Kong dollars discounted). Sensitivity analysis indicated that PCV-10 would generate more QALYs and save costs as compared with PCV-13. Universal infant vaccination with new available pneumococcal vaccines is expected to generate a significant additional impact on reducing the burden of pneumococcal diseases in Hong Kong. PCV-10 vaccination would be potentially a cost-saving strategy compared with PCV-13 vaccination, generating better cost offsets and higher QALY gains. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Genetic targeting of the active transcription factor XBP1s to dendritic cells potentiates vaccine-induced prophylactic and therapeutic antitumor immunity.

PubMed

Tian, Shenghe; Liu, Zuqiang; Donahue, Cara; Falo, Louis D; You, Zhaoyang

2012-02-01

In vivo dendritic cells (DC) targeting is an attractive approach with potential advantages in vaccine efficacy, cost, and availability. Identification of molecular adjuvants to in vivo "modulate " DC to coordinately render improved Th1 and CD8 T cell immunity, and attenuated deleterious Treg effects, is a critical challenge. Here, we report that in vivo genetic targeting of the active transcription factor XBP1s to DC (XBP1s/DC) potentiated vaccine-induced prophylactic and therapeutic antitumor immunity in multiple tumor models. This immunization strategy is based on a genetic vaccine encoding both cytomegalovirus (CMV)-driven vaccine Aghsp70 and DC-specific CD11c-driven XBP1s. The novel targeted vaccine induced durable Th1 and CD8 T cell responses to poorly immunogenic self/tumor antigen (Ag) and attenuated tumor-associated Treg suppressive function. Bone marrow (BM)-derived DC genetically modified to simultaneously overexpress XBP1s and express Aghsp70 upregulated CD40, CD70, CD86, interleukin (IL)-15, IL-15Rα, and CCR7 expression, and increased IL-6, IL-12, and tumor necrosis factor (TNF)-α production in vitro. XBP1s/DC elevated functional DEC205(+)CD8α(+)DC in the draining lymph nodes (DLN). The data suggest a novel role for XBP1s in modulating DC to potentiate tumor vaccine efficacy via overcoming two major obstacles to tumor vaccines (i.e., T cell hyporesponsiveness against poorly immunologic self/tumor Ag and tumor-associated Treg-mediated suppression) and improving DEC205(+)CD8α(+)DC.

COVER (cover of vaccination evaluated rapidly): description of the England and Wales scheme.

PubMed

Begg, N T; Gill, O N; White, J M

1989-03-01

The COVER scheme, a method for the rapid evaluation of vaccine coverage in England and Wales, is described. The primary aim of the scheme is to improve cover by providing health district vaccination programme coordinators with relevant timely information. Quarterly data were obtained from, analysed and promptly fed back to, 126 health districts on cohorts of children who had recently attained the target ages for receiving the selected sentinel vaccines; 18 months for third diphtheria and third pertussis and 2 years for measles. Although the data suggested that vaccination cover is improving, national performance still falls well short of 90%, the 1990 target set by the World Health Organisation for countries in Europe.

Proof of principle for epitope-focused vaccine design

PubMed Central

Correia, Bruno E.; Bates, John T.; Loomis, Rebecca J.; Baneyx, Gretchen; Carrico, Christopher; Jardine, Joseph G.; Rupert, Peter; Correnti, Colin; Kalyuzhniy, Oleksandr; Vittal, Vinayak; Connell, Mary J.; Stevens, Eric; Schroeter, Alexandria; Chen, Man; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Holmes, Margaret A.; Li, Yuxing; Klevit, Rachel E.; Graham, Barney S.; Wyatt, Richard T.; Baker, David; Strong, Roland K.; Crowe, James E.; Johnson, Philip R.; Schief, William R.

2014-01-01

Summary Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Multiple major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus (RSV), that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for research and development of a human RSV vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets including antigenically highly variable pathogens such as HIV and influenza. PMID:24499818

Humoral immunity targeting site I of antigenic domain 2 of glycoprotein B upon immunization with different cytomegalovirus candidate vaccines.

PubMed

Axelsson, Fredrika; Adler, Stuart P; Lamarre, Alain; Ohlin, Mats

2007-12-21

Glycoprotein B (gB) is a major component in several vaccines that are under development for prevention of disease by cytomegalovirus. It contains multiple determinants that are targets for neutralizing antibodies. One of them is site I of antigenic domain 2 (AD-2). The epitope, defined by short peptides, is quite conserved between different isolates. However, it is poorly immunogenic in natural infection. In this study we investigated the extent to which different vaccines, attenuated live Towne vaccine with or without priming with a canarypox virus coding for gB, or a recombinant gB vaccine adjuvanted with MF59, induced antibodies to this epitope. As in natural infection only a fraction of all subjects developed antibody responses against site I of AD-2 following vaccination. We suggest that strategies that enhance immunogenicity of this epitope will improve vaccine efficacy.

Proof of principle for epitope-focused vaccine design

NASA Astrophysics Data System (ADS)

Correia, Bruno E.; Bates, John T.; Loomis, Rebecca J.; Baneyx, Gretchen; Carrico, Chris; Jardine, Joseph G.; Rupert, Peter; Correnti, Colin; Kalyuzhniy, Oleksandr; Vittal, Vinayak; Connell, Mary J.; Stevens, Eric; Schroeter, Alexandria; Chen, Man; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Holmes, Margaret A.; Li, Yuxing; Klevit, Rachel E.; Graham, Barney S.; Wyatt, Richard T.; Baker, David; Strong, Roland K.; Crowe, James E.; Johnson, Philip R.; Schief, William R.

2014-03-01

Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.

Recent advances in microparticle and nanoparticle delivery vehicles for mucosal vaccination.

PubMed

McNeela, E A; Lavelle, E C

2012-01-01

The great potential of mucosal vaccination is widely accepted but progress in the clinical development of subunit mucosal vaccines has been disappointing. Of the available approaches, the use of polymer-based microparticles is attractive because these delivery vehicles can be specifically tailored for vaccines and they offer the potential for integration of adjuvant. Here we address recent developments in the use of particulates as mucosal vaccines and the potential of novel targeting strategies, formulation approaches and adjuvant combinations to enhance the efficacy of particle-based mucosal vaccines. This review discusses the current status of mucosal vaccines based on particles and highlights several of the strategies that are currently under investigation for improving their immunogenicity. These include enhancing the stability of formulations in the luminal environment, increasing uptake by specifically targeting particles to mucosal inductive sites, and augmenting immunogenicity through co-formulation with immunostimulatory agents.

Dengue Dynamics and Vaccine Cost-Effectiveness Analysis in the Philippines.

PubMed

Shim, Eunha

2016-11-02

Dengue is one of the most problematic vector-borne diseases in the Philippines, with an estimated 842,867 cases resulting in medical costs of $345 million U.S. dollars annually. In December 2015, the first dengue vaccine, known as chimeric yellow fever virus-dengue virus tetravalent dengue vaccine, was approved for use in the Philippines and is given to children 9 years of age. To estimate the cost-effectiveness of dengue vaccination in the Philippines, we developed an age-structured model of dengue transmission and vaccination. Using our model, we compared two vaccination scenarios entailing routine vaccination programs both with and without catch-up vaccination. Our results indicate that the higher the cost of vaccination, the less cost-effective the dengue vaccination program. With the current dengue vaccination program that vaccinates children 9 years of age, dengue vaccination is cost-effective for vaccination costs up to $70 from a health-care perspective and up to $75 from a societal perspective. Under a favorable scenario consisting of 1 year of catch-up vaccinations that target children 9-15 years of age, followed by regular vaccination of 9-year-old children, vaccination is cost-effective at costs up to $72 from a health-care perspective and up to $78 from a societal perspective. In general, dengue vaccination is expected to reduce the incidence of both dengue fever and dengue hemorrhagic fever /dengue shock syndrome. Our results demonstrate that even at relatively low vaccine efficacies, age-targeted vaccination may still be cost-effective provided the vaccination cost is sufficiently low. © The American Society of Tropical Medicine and Hygiene.

Dengue Dynamics and Vaccine Cost-Effectiveness Analysis in the Philippines

PubMed Central

Shim, Eunha

2016-01-01

Dengue is one of the most problematic vector-borne diseases in the Philippines, with an estimated 842,867 cases resulting in medical costs of $345 million U.S. dollars annually. In December 2015, the first dengue vaccine, known as chimeric yellow fever virus–dengue virus tetravalent dengue vaccine, was approved for use in the Philippines and is given to children 9 years of age. To estimate the cost-effectiveness of dengue vaccination in the Philippines, we developed an age-structured model of dengue transmission and vaccination. Using our model, we compared two vaccination scenarios entailing routine vaccination programs both with and without catch-up vaccination. Our results indicate that the higher the cost of vaccination, the less cost-effective the dengue vaccination program. With the current dengue vaccination program that vaccinates children 9 years of age, dengue vaccination is cost-effective for vaccination costs up to $70 from a health-care perspective and up to $75 from a societal perspective. Under a favorable scenario consisting of 1 year of catch-up vaccinations that target children 9–15 years of age, followed by regular vaccination of 9-year-old children, vaccination is cost-effective at costs up to $72 from a health-care perspective and up to $78 from a societal perspective. In general, dengue vaccination is expected to reduce the incidence of both dengue fever and dengue hemorrhagic fever /dengue shock syndrome. Our results demonstrate that even at relatively low vaccine efficacies, age-targeted vaccination may still be cost-effective provided the vaccination cost is sufficiently low. PMID:27601519

HIV vaccine development: would more (public) money bring quicker results?

PubMed

Winsbury, R

1999-01-01

Globally, $200-250 million/year are devoted to HIV vaccine research. Most of those funds pay for basic research rather than product development. Moreover, most of the funds are aimed at the HIV strain commonly found in the US and Europe, and not at the strains common to Africa and other developing countries. While US President Bill Clinton set in 1997 a 10-year target for the development of an HIV vaccine, that target date is looking increasingly unlikely. International vaccine and pharmaceutical companies typically drive vaccine research and development. However, concern over the ultimate profitability of developing and marketing an HIV vaccine, and the fear of major litigation should an eventual vaccine go awry have caused such firms to shy away from investing large amounts of money into HIV vaccine development. These companies somehow have to be attracted back into the field. A World Bank special task force is slated to present its report by mid-1999 on possible funding mechanisms to promote HIV vaccine development. It remains to be resolved whether public funds could and should be used, perhaps through a pooled international vaccine development fund. 2 new International AIDS Vaccine Initiative projects are described.

Trends in Meningococcal Disease Occurrences in the United States Military, 1971-2010

DTIC Science & Technology

2012-09-01

1982, a quadrivalent polysaccharide vaccine (MPSV-4; Menomune, Sanofi Pasteur, Bridgewater, NJ, USA) was introduced; this vaccine targets serogroups...regarding the performance of current vaccines. Of particular interest is the performance of the newer conjugate vaccine, MCV-4 (Menactra; Sanofi

The web and public confidence in MMR vaccination in Italy.

PubMed

Aquino, Francesco; Donzelli, Gabriele; De Franco, Emanuela; Privitera, Gaetano; Lopalco, Pier Luigi; Carducci, Annalaura

2017-08-16

Measles, mumps and rubella (MMR) vaccination coverage in Italy has been decreasing starting from 2012 and, at the present, none of the Italian regions has achieved the goal of 95% coverage target. A decision of the Court of Justice of Rimini in March 2012 that awarded vaccine-injury compensation for a case of autism has been indicated as a probable trigger event leading to a reduction of vaccine confidence in Italy. The aim of the study was to explore the relationship between MMR vaccination coverage to online search trends and social network activity on the topic "autism and MMR vaccine", during the period 2010-2015. A significant inverse correlation was found between MMR vaccination coverage and Internet search activity, tweets and Facebook posts. New media might have played a role in spreading misinformation. Media monitoring could be useful to assess the level of vaccine hesitancy and to plan and target effective information campaigns. Copyright © 2017 Elsevier Ltd. All rights reserved.

MUC1 and survivin combination tumor gene vaccine generates specific immune responses and anti-tumor effects in a murine melanoma model.

PubMed

Zhang, Haihong; Liu, Chenlu; Zhang, Fangfang; Geng, Fei; Xia, Qiu; Lu, Zhenzhen; Xu, Ping; Xie, Yu; Wu, Hui; Yu, Bin; Wu, Jiaxin; Yu, Xianghui; Kong, Wei

2016-05-23

MUC1 and survivin are ideal tumor antigens. Although many cancer vaccines targeting survivin or MUC1 have entered clinical trials, no vaccine combining MUC1 and survivin have been reported. Due to tumor heterogeneity, vaccines containing a combination of antigens may have improved efficacy and coverage of a broader spectrum of cancer targets. Here, cellular responses and anti-tumor activities induced by a combination of DNA vaccine targeting MUC1 and survivin (MS) were evaluated. Results showed that CTL activity and inhibition of tumor growth were obviously enhanced in mice immunized with the combined vaccine in a protection assay. However, in order to enhance the therapeutic effect in the treatment assay, a recombinant adenovirus (rAd) vaccine expressing MUC1 and survivin (Ad-MS) was used as a booster following the DNA vaccine prime. Meanwhile, IL-2 promoting T cell proliferation was used as an immunoadjuvant for the DNA vaccine. Results showed that the CTL activity response to the DNA vaccine was enhanced nearly 200% when boosted by the rAd vaccine and was further enhanced by nearly 60% when combined with the IL-2 adjuvant. Therefore, DNA prime combined with rAd boost and IL-2 (MS/IL2/Ad-MS) adjuvant was considered as the best strategy and further evaluated. Multiple cytokines promoting cellular immune responses were shown to be greatly enhanced in mice immunized with MS/IL2/Ad-MS. Moreover, in the treatment assay, the tumor inhibition rate of MS/IL2/Ad-MS reached up to 50.1%, which may be attributed to the enhancement of immune responses and reduction of immunosuppressive factors in tumor-bearing mice. These results suggested that immunization with the combination vaccine targeting MUC1 and survivin using a DNA prime-rAd boost strategy along with IL-2 adjuvant may be an effective method for breaking through immune tolerance to tumors expressing these antigens with potential therapeutic benefits in melanoma cancer. Copyright © 2016. Published by Elsevier Ltd.

Measles epidemic from 1951 to 2012 and vaccine effectiveness in Guangzhou, Southern China

PubMed Central

Yang, Zhicong; Xu, Jianxiong; Wang, Ming; Di, Biao; Tan, Huifeng; He, Qing; Cai, Yanshan; Liang, Jianhua; Hu, Wensui; Dong, Zhiqiang; Yang, Yunqing; Fu, Chuanxi

2014-01-01

Background Since the National Expanded Program on Immunization was implemented in China, considerable progress has been made in reducing the incidence of measles. However, the incidence of measles increased again in 2004. Few post-marketing studies on measles vaccine effectiveness were reported in China. In this study, we aimed to describe the measles epidemic and to evaluate the effectiveness of the measles vaccine in Guangzhou, southern China. Methods Based on the surveillance data for measles, we investigated the epidemiology during different periods between 1951 and 2012. We analyzed the clinical characteristics of laboratory-confirmed cases of measles between 2009 and 2012 and conducted a case-control study using test-negative cases as controls. We determined the protective effect of measles vaccine. Results The highest annual incidence in Guangzhou was 2187.15/100 000 in 1964, and the lowest was 0.32/100 000 in 2011. The average incidence of measles from 1951 to 2012 was 306.27/100 000. There was a significant tendency of decline in recent years. From 2009 to 2012, there are 700 laboratory-confirmed cases reported with an average onset age of 2.5 (median) years. The non-vaccinated target population (age <8 months and ≥15 years) accounted for 56.7% of the cases. The transient (non-resident) population accounted for 51.3% of the cases. Fewer cases were observed in the population targeted for measles vaccine (aged 8 months to 14 years). The effectiveness of a single dose of the measles vaccine was 89.1% (95% confidence interval (CI), 44.5–97.9), and the effectiveness of ≥2 doses of the measles vaccine was 97.8% (95% CI, 88.3–99.6) in children aged 8 months to 14 years old. Conclusions There is a significant overall decline in the incidence of measles (including clinical and laboratory confirmed cases) in the measles vaccine targeted population in Guangzhou. Two doses of measles vaccine are more effective than one dose in preventing measles in China. In order to accelerate the elimination of measles, vaccination should also be given to the transient and the non-vaccine targeted population. PMID:24513504

Theory-based development of an implementation intervention to increase HPV vaccination in pediatric primary care practices.

PubMed

Garbutt, Jane M; Dodd, Sherry; Walling, Emily; Lee, Amanda A; Kulka, Katharine; Lobb, Rebecca

2018-03-13

The national guideline for use of the vaccine targeting oncogenic strains of the human papillomavirus (HPV) is an evidence-based practice that is poorly implemented in primary care. Recommendations include completion of the vaccine series before the 13th birthday for girls and boys, giving the first dose at the 11- to 12-year-old check-up visit, concurrent with other recommended vaccines. Interventions to increase implementation of this guideline have had little impact, and opportunities to prevent cancer continue to be missed. We used a theory-informed approach to develop a pragmatic intervention for use in primary care settings to increase implementation of the HPV vaccine guideline recommendation. Using a concurrent mixed methods design in 10 primary care practices, we applied the Consolidated Framework for Implementation Research (CFIR) to systematically investigate and characterize factors strongly influencing vaccine use. We then used the Behavior Change Wheel (BCW) and the Theoretical Domains Framework (TDF) to analyze provider behavior and identify behaviors to target for change and behavioral change strategies to include in the intervention. We identified facilitators and barriers to guideline use across the five CFIR domains: most distinguishing factors related to provider characteristics, their perception of the intervention, and their process to deliver the vaccine. Targeted behaviors were for the provider to recommend the HPV vaccine the same way and at the same time as the other adolescent vaccines, to answer parents' questions with confidence, and to implement a vaccine delivery system. To this end, the intervention targeted improving provider's capability (knowledge, communication skills) and motivation (action planning, belief about consequences, social influences) regarding implementing guideline recommendations, and increasing their opportunity to do so (vaccine delivery system). Behavior change strategies included providing information and communication skill training with graded tasks and modeling, feedback of coverage rates, goal setting, and social support. These strategies were combined in an implementation intervention to be delivered using practice facilitation, educational outreach visits, and cyclical small tests of change. Using CFIR, the BCW and the TDF facilitated the development of a pragmatic, multi-component implementation intervention to increase use of the HPV vaccine in the primary care setting.

First Universities Allied for Essential Medicines (UAEM) Neglected Diseases and Innovation Symposium

PubMed Central

Musselwhite, Laura W.; Maciag, Karolina; Lankowski, Alex; Gretes, Michael C.; Wellems, Thomas E.; Tavera, Gloria; Goulding, Rebecca E.; Guillen, Ethan

2012-01-01

Universities Allied for Essential Medicines organized its first Neglected Diseases and Innovation Symposium to address expanding roles of public sector research institutions in innovation in research and development of biomedical technologies for treatment of diseases, particularly neglected tropical diseases. Universities and other public research institutions are increasingly integrated into the pharmaceutical innovation system. Academic entities now routinely undertake robust high-throughput screening and medicinal chemistry research programs to identify lead compounds for small molecule drugs and novel drug targets. Furthermore, product development partnerships are emerging between academic institutions, non-profit entities, and biotechnology and pharmaceutical companies to create diagnostics, therapies, and vaccines for diseases of the poor. With not for profit mission statements, open access publishing standards, open source platforms for data sharing and collaboration, and a shift in focus to more translational research, universities and other public research institutions are well-placed to accelerate development of medical technologies, particularly for neglected tropical diseases. PMID:22232453

Mass Media Campaign Impacts Influenza Vaccine Obtainment of University Students

ERIC Educational Resources Information Center

Shropshire, Ali M.; Brent-Hotchkiss, Renee; Andrews, Urkovia K.

2013-01-01

Objective: To describe the effectiveness of a mass media campaign in increasing the rate of college student influenza vaccine obtainment. Participants/Methods: Students ("N" = 721) at a large southern university completed a survey between September 2011 and January 2012 assessing what flu clinic media sources were visualized and if they…

Perceptions of HPV Vaccine amongst UK University Students

ERIC Educational Resources Information Center

Martin, Ellen; Senior, Naomi; Abdullah, Ammar; Brown, Janine; Collings, Suzanne; Racktoo, Sophie; Walpole, Sarah; Zeiton, Moez; Heffernan, Catherine

2011-01-01

Purpose: The aim of this small-scale focus group study is to explore the impact the Human Papilloma Virus (HPV) vaccine has on attitudes towards HPV, cervical cancer and sexual risk taking amongst university students in the UK. Design/methodology/approach: Participants were recruited through advertisements placed on notice boards throughout the…

Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for influenza vaccination in children

PubMed Central

2010-01-01

Background Influenza vaccination in infants and children with existing health complications is current practice in many countries, but healthy children are also susceptible to influenza, sometimes with complications. The under-recognised burden of disease in young children is greater than in elderly populations and the number of paediatric influenza cases reported does not reflect the actual frequency of influenza. Discussion Vaccination of healthy children is not widespread in Europe despite clear demonstration of the benefits of vaccination in reducing the large health and economic burden of influenza. Universal vaccination of infants and children also provides indirect protection in other high-risk groups in the community. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the vaccination of infants and children against influenza. The aim of CEVAG is to encourage the efficient and safe use of vaccines to prevent and control infectious diseases. Summary CEVAG recommends the introduction of universal influenza vaccination for all children from the age of 6 months. Special attention is needed for children up to 60 months of age as they are at greatest risk. Individual countries should decide on how best to implement this recommendation based on their circumstances. PMID:20546586

Optimizing targeted vaccination across cyber-physical networks: an empirically based mathematical simulation study.

PubMed

Mones, Enys; Stopczynski, Arkadiusz; Pentland, Alex 'Sandy'; Hupert, Nathaniel; Lehmann, Sune

2018-01-01

Targeted vaccination, whether to minimize the forward transmission of infectious diseases or their clinical impact, is one of the 'holy grails' of modern infectious disease outbreak response, yet it is difficult to achieve in practice due to the challenge of identifying optimal targets in real time. If interruption of disease transmission is the goal, targeting requires knowledge of underlying person-to-person contact networks. Digital communication networks may reflect not only virtual but also physical interactions that could result in disease transmission, but the precise overlap between these cyber and physical networks has never been empirically explored in real-life settings. Here, we study the digital communication activity of more than 500 individuals along with their person-to-person contacts at a 5-min temporal resolution. We then simulate different disease transmission scenarios on the person-to-person physical contact network to determine whether cyber communication networks can be harnessed to advance the goal of targeted vaccination for a disease spreading on the network of physical proximity. We show that individuals selected on the basis of their closeness centrality within cyber networks (what we call 'cyber-directed vaccination') can enhance vaccination campaigns against diseases with short-range (but not full-range) modes of transmission. © 2018 The Author(s).

Targeting C-type lectin receptors: a high-carbohydrate diet for dendritic cells to improve cancer vaccines

PubMed Central

van Dinther, Dieke; Stolk, Dorian A.; van de Ven, Rieneke; van Kooyk, Yvette; de Gruijl, Tanja D.; den Haan, Joke M. M.

2017-01-01

There is a growing understanding of why certain patients do or do not respond to checkpoint inhibition therapy. This opens new opportunities to reconsider and redevelop vaccine strategies to prime an anticancer immune response. Combination of such vaccines with checkpoint inhibitors will both provide the fuel and release the brake for an efficient anticancer response. Here, we discuss vaccine strategies that use C-type lectin receptor (CLR) targeting of APCs, such as dendritic cells and macrophages. APCs are a necessity for the priming of antigen-specific cytotoxic and helper T cells. Because CLRs are natural carbohydrate-recognition receptors highly expressed by multiple subsets of APCs and involved in uptake and processing of Ags for presentation, these receptors seem particularly interesting for targeting purposes. PMID:28729358

A universal vaccine for serogroup B meningococcus.

PubMed

Giuliani, Marzia M; Adu-Bobie, Jeannette; Comanducci, Maurizio; Aricò, Beatrice; Savino, Silvana; Santini, Laura; Brunelli, Brunella; Bambini, Stefania; Biolchi, Alessia; Capecchi, Barbara; Cartocci, Elena; Ciucchi, Laura; Di Marcello, Federica; Ferlicca, Francesca; Galli, Barbara; Luzzi, Enrico; Masignani, Vega; Serruto, Davide; Veggi, Daniele; Contorni, Mario; Morandi, Maurizio; Bartalesi, Alessandro; Cinotti, Vanda; Mannucci, Donatella; Titta, Francesca; Ovidi, Elisa; Welsch, Jo Anne; Granoff, Dan; Rappuoli, Rino; Pizza, Mariagrazia

2006-07-18

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood.

Chinese immigrant parents' vaccination decision making for children: a qualitative analysis.

PubMed

Wang, Linda D L; Lam, Wendy W T; Wu, Joseph T; Liao, Qiuyan; Fielding, Richard

2014-02-07

While immunization coverage rates for childhood routine vaccines in Hong Kong are almost 100%, the uptake rates of optional vaccines remain suboptimal. Understanding parental decision-making for children's vaccination is important, particularly among minority groups who are most vulnerable and underserved. This study explored how a subsample of new immigrant mothers from mainland China, a rapidly-growing subpopulation in Hong Kong, made decisions on various childhood and adolescent vaccines for their offspring, and identified key influences affecting their decision making. Semi-structured in-depth interviews were conducted with 23 Chinese new immigrant mothers recruited by purposive sampling. All interviews were audio-taped, transcribed and analyzed using a Grounded Theory approach. Participants' conversation revealed five underlying themes which influenced parents' vaccination decision-making: (1) Institutional factors, (2) Insufficient vaccination knowledge and advice, (3) Affective impacts on motivation, (4) Vaccination barriers, and (5) Social influences. The role of social norms appeared overwhelmingly salient influencing parents' vaccination decision making. Institutional factors shaped parent's perceptions of vaccination necessity. Fear of vaccine-targeted diseases was a key motivating factor for parents adopting vaccination. Insufficient knowledge about vaccines and targeted diseases, lack of advice from health professionals and, if provided, suspicions regarding the motivations for such advice were common issues. Vaccination cost was a major barrier for many new immigrant parents. Social norms play a key role influencing parental vaccination decision-making. Insight gained from this study will help inform healthcare providers in vaccination communication and policymakers in future vaccination programme.

Uptake and impact of vaccinating school age children against influenza during a season with circulation of drifted influenza A and B strains, England, 2014/15.

PubMed

Pebody, Richard G; Green, Helen K; Andrews, Nick; Boddington, Nicola L; Zhao, Hongxin; Yonova, Ivelina; Ellis, Joanna; Steinberger, Sophia; Donati, Matthew; Elliot, Alex J; Hughes, Helen E; Pathirannehelage, Sameera; Mullett, David; Smith, Gillian E; de Lusignan, Simon; Zambon, Maria

2015-01-01

The 2014/15 influenza season was the second season of roll-out of a live attenuated influenza vaccine (LAIV) programme for healthy children in England. During this season, besides offering LAIV to all two to four year olds, several areas piloted vaccination of primary (4-11 years) and secondary (11-13 years) age children. Influenza A(H3N2) circulated, with strains genetically and antigenically distinct from the 2014/15 A(H3N2) vaccine strain, followed by a drifted B strain. We assessed the overall and indirect impact of vaccinating school age children, comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot to non-pilot areas. Uptake levels were 56.8% and 49.8% in primary and secondary school pilot areas respectively. In primary school age pilot areas, cumulative primary care influenza-like consultation, emergency department respiratory attendance, respiratory swab positivity, hospitalisation and excess respiratory mortality were consistently lower in targeted and non-targeted age groups, though less for adults and more severe end-points, compared with non-pilot areas. There was no significant reduction for excess all-cause mortality. Little impact was seen in secondary school age pilot only areas compared with non-pilot areas. Vaccination of healthy primary school age children resulted in population-level impact despite circulation of drifted A and B influenza strains.

Constructing target product profiles (TPPs) to help vaccines overcome post-approval obstacles

PubMed Central

Lee, Bruce Y.; Burke, Donald S.

2012-01-01

As history has demonstrated, post-approval obstacles can impede a vaccine’s use and potentially lead to its withdrawal. Addressing these potential obstacles when changes in a vaccine’s technology can still be easily made may improve a vaccine’s chances of success. Augmented vaccine target product profiles (TPPs) can help vaccine scientists better understand and anticipate these obstacles and galvanize conversations among various vaccine stakeholders (e.g., scientists, marketers, business development managers, policy makers, public health officials, health care workers, third party payors, etc.) earlier in a vaccine’s development. PMID:19782109

Cost-Effectiveness Analysis of Universal Influenza Vaccination: Application of Susceptible-Infectious-Complication-Recovery Model.

PubMed

Yang, Kuen-Cheh; Hung, Hui-Fang; Chen, Meng-Kan; Chen, Li-Sheng; Fann, Jean Ching-Yuan; Chiu, Sherry Yueh-Hsia; Yen, Amy-Ming Fang; Huang, Kuo-Chin; Chen, Hsiu-Hsi; Wang, Sen-Te

2018-06-12

Despite the fact that vaccination is an effective primary prevention strategy for containing influenza outbreak, health policymakers show great concern over enormous costs involved in universal immunization particularly when resources are limited. We conducted a two-arm cost-effectiveness analysis (CEA) that takes into account the aspect of herd immunity, using a study cohort that was composed of 100,000 residents with the make-up of demographic characteristics identical to those of the underlying population in Taipei County, Taiwan, during the epidemic influenza season of 2001-2002. The parameters embedded in the dynamic process of infection were estimated by the application of the newly proposed susceptible-infection-complication-recovery model to the empirical data in order to compute the number of deaths and complications averted due to universal vaccination compared to non-vaccination. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curve (CEAC) given maximum amount of willingness-to-pay (WTP) were calculated to delineate the results of the two-arm CEA. Incremental costs involved in the vaccinated group as opposed to the unvaccinated group was $1,195 for reducing one additional complication and $805 for averting one additional death, allowing for herd immunity. The corresponding figures were higher for the results without considering herd immunity. Given the ceiling ratio of willingness-to-pay (WTP) equal to $10,000 (approximately two-thirds of the GDP), the probability of being cost-effective for vaccination was 100% and 96.7% for averting death and complications, respectively. Universal vaccination against seasonal influenza was very cost-effective particularly when herd immunity is considered. The probability of being cost-effective was almost certain given the maximum amount of WTP within two-thirds of the GDP. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Public Law 100-202, Joint Resolution making further continuing appropriations for the fiscal year 1988, and for other purposes, 22 December 1987.

PubMed

1988-01-01

This US Act provides the following with respect to universal access to child immunization: "The Congress calls upon the President to direct the Agency for International Development, working through the Centers for Disease Control and other appropriate Federal agencies, to work in a global effort to provide enhanced support towards achieving the goal of universal access to childhood immunization by 1990 by 1) assisting in the delivery, distribution, and use of vaccines, including a) the building of locally sustainable systems and technical capacities in developing countries to reach, by the appropriate age, not less than 80% of their annually projected target population with the full schedule of required immunizations and b) the development of a sufficient network of indigenous professionals and institutions with responsibility for developing, monitoring, and assessing immunization program and continually adapting strategies to reach the goal of preventing immunizable diseases and 2) performing, supporting, and encouraging research and development activities, in both the public and the private sector, that will be targeted at developing new vaccines and at modifying and improving existing vaccines to make them more appropriate for use in developing countries. In support of this global effort, the President should appeal to the people of the US and the US private sector to support public and private efforts to provide the resources necessary to achieve universal access to childhood immunization by 1990." The Act also does the following with respect to various forms of bilateral assistance: 1) prohibits the use of funds for an organization or program that supports coercive abortion or involuntary sterilization; 2) prohibits the use of funds for the performance of abortion as a method of family planning (FP); 3) provides that in awarding grants for natural FP under section 104 of the Foreign Assistance Act no applicant shall be discriminated against because of such applicant's religious or conscientious commitment to offer only natural FP. In addition, the Act stipulates that with respect to appropriations for the Department of Health and Human Services no funds will be used to perform abortions except where the life of the mother would be endangered if the fetus were carried to term. full text

Universal immunization in urban areas: Calcutta's success story.

PubMed

Chaudhuri, E R

1990-01-01

The Central Government of Calcutta, India aimed to immunize 85% (85,262) of the city's 12 month old infants against polio, diphtheria, measles, tuberculosis, pertussis and tetanus. The Universal Immunization Program (UIP) achieved this target 3 months earlier than intended. In fact, at the end of December 1990, it achieved 110.6% for DPT3, 142.16% for OPV3, 151.96% for BCG, and 97% for measles. UIP was able to surpass its targets by emphasizing team work. Government, the private sector, UNICEF, and the voluntary sector made up the Apex Coordination Committee on Immunization headed up by the mayor. The committee drafted an action plan which included routine immunization sessions on a fixed day and intensive immunization drives. Further the involved organizations pooled together cold chain equipment. In addition, the District Family Welfare Bureau was the distribution center for vaccines, syringes, immunization cards, report formats, vaccine carriers, and ice packs. Health workers administered immunizations from about 300 centers generally on Wednesday, National Immunization Day. Intensive immunization drives focused on measles immunizations. UIP leaders encouraged all center to routinely record coverage and submit monthly progress reports to the District Family Welfare Bureau. The Calcutta Municipal Corporation coordinated promotion activities and social mobilization efforts. Promotion included radio and TV announcements, newspaper advertisements, cinema slides, billboards, and posters. The original UIP plan to use professional communicators to mobilize communities was ineffective, so nongovernmental organizations entered the slums to encourage people to encourage their neighbors to immunize their children. Further Islamic, Protestant, and Catholic leaders encouraged the faithful to immunize their children. A UNICEF officer noted that this success must be sustained, however.

Epstein–barr virus vaccines

PubMed Central

Cohen, Jeffrey I

2015-01-01

Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis (IM) and is associated with epithelial cell malignancies such as nasopharyngeal carcinoma and gastric carcinoma, as well as lymphoid malignancies including Hodgkin lymphoma, Burkitt lymphoma, non-Hodgkin lymphoma and post-transplant lymphoproliferative disorder. EBV vaccines to prevent primary infection or disease, or therapeutic vaccines to treat EBV malignancies have not been licensed. Most efforts to develop prophylactic vaccines have focused on EBV gp350, which is the major target of neutralizing antibody. A single phase 2 trial of an EBV gp350 vaccine has been reported; the vaccine reduced the rate of IM but not virus infection. The observation that infusion of EBV-specific T cells can reduce disease due to Hodgkin lymphoma and nasopharyngeal carcinoma provides a proof of principle that a therapeutic vaccine for these and other EBV-associated malignancies might be effective. Most therapeutic vaccines have targeted EBV LMP2 and EBV nuclear antigen-1. As EBV is associated with nearly 200 000 new malignancies each year worldwide, an EBV vaccine to prevent these diseases is needed. PMID:25671130

Heterogeneity in the A33 protein impacts the cross-protective efficacy of a candidate smallpox DNA vaccine.

PubMed

Golden, Joseph W; Hooper, Jay W

2008-07-20

We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus proteins (A33, L1, B5, and A27). Because any subunit orthopoxvirus vaccine must protect against multiple species of orthopoxviruses, we are interested in understanding the cross-protective potential of our 4pox vaccine target immunogens. In our current studies, we focused on the A33 immunogen. We found one monoclonal antibody against A33, MAb-1G10, which could not bind the monkeypox virus A33 ortholog, A35. MAb-1G10 binding could be rescued if A35 amino acids 118 and 120 were substituted with those from A33. MAb-1G10 has been shown to protect mice from VACV challenge, thus our findings indicated a protective epitope differs among orthopoxviruses. Accordingly, we tested the cross-protective efficacy of a DNA vaccine consisting of A35R against VACV challenge and compared it to vaccination with A33R DNA. Mice vaccinated with A35R had greater mortality and more weight loss compared to those vaccinated with A33R. These findings demonstrate that despite high homology between A33R orthologs, amino acid differences can impact cross-protection. Furthermore, our results caution that adequate cross-protection by any pan-orthopoxvirus subunit vaccine will require not only careful evaluation of cross-protective immunity, but also of targeting of multiple orthopoxvirus immunogens.

Malaria vaccine R&D in the Decade of Vaccines: breakthroughs, challenges and opportunities.

PubMed

Birkett, Ashley J; Moorthy, Vasee S; Loucq, Christian; Chitnis, Chetan E; Kaslow, David C

2013-04-18

While recent progress has been made in reducing malaria mortality with other interventions, vaccines are still urgently needed to further reduce the incidence of clinical disease, including during pregnancy, and to provide "herd protection" by blocking parasite transmission. The most clinically advanced candidate, RTS,S, is presently undergoing Phase 3 evaluation in young African children across 13 clinical sites in eight African countries. In the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines. The development of more highly efficacious vaccines to prevent clinical disease caused by both P. falciparum and Plasmodium vivax, as well as vaccines to support elimination efforts by inducing immunity that blocks malaria parasite transmission, are priorities. Some key barriers to malaria vaccine development include: a paucity of well-characterized target immunogens and an absence of clear correlates of protection to enable vaccine development targeting all stages of the P. falciparum and P. vivax lifecycles; a limited number of safe and effective delivery systems, including adjuvants, that induce potent, long-lived protective immunity, be it by antibody, CD4+, and/or CD8+ T cell responses; and, for vaccines designed to provide "herd protection" by targeting sexual stage and/or mosquito antigens, the lack of a clear clinical and regulatory pathway to licensure using non-traditional endpoints. Recommendations to overcome these, and other key challenges, are suggested in this document. Copyright © 2013 Elsevier Ltd. All rights reserved.

Knowledge, Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands

PubMed Central

Burnett, Eleanor; Dalipanda, Tenneth; Ogaoga, Divi; Gaiofa, Jenny; Jilini, Gregory; Halpin, Alison; Dietz, Vance; Date, Kashmira; Mintz, Eric; Hyde, Terri; Wannemuehler, Kathleen; Yen, Catherine

2016-01-01

Background In response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1–15 years in selected communities in Choiseul and Western Provinces. Methodology and Principal Findings We conducted a post-vaccination campaign, household-level survey about knowledge, attitudes, and practices regarding diarrhea and cholera in areas targeted and not targeted for cholera vaccination. Respondents in vaccinated areas were more likely to have received cholera education in the previous 6 months (33% v. 9%; p = 0.04), to know signs and symptoms (64% vs. 22%; p = 0.02) and treatment (96% vs. 50%; p = 0.02) of cholera, and to be aware of cholera vaccine (48% vs. 14%; p = 0.02). There were no differences in water, sanitation, and hygiene practices. Conclusions This pre-emptive OCV campaign in a cholera-naïve community provided a unique opportunity to assess household-level knowledge, attitudes, and practices regarding diarrhea, cholera, and water, sanitation, and hygiene (WASH). Our findings suggest that education provided during the vaccination campaign may have reinforced earlier mass messaging about cholera and diarrheal disease in vaccinated communities. PMID:27548678

Economic burden of mucormycosis in the United States: can a vaccine be cost-effective?

PubMed

Ibrahim, Ashraf S; Edwards, John E; Bryant, Richard; Spellberg, Brad

2009-01-01

Mucormycosis is a life-threatening infection which causes unacceptably high morbidity and mortality despite treatment. Therefore, a vaccine to prevent mucormycosis is desirable. A major barrier to developing an anti-mucormycosis vaccine is the perception that such a vaccine would not be cost-effective to deploy because the disease is rare. We used data from a recent retrospective study to calculate the annual cost to the US healthcare system caused by mucormycosis infections. We created a model to estimate the cost-efficacy of a niche, anti-mucormycosis vaccine deployed in a targeted manner to high-risk patients. We found that each case of mucormycosis results in an average direct cost to the US healthcare system of $97,743, for an overall cost of mucormycosis of $50 million per year. In the base case scenario, targeted deployment of an anti-mucormycosis vaccine would result in a net cost per quality adjusted life year saved (QUALY) of $17,249. Variations in the price of the vaccine, its market penetration, or the cost of infection could dramatically decrease the net cost, and could even result in net savings per QUALY. In conclusion, mucormycosis causes considerable cost to the US health care system. Targeted deployment of a niche vaccine could decrease infection rates and mortality from mucormycosis in a cost-effective manner.

Development of a New DNA Vaccine for Alzheimer Disease Targeting a Wide Range of Aβ Species and Amyloidogenic Peptides

PubMed Central

Matsumoto, Yoh; Niimi, Naoko; Kohyama, Kuniko

2013-01-01

It has recently been determined that not only Aβ oligomers, but also other Aβ species and amyloidogenic peptides are neurotoxic in Alzheimer disease (AD) and play a pivotal role in AD pathogenesis. In the present study, we attempted to develop new DNA vaccines targeting a wide range of Aβ species. For this purpose, we first performed in vitro assays with newly developed vaccines to evaluate Aβ production and Aβ secretion abilities and then chose an IgL-Aβx4-Fc-IL-4 vaccine (designated YM3711) for further studies. YM3711 was vaccinated to mice, rabbits and monkeys to evaluate anti-Aβ species antibody-producing ability and Aβ reduction effects. It was found that YM3711 vaccination induced significantly higher levels of antibodies not only to Aβ1-42 but also to AD-related molecules including AβpE3-42, Aβ oligomers and Aβ fibrils. Importantly, YM3711 significantly reduced these Aβ species in the brain of model mice. Binding and competition assays using translated YM3711 protein products clearly demonstrated that a large part of antibodies induced by YM3711 vaccination are directed at conformational epitopes of the Aβ complex and oligomers. Taken together, we demonstrate that YM3711 is a powerful DNA vaccine targeting a wide range of AD-related molecules and is worth examining in preclinical and clinical trials. PMID:24086465

Review of the United States universal varicella vaccination program: Herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data

PubMed Central

Goldman, G.S.; King, P.G.

2013-01-01

In a cooperative agreement starting January 1995, prior to the FDA's licensure of the varicella vaccine on March 17, the Centers for Disease Control and Prevention (CDC) funded the Los Angeles Department of Health Services’ Antelope Valley Varicella Active Surveillance Project (AV-VASP). Since only varicella case reports were gathered, baseline incidence data for herpes zoster (HZ) or shingles was lacking. Varicella case reports decreased 72%, from 2834 in 1995 to 836 in 2000 at which time approximately 50% of children under 10 years of age had been vaccinated. Starting in 2000, HZ surveillance was added to the project. By 2002, notable increases in HZ incidence rates were reported among both children and adults with a prior history of natural varicella. However, CDC authorities still claimed that no increase in HZ had occurred in any US surveillance site. The basic assumptions inherent to the varicella cost–benefit analysis ignored the significance of exogenous boosting caused by those shedding wild-type VZV. Also ignored was the morbidity associated with even rare serious events following varicella vaccination as well as the morbidity from increasing cases of HZ among adults. Vaccine efficacy declined below 80% in 2001. By 2006, because 20% of vaccinees were experiencing breakthrough varicella and vaccine-induced protection was waning, the CDC recommended a booster dose for children and, in 2007, a shingles vaccination was approved for adults aged 60 years and older. In the prelicensure era, 95% of adults experienced natural chickenpox (usually as children)—these cases were usually benign and resulted in long-term immunity. Varicella vaccination is less effective than the natural immunity that existed in prevaccine communities. Universal varicella vaccination has not proven to be cost-effective as increased HZ morbidity has disproportionately offset cost savings associated with reductions in varicella disease. Universal varicella vaccination has failed to provide long-term protection from VZV disease. PMID:22659447

Influenza vaccinations and chemosensory function.

PubMed

Doty, Richard L; Berman, Austin H; Izhar, Mohammad; Hamilton, Hugh B; Villano, Danylko; Vazquez, Britney E; Warrum, Maja N; Mahbob, Mariam

2014-01-01

Although influenza vaccines have saved millions of lives, some have been associated with extremely rare adverse effects such as Guillain-Barré syndrome, Bell's palsy, and optic neuritis. Despite the fact that olfactory loss after an influenza vaccination is noted in one case report, no quantitative olfactory testing was performed. Hence, it is unclear whether, in fact, olfactory dysfunction can be associated with such vaccinations. This study was designed to (1) identify patients from the University of Pennsylvania Smell and Taste Center who attributed their empirically determined chemosensory disturbances to influenza vaccinations and (2) determine whether influenza vaccinations add to the degree of olfactory or gustatory dysfunction due to other causes. A retrospective analysis of self-reported etiologies of 4554 consecutive patients presenting to the University of Pennsylvania Smell and Taste Center with complaints of chemosensory dysfunction was performed. Those who reported dysfunction secondary to influenza vaccinations were identified. Additionally, in a subset of 925 patients for whom detailed inoculation histories were available, it was determined whether the number of lifetime inoculations added to the deficits due to other causes. Nine of the 4554 patients (0.19%) attributed olfactory disturbances to an influenza vaccination. None complained of taste dysfunction. All nine had abnormally low scores on the University of Pennsylvania Smell Identification Test (p < 0.001), with three being anosmic and six microsmic. Seven had elevated phenyl ethyl alcohol detection thresholds (p < 0.05). Two cases exhibited mild-to-moderate loss of whole mouth taste function. Of the 925 patients, no association was evident between the number of lifetime vaccinations and the chemosensory test scores. In accord with previous studies, age and sex were significantly related to the test scores. A very small percentage of the 4554 patients evaluated (0.19%) attributed their chemosensory dysfunction to a prior influenza vaccination. No influences of the number of lifetime influenza vaccinations on the test scores were evident in the subset of 925 patients whose dysfunction was due to other causes.

Use of surveillance data to identify target populations for Staphylococcus aureus vaccines and prevent surgical site infections: A pilot study

PubMed Central

Gustin, Marie-Paule; Giard, Marine; Bénet, Thomas; Vanhems, Philippe

2015-01-01

The development of anti-staphylococcal vaccines is nowadays a priority to prevent surgical site infections (SSI). The objective of the present study was to identify a potential target population by assessing surveillance data on surgery patients for possible anti-staphylococcal vaccine administration. Individuals at high risk of SSI by Staphylococcus aureus (SA) were targeted by the French SSI Surveillance Network in south-eastern France between 2008 and 2011. Among 238,470 patients, those undergoing primary total hip replacement appeared to be an interesting and healthy enough population for anti-staphylococcal vaccine testing. These male patients, subjected to multiple procedures and with American Society of Anesthesiologists score >2, had a probability of SA SSI about 21 times higher than females with no severe systemic disease and no multiple procedures. Our study indicates that surveillance data on SSI might be an interesting epidemiological source for planning vaccine trials to prevent nosocomial infections. PMID:25668663

Targeted Facebook Advertising is a Novel and Effective Method of Recruiting Participants into a Human Papillomavirus Vaccine Effectiveness Study

PubMed Central

Wark, John D; Tabrizi, Sepehr N; Garland, Suzanne M

2016-01-01

Background Targeted advertising using social networking sites (SNS) as a recruitment strategy in health research is in its infancy. Objective The aim of this study was to determine the feasibility of targeted Facebook advertisements to increase recruitment of unvaccinated women into a human papillomavirus (HPV) vaccine effectiveness study. Methods Between September 2011 and November 2013, females aged 18 to 25 years, residing in Victoria, Australia, were recruited through Facebook advertisements relating to general women’s health. From November 2013 to June 2015, targeted advertising campaigns were implemented to specifically recruit women who had not received the HPV vaccine. Consenting participants were invited to complete an online questionnaire and those who had ever had sexual intercourse were asked to provide a self-collected vaginal swab. The HPV vaccination status of participants was confirmed from the National HPV Vaccination Program Register (NHVPR). Results The campaign comprised 10 advertisements shown between September 2011 and June 2015 which generated 55,381,637 impressions, yielding 23,714 clicks, at an overall cost of AUD $22,078.85. A total of 919 participants were recruited. A greater proportion of unvaccinated women (50.4%, 131/260) were recruited into the study following targeted advertising, compared with those recruited (19.3%, 127/659) prior to showing the modified advertisement (P<.001). A greater proportion of the total sample completed tertiary education and resided in inner regional Victoria, compared with National population census data (P<.001), but was otherwise representative of the general population. Conclusions Targeted Facebook advertising is a rapid and cost-effective way of recruiting young unvaccinated women into a HPV vaccine effectiveness study. PMID:27450586

Targeted Facebook Advertising is a Novel and Effective Method of Recruiting Participants into a Human Papillomavirus Vaccine Effectiveness Study.

PubMed

Subasinghe, Asvini K; Nguyen, Margaret; Wark, John D; Tabrizi, Sepehr N; Garland, Suzanne M

2016-07-22

Targeted advertising using social networking sites (SNS) as a recruitment strategy in health research is in its infancy. The aim of this study was to determine the feasibility of targeted Facebook advertisements to increase recruitment of unvaccinated women into a human papillomavirus (HPV) vaccine effectiveness study. Between September 2011 and November 2013, females aged 18 to 25 years, residing in Victoria, Australia, were recruited through Facebook advertisements relating to general women's health. From November 2013 to June 2015, targeted advertising campaigns were implemented to specifically recruit women who had not received the HPV vaccine. Consenting participants were invited to complete an online questionnaire and those who had ever had sexual intercourse were asked to provide a self-collected vaginal swab. The HPV vaccination status of participants was confirmed from the National HPV Vaccination Program Register (NHVPR). The campaign comprised 10 advertisements shown between September 2011 and June 2015 which generated 55,381,637 impressions, yielding 23,714 clicks, at an overall cost of AUD $22,078.85. A total of 919 participants were recruited. A greater proportion of unvaccinated women (50.4%, 131/260) were recruited into the study following targeted advertising, compared with those recruited (19.3%, 127/659) prior to showing the modified advertisement (P<.001). A greater proportion of the total sample completed tertiary education and resided in inner regional Victoria, compared with National population census data (P<.001), but was otherwise representative of the general population. Targeted Facebook advertising is a rapid and cost-effective way of recruiting young unvaccinated women into a HPV vaccine effectiveness study.

Identifying vaccine targets for anti-leishmanial vaccine development

PubMed Central

Sundar, Shyam; Singh, Bhawana

2014-01-01

Leishmaniasis is a neglected tropical disease spread by an arthropod vector. It remains a significant health problem with an incidence of 0.2–0.4 million VL and 0.7–1.2 million CL cases each year. There are limitations associated with the current therapeutic regimens for leishmaniasis and the fact that after recovery from infection the host becomes immune to subsequent infection therefore, these factors forces the feasibility of a vaccine for leishmaniasis. Publication of the genome sequence of Leishmania has paved a new way to understand the pathogenesis and host immunological status therefore providing a deep insight in the field of vaccine research. This review is an effort to study the antigenic targets in Leishmania to develop anti-leishmanial vaccine. PMID:24606556

Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA Prime-Modified Vaccinia Virus Ankara Boost HIV-1 Vaccine Regimen.

PubMed

Bauer, Asli; Podola, Lilli; Mann, Philipp; Missanga, Marco; Haule, Antelmo; Sudi, Lwitiho; Nilsson, Charlotta; Kaluwa, Bahati; Lueer, Cornelia; Mwakatima, Maria; Munseri, Patricia J; Maboko, Leonard; Robb, Merlin L; Tovanabutra, Sodsai; Kijak, Gustavo; Marovich, Mary; McCormack, Sheena; Joseph, Sarah; Lyamuya, Eligius; Wahren, Britta; Sandström, Eric; Biberfeld, Gunnel; Hoelscher, Michael; Bakari, Muhammad; Kroidl, Arne; Geldmacher, Christof

2017-09-15

Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function, and specificity of Gag-specific T cells induced by a DNA-prime modified vaccinia virus Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding a subtype B and AB-recombinant Gag p37 and two vaccinations with MVA-CMDR encoding subtype A Gag p55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine-induced gamma interferon-positive (IFN-γ + ) Gag-specific T-cell responses were dominated by CD4 + T cells ( P < 0.001 compared to CD8 + T cells) that coexpressed interleukin-2 (IL-2) (66.4%) and/or tumor necrosis factor alpha (TNF-α) (63.7%). A median of 3 antigenic regions were targeted with a higher-magnitude median response to Gag p24 regions, more conserved between prime and boost, compared to those of regions within Gag p15 (not primed) and Gag p17 (less conserved; P < 0.0001 for both). Four regions within Gag p24 each were targeted by 45% to 74% of vaccinees upon restimulation with DNA-SMI-Gag matched peptides. The response rate to individual antigenic regions correlated with the sequence homology between the MVA- and DNA Gag-encoded immunogens ( P = 0.04, r 2 = 0.47). In summary, after the first MVA-CMDR boost, the sequence-mismatched DNA-prime MVA-boost vaccine strategy induced a Gag-specific T-cell response that was dominated by polyfunctional CD4 + T cells and that targeted multiple antigenic regions within the conserved Gag p24 protein. IMPORTANCE Genetic diversity is a major challenge for the design of vaccines against variable viruses. While including multiple variants for a given immunogen in prime-boost vaccination strategies is one approach that aims to improve coverage for global virus variants, the immunologic consequences of this strategy have been poorly defined so far. It is unclear whether inclusion of multiple variants in prime-boost vaccination strategies improves recognition of variant viruses by T cells and by which mechanisms this would be achieved, either by improved cross-recognition of multiple variants for a given antigenic region or through preferential targeting of antigenic regions more conserved between prime and boost. Engineering vaccines to induce adaptive immune responses that preferentially target conserved antigenic regions of viral vulnerability might facilitate better immune control after preventive and therapeutic vaccination for HIV and for other variable viruses. Copyright © 2017 American Society for Microbiology.

A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

PubMed Central

Choi, K. Yeon; Root, Matthew

2016-01-01

ABSTRACT Congenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In this disabled infectious single-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (the UL85 homolog GP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (105 PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P = 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy. IMPORTANCE Congenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. This disabled infectious single-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection. PMID:27334585

Financial Support to Eligible Countries for the Switch From Trivalent to Bivalent Oral Polio Vaccine-Lessons Learned.

PubMed

Shendale, Stephanie; Farrell, Margaret; Hampton, Lee M; Harris, Jennifer B; Kachra, Tasleem; Kurji, Feyrouz; Patel, Manish; Ramirez Gonzalez, Alejandro; Zipursky, Simona

2017-07-01

The global switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) ("the switch") presented an unprecedented challenge to countries. In order to mitigate the risks associated with country-level delays in implementing the switch, the Global Polio Eradication Initiative provided catalytic financial support to specific countries for operational costs unique to the switch. Between November 2015 and February 2016, a total of approximately US$19.4 million in financial support was provided to 67 countries. On average, country budgets allocated 20% to human resources, 23% to trainings and meetings, 8% to communications and advocacy, 9% to logistics, 15% to monitoring, and 5% to waste management. All 67 funded countries successfully switched from tOPV to bOPV during April-May 2016. This funding provided target countries with the necessary catalytic support to facilitate the execution of the switch on an accelerated timeline, and the mechanism offers a model for similar support to future global health efforts, such as the eventual global withdrawal of bOPV. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Measles Antibodies in Mother-Infant Dyads in Tianjin, China.

PubMed

Boulton, Matthew L; Wang, Xiexiu; Wagner, Abram L; Zhang, Ying; Carlson, Bradley F; Gillespie, Brenda W; Ding, Yaxing

2017-11-27

Many measles cases in Tianjin, China, occur in infants whose mothers were born after widespread vaccination programs. We assessed age-specific decreases in maternal measles antibodies in infants and examined maternal and infant characteristics in relation to infant antibody titers. Infant and mother dyads were enrolled from a sample of immunization clinics in all Tianjin districts. Participants' antibody titers were measured from dried blood spots. A multivariable log-linear model regressed infant antibody titers onto infant and mother characteristics. Among 551 infants aged ≤8 months, protective levels of measles antibodies were observed in infants whose mothers had measles titers ≥800 IU/mL (mean antibody titer, 542.5 IU/mL) or 400 to <800 IU/mL (mean, 202.2 IU/mL). Compared with infants whose mothers had no history of disease or vaccination, those with a history of disease had 1.60 times higher titers (95% confidence interval, 1.06-2.43). Limited vaccination programs in the 1980s have resulted in many Chinese women with inadequate protection against measles and an accordingly low efficiency of transplacental transmission to a fetus. Current vaccination programs, which target children aged 8 months through adolescence may be ineffective in controlling transmission of measles to infants. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Genome-level determination of Plasmodium falciparum blood-stage targets of malarial clinical immunity in the Peruvian Amazon.

PubMed

Torres, Katherine J; Castrillon, Carlos E; Moss, Eli L; Saito, Mayuko; Tenorio, Roy; Molina, Douglas M; Davies, Huw; Neafsey, Daniel E; Felgner, Philip; Vinetz, Joseph M; Gamboa, Dionicia

2015-04-15

Persons with blood-stage Plasmodium falciparum parasitemia in the absence of symptoms are considered to be clinically immune. We hypothesized that asymptomatic subjects with P. falciparum parasitemia would differentially recognize a subset of P. falciparum proteins on a genomic scale. Compared with symptomatic subjects, sera from clinically immune, asymptomatically infected individuals differentially recognized 51 P. falciparum proteins, including the established vaccine candidate PfMSP1. Novel, hitherto unstudied hypothetical proteins and other proteins not previously recognized as potential vaccine candidates were also differentially recognized. Genes encoding the proteins differentially recognized by the Peruvian clinically immune individuals exhibited a significant enrichment of nonsynonymous nucleotide variation, an observation consistent with these genes undergoing immune selection. A limited set of P. falciparum protein antigens was associated with the development of naturally acquired clinical immunity in the low-transmission setting of the Peruvian Amazon. These results imply that, even in a low-transmission setting, an asexual blood-stage vaccine designed to reduce clinical malaria symptoms will likely need to contain large numbers of often-polymorphic proteins, a finding at odds with many current efforts in the design of vaccines against asexual blood-stage P. falciparum. © 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.

Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA- (High Temperature Requirement A) Sterne Strain

PubMed Central

Chitlaru, Theodor; Israeli, Ma’ayan; Bar-Haim, Erez; Elia, Uri; Rotem, Shahar; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

2016-01-01

Anthrax is a lethal disease caused by the gram-positive spore-producing bacterium Bacillus anthracis. Live attenuated vaccines, such as the nonencapsulated Sterne strain, do not meet the safety standards mandated for human use in the Western world and are approved for veterinary purposes only. Here we demonstrate that disrupting the htrA gene, encoding the chaperone/protease HtrA (High Temperature Requirement A), in the virulent Bacillus anthracis Vollum strain results in significant virulence attenuation in guinea pigs, rabbits and mice, underlying the universality of the attenuated phenotype associated with htrA knockout. Accordingly, htrA disruption was implemented for the development of a Sterne-derived safe live vaccine compatible with human use. The novel B. anthracis SterneΔhtrA strain secretes functional anthrax toxins but is 10–104-fold less virulent than the Sterne vaccine strain depending on animal model (mice, guinea pigs, or rabbits). In spite of this attenuation, double or even single immunization with SterneΔhtrA spores elicits immune responses which target toxaemia and bacteremia resulting in protection from subcutaneous or respiratory lethal challenge with a virulent strain in guinea pigs and rabbits. The efficacy of the immune-protective response in guinea pigs was maintained for at least 50 weeks after a single immunization. PMID:26732659

Social regulations predispose people to complete vaccination for vaccine-preventable diseases.

PubMed

Takeuchi, Jiro; Goto, Masashi; Kawamura, Takashi; Hiraide, Atsushi

2014-11-01

Japan experienced measles outbreaks in both 2006 and 2007 mainly among university students. Improvement of vaccine coverage against vaccine-preventable viral infections is the prime task for preventing outbreaks of viral infections. To elucidate the promoting factors for complete vaccination against measles, rubella, mumps, and varicella-zoster viruses, we conducted a case-control study among single university students in Japan. Information on vaccinations and clinico-demographical factors were collected using a self-administered questionnaire and a photocopy of the Maternal and Child Health Handbook. Logistic regression analysis was performed to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for two-time vaccination against measles and rubella viruses as mandatory vaccinations and at least one-time vaccination against mumps and varicella-zoster viruses as optional vaccinations. A total of 1,370 (744 medical, 508 paramedical, and 118 pharmaceutical) students were invited to participate, 960 (70.1%) of whom were enrolled in the study. Students aged < 20 years had a greater propensity for measles and rubella vaccinations (OR 7.8 [95% CI, 5.1-11.8] and OR 6.1 [95% CI, 3.7-10.0], respectively) compared with those aged ≥ 20 years. Students with a history of living over-seas for 1 month or longer were more likely to complete vaccination for measles (OR 4.4 [95% CI, 1.4-13.5] compared with those without such history. This significantly high vaccination coverage was attributed to the measles-rubella catch-up campaign by the Japanese government and the immunization regulations by foreign countries. These findings suggest that social regulations would predispose people to complete vaccination.

Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates.

PubMed

Pearson, Mark S; Becker, Luke; Driguez, Patrick; Young, Neil D; Gaze, Soraya; Mendes, Tiago; Li, Xiao-Hong; Doolan, Denise L; Midzi, Nicholas; Mduluza, Takafira; McManus, Donald P; Wilson, R Alan; Bethony, Jeffrey M; Nausch, Norman; Mutapi, Francisca; Felgner, Philip L; Loukas, Alex

2015-01-01

Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well as previously uncharacterized proteins. Reactive IgG1 responses were not elevated in exposed individuals who did not acquire DIR. To complement our human subjects study, we screened for antigen targets of rhesus macaques rendered resistant to S. japonicum by experimental infection followed by self-cure, and discovered a number of new and known vaccine targets, including major targets recognized by our human subjects. This study has further validated the immunomics-based approach to schistosomiasis vaccine antigen discovery and identified numerous novel potential vaccine antigens.

DNA vaccines targeting the encoded antigens to dendritic cells induce potent antitumor immunity in mice.

PubMed

Cao, Jun; Jin, Yiqi; Li, Wei; Zhang, Bin; He, Yang; Liu, Hongqiang; Xia, Ning; Wei, Huafeng; Yan, Jian

2013-08-14

Although DNA vaccine holds a great potential for cancer immunotherapy, effective long-lasting antitumoral immunity sufficient to induce durable responses in cancer patients remains to be achieved. Considering the pivotal role of dendritic cells (DC) in the antigen processing and presentation, we prepared DC-targeting DNA vaccines by fusing tumor-associated antigen HER2/neu ectodomain to single chain antibody fragment (scFv) from NLDC-145 antibody specific for DC-restricted surface molecule DEC-205 (scFvNLDC-145), and explored its antitumoral efficacy and underlying mechanisms in mouse breast cancer models. In vivo targeting assay demonstrated that scFvNLDC-145 specifically delivered DNA vaccine-encoded antigen to DC. Compared with untargeted HER2/neu DNA vaccines, vaccination with scFvNLDC-145-HER2/neu markedly promoted the HER2/neu-specific cellular and humoral immune responses with long-lasting immune memory, resulting in effective protection against challenge of HER2/neu-positive D2F2/E2 breast tumor while ineffective in parental HER2/neu-negative D2F2 breast tumor. More importantly, in combination with temporary depletion of regulatory T cells (Treg) by low-dose cyclophosphamide, vaccination with scFvNLDC-145-HER2/neu induced the regression of established D2F2/E2 breast tumor and significantly retarded the development of spontaneous mammary carcinomas in transgenic BALB-neuT mice. Our findings demonstrate that DC-targeted DNA vaccines for in vivo direct delivery of tumor antigens to DC could induce potent antigen-specific cellular and humoral immune responses and, if additional combination with systemic Treg depletion, was able to elicit an impressively therapeutic antitumoral activity, providing a rationale for further development of this approach for cancer treatment.

Extended protection capabilities of an immature dendritic-cell targeting malaria sporozoite vaccine.

PubMed

Luo, Kun; Zavala, Fidel; Gordy, James; Zhang, Hong; Markham, Richard B

2017-04-25

Mouse studies evaluating candidate malaria vaccines have typically examined protective efficacy over the relatively short time frames of several weeks after the final of multiple immunizations. The current study examines the protective ability in a mouse model system of a novel protein vaccine construct in which the adjuvant polyinosinic polycytidilic acid (poly(I:C)) is used in combination with a vaccine in which the immature dendritic cell targeting chemokine, macrophage inflammatory protein 3 alpha (MIP3α), is fused to the circumsporozoite protein (CSP) of Plasmodium falciparum (P. falciparum). Two vaccinations, three weeks apart, elicited extraordinarily high, MIP3α-dependent antibody responses. MIP3α was able to target the vaccine to the CCR6 receptor found predominantly on immature dendritic cells and significantly enhanced the cellular influx at the vaccination site. At three and 23 weeks after the final of two immunizations, mice were challenged by intravenous injection of 5×10 3 transgenic Plasmodium berghei sporozoites expressing P. falciparum CSP, a challenge dose approximately one order of magnitude greater than that which is encountered after mosquito bite in the clinical setting. A ninety-seven percent reduction in liver sporozoite load was observed at both time points, 23 weeks being the last time point tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potential for Rabies Control through Dog Vaccination in Wildlife-Abundant Communities of Tanzania

PubMed Central

Fitzpatrick, Meagan C.; Hampson, Katie; Cleaveland, Sarah; Meyers, Lauren Ancel; Townsend, Jeffrey P.; Galvani, Alison P.

2012-01-01

Canine vaccination has been successful in controlling rabies in diverse settings worldwide. However, concerns remain that coverage levels which have previously been sufficient might be insufficient in systems where transmission occurs both between and within populations of domestic dogs and other carnivores. To evaluate the effectiveness of vaccination targeted at domestic dogs when wildlife also contributes to transmission, we applied a next-generation matrix model based on contract tracing data from the Ngorongoro and Serengeti Districts in northwest Tanzania. We calculated corresponding values of R 0, and determined, for policy purposes, the probabilities that various annual vaccination targets would control the disease, taking into account the empirical uncertainty in our field data. We found that transition rate estimates and corresponding probabilities of vaccination-based control indicate that rabies transmission in this region is driven by transmission within domestic dogs. Different patterns of rabies transmission between the two districts exist, with wildlife playing a more important part in Ngorongoro and leading to higher recommended coverage levels in that district. Nonetheless, our findings indicate that an annual dog vaccination campaign achieving the WHO-recommended target of 70% will control rabies in both districts with a high level of certainty. Our results support the feasibility of controlling rabies in Tanzania through dog vaccination. PMID:22928056

Vaccine-preventable disease and the under-utilization of immunizations in complex humanitarian emergencies.

PubMed

Close, Ryan M; Pearson, Catherine; Cohn, Jennifer

2016-09-07

Complex humanitarian emergencies affect 40-60 million people annually and are a growing public health concern worldwide. Despite efforts to provide medical and public health services to populations affected by complex emergencies, significant morbidity and mortality persist. Measles is a major communicable disease threat, but through vaccination of broader target age groups beyond the traditional immunization schedule, measles-related mortality has been significantly reduced during crises. Yet, a limited number of vaccine-preventable diseases continue to contribute disproportionately to morbidity and mortality in complex emergencies. The literature suggests that Streptococcus pneumoniae, Rotavirus, and Haemophilus influenzae type-b should be key targets for vaccination programs. Because of the significant contribution of these three pathogens to complex humanitarian emergencies in low and middle-income countries regardless of disaster type, geography, or population, their vaccines should be considered essential components of the standard emergency response effort. We discuss the barriers to vaccine distribution and provide evidence for strategies to improve distribution, including expanded target age-range and reduced dose schedules. Our review includes specific recommendations for the expanded use of these three vaccines in complex emergencies in low and middle-income countries as a way to guide future policy discussions. Copyright © 2016 Elsevier Ltd. All rights reserved.

2009-2010 Seasonal Influenza Vaccination Coverage among College Students from 8 Universities in North Carolina

ERIC Educational Resources Information Center

Poehling, Katherine A.; Blocker, Jill; Ip, Edward H.; Peters, Timothy R.; Wolfson, Mark

2012-01-01

Objective: The authors sought to describe the 2009-2010 seasonal influenza vaccine coverage of college students. Participants: A total of 4,090 college students from 8 North Carolina universities participated in a confidential, Web-based survey in October-November 2009. Methods: Associations between self-reported 2009-2010 seasonal influenza…

University Students' Knowledge and Attitudes Regarding Cervical Cancer, Human Papillomavirus, and Human Papillomavirus Vaccines in Turkey

ERIC Educational Resources Information Center

Koç, Zeliha

2015-01-01

Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…

Intent to Receive an HPV Vaccine among University Men and Women and Implications for Vaccine Administration

ERIC Educational Resources Information Center

Jones, Melissa; Cook, Robert

2008-01-01

Objective and Participants: In 2006, the authors examined intention to receive an HPV vaccine among 340 college students. Methods: A total of 138 men and 202 women completed questionnaires. The authors measured intention by asking participants how likely they would be to accept an HPV vaccine that prevented against (1) all HPV, (2) cervical cancer…

Safety of a Meningococcal Group B Vaccine Used in Response to Two University Outbreaks

ERIC Educational Resources Information Center

Duffy, Jonathan; Johnsen, Peter; Ferris, Mary; Miller, Mary; Leighton, Kevin; McGilvray, Mark; McNamara, Lucy; Breakwell, Lucy; Yu, Yon; Bhavsar, Tina; Briere, Elizabeth; Patel, Manisha

2017-01-01

Objective: To assess the safety of meningococcal group B (MenB)-4C vaccine. Participants: Undergraduates, dormitory residents, and persons with high-risk medical conditions received the MenB-4C vaccine two-dose series during mass vaccination clinics from 12/2013 through 11/2014. Methods: Adverse events (AEs) were identified by 15 minutes of…

Emerging influenza viruses and the prospect of a universal influenza virus vaccine.

PubMed

Krammer, Florian

2015-05-01

Influenza viruses cause annual seasonal epidemics and pandemics at irregular intervals. Several cases of human infections with avian and swine influenza viruses have been detected recently, warranting enhanced surveillance and the development of more effective countermeasures to address the pandemic potential of these viruses. The most effective countermeasure against influenza virus infection is the use of prophylactic vaccines. However, vaccines that are currently in use for seasonal influenza viruses have to be re-formulated and re-administered in a cumbersome process every year due to the antigenic drift of the virus. Furthermore, current seasonal vaccines are ineffective against novel pandemic strains. This paper reviews zoonotic influenza viruses with pandemic potential and technological advances towards better vaccines that induce broad and long lasting protection from influenza virus infection. Recent efforts have focused on the development of broadly protective/universal influenza virus vaccines that can provide immunity against drifted seasonal influenza virus strains but also against potential pandemic viruses. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

PubMed Central

Azizi, Ali; Kumar, Ashok; Diaz-Mitoma, Francisco; Mestecky, Jiri

2010-01-01

The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M) cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells. PMID:21085599

Uptake of influenza vaccination, awareness and its associated barriers among medical students of a University Hospital in Central Saudi Arabia.

PubMed

Abalkhail, Mohammed S; Alzahrany, Mohannad S; Alghamdi, Khaled A; Alsoliman, Muath A; Alzahrani, Mosa A; Almosned, Badr S; Gosadi, Ibrahim M; Tharkar, Shabana

Outbreaks of influenza epidemics are common but influenza vaccination is sub-optimal among the healthcare staff including the medical students. The study aims to assess the rate of vaccine uptake among medical students, its associated barriers and levels of awareness. A cross sectional study was done at a University Hospital in Saudi Arabia on 421 medical students by self administered questionnaire from February to March 2015. The immunization rate of seasonal influenza vaccine was just 20.7% in 2015, while it was 57% for cumulative of previous three-year period. The intended uptake among those offered vaccination was 68%. The significant determinants of vaccine uptake were clinical years of medical study (p<0.05) and previous history of vaccination (p<0.0001). The major sources influencing vaccine uptake decision were health department guidelines, medical training, social and media influence. Barriers of vaccination constituted, assumption of not being at risk of influenza (37.9%), vaccine side effects (28.9%), questioned effectiveness of the vaccine (14.5%), and inability to allocate time (11%). Knowledge levels were unsatisfactory and males scored lower (5.4±1.7) than females (6.5±1.4) out of total score of 9. Both knowledge and uptake of annual influenza vaccination was inadequate. Policy makers can formulate strategies with a focus on larger coverage of medical students. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

A qualitative analysis of factors influencing HPV vaccine uptake in Soweto, South Africa among adolescents and their caregivers.

PubMed

Katz, Ingrid T; Nkala, Busisiwe; Dietrich, Janan; Wallace, Melissa; Bekker, Linda-Gail; Pollenz, Kathryn; Bogart, Laura M; Wright, Alexi A; Tsai, Alexander C; Bangsberg, David R; Gray, Glenda E

2013-01-01

In South Africa, the prevalence of oncogenic Human Papillomavirus (HPV) may be as high as 64%, and cervical cancer is the leading cause of cancer-related death among women. The development of efficacious prophylactic vaccines has provided an opportunity for primary prevention. Given the importance of psycho-social forces in vaccine uptake, we sought to elucidate factors influencing HPV vaccination among a sample of low-income South African adolescents receiving the vaccine for the first time in Soweto. The HPV vaccine was introduced to adolescents in low-income townships throughout South Africa as part of a nationwide trial to understand adolescent involvement in future vaccine research targeting human immunodeficiency virus (HIV). We performed in-depth semi-structured interviews with purposively-sampled adolescents and their care providers to understand what forces shaped HPV vaccine uptake. Interviews were recorded, transcribed, translated, and examined using thematic analysis. Of 224 adolescents recruited, 201 initiated the vaccine; 192 (95.5%) received a second immunization; and 164 (81.6%) completed three doses. In our qualitative study of 39 adolescent-caregiver dyads, we found that factors driving vaccine uptake reflected a socio-cultural backdrop of high HIV endemnicity, sexual violence, poverty, and an abundance of female-headed households. Adolescents exercised a high level of autonomy and often initiated decision-making. Healthcare providers and peers provided support and guidance that was absent at home. The impact of the HIV epidemic on decision-making was substantial, leading participants to mistakenly conflate HPV and HIV. In a setting of perceived rampant sexual violence and epidemic levels of HIV, adolescents and caregivers sought to decrease harm by seeking a vaccine targeting a sexually transmitted infection (STI). Despite careful consenting, there was confusion regarding the vaccine's target. Future interventions promoting STI vaccines will need to provide substantial information for participants, particularly adolescents who may exercise a significant level of autonomy in decision-making.

Strategies to increase influenza vaccination rates: outcomes of a nationwide cross-sectional survey of UK general practice

PubMed Central

Teare, M Dawn; Dexter, Matthew; Siriwardena, A Niroshan; Read, Robert C

2012-01-01

Objective To identify practice strategies associated with higher flu vaccination rates in primary care. Design Logistic regression analysis of data from a cross-sectional online questionnaire. Setting 795 general practices across England. Participants 569 practice managers, 335 nursing staff and 107 general practitioners. Primary outcome measures Flu vaccination rates achieved by each practice in different groups of at-risk patients. Results 7 independent factors associated with higher vaccine uptake were identified. Having a lead staff member for planning the flu campaign and producing a written report of practice performance predicted an 8% higher vaccination rate for at-risk patients aged <65 years (OR 1.37, 95% CI 1.10 to 1.71). These strategies, plus sending a personal invitation to all eligible patients and only stopping vaccination when Quality and Outcomes Framework targets are reached, predicted a 7% higher vaccination rate (OR 1.45, 95% CI 1.10 to 1.92) in patients aged ≥65 years. Using a lead member of staff for identifying eligible patients, with either a modified manufacturer's or in-house search programme for interrogating the practice IT system, independently predicted a 4% higher vaccination rate in patients aged ≥65 years (OR 1.22, 95% CI 1.06 to 1.41/OR 1.20, 95% CI 1.03 to 1.40). The provision of flu vaccine by midwives was associated with a 4% higher vaccination rate in pregnant women (OR 1.19, 95% CI 1.02 to 1.40). Conclusions Clear leadership, effective communication about performance and methods used to identify and contact eligible patients were independently associated with significantly higher rates of flu vaccination. Financial targets appear to incentivise practices to work harder to maximise seasonal influenza vaccine uptake. The strategies identified here could help primary care providers to substantially increase their seasonal flu vaccination rates towards or even above the Chief Medical Officer's targets. PMID:22581793

Cancer and Stroma-Targeted Immunotherapy with a Genetically Modified DC Vaccine

DTIC Science & Technology

2011-05-01

targeting the tumor stroma in addition to breast cancer cells may produce the desired increase in antitumor activity of DC vaccines for breast cancer...vaccination inhibits 4T1-neu progression. We investigated whether DC-shA20-FAP- HER2 may induce more potent anti- stroma and anti-tumor immunity with the...the immunosuppressive tumor microenviroment resulting in potent antitumor activity. Zhu W, Zhou X, Rollins L , Rooney CM, Gottschalk S, Song XT

A dendritic cell targeted vaccine induces long-term HIV-specific immunity within the gastrointestinal tract.

PubMed

Ruane, D; Do, Y; Brane, L; Garg, A; Bozzacco, L; Kraus, T; Caskey, M; Salazar, A; Trumpheller, C; Mehandru, S

2016-09-01

Despite significant therapeutic advances for HIV-1 infected individuals, a preventative HIV-1 vaccine remains elusive. Studies focusing on early transmission events, including the observation that there is a profound loss of gastrointestinal (GI) CD4(+) T cells during acute HIV-1 infection, highlight the importance of inducing HIV-specific immunity within the gut. Here we report on the generation of cellular and humoral immune responses in the intestines by a mucosally administered, dendritic cell (DC) targeted vaccine. Our results show that nasally delivered α-CD205-p24 vaccine in combination with polyICLC, induced polyfunctional immune responses within naso-pulmonary lymphoid sites that disseminated widely to systemic and mucosal (GI tract and the vaginal epithelium) sites. Qualitatively, while α-CD205-p24 prime-boost immunization generated CD4(+) T-cell responses, heterologous prime-boost immunization with α-CD205-p24 and NYVAC gag-p24 generated high levels of HIV-specific CD4(+) and CD8(+) T cells within the GI tract. Finally, DC-targeting enhanced the amplitude and longevity of vaccine-induced immune responses in the GI tract. This is the first report of a nasally delivered, DC-targeted vaccine to generate HIV-specific immune responses in the GI tract and will potentially inform the design of preventative approaches against HIV-1 and other mucosal infections.

Mapping how information about childhood vaccination is communicated in two regions of Cameroon: What is done and where are the gaps?

PubMed

Ames, Heather; Njang, Diangha Mabel; Glenton, Claire; Fretheim, Atle; Kaufman, Jessica; Hill, Sophie; Oku, Afiong; Cliff, Julie; Cartier, Yuri; Bosch-Capblanch, Xavier; Rada, Gabriel; Muloliwa, Artur; Oyo-Ita, Angela; Lewin, Simon

2015-12-21

The 'Communicate to vaccinate' (COMMVAC) project builds research evidence for improving communication with parents and communities about childhood vaccinations in low- and middle-income countries. Understanding and mapping the range of vaccination communication strategies used in different settings is an important component of this work. In this part of the COMMVAC project, our objectives were: (1) to identify the vaccination communication interventions used in two regions of Cameroon; (2) to apply the COMMVAC taxonomy, a global taxonomy of vaccination communication interventions, to these communication interventions to help us classify these interventions, including their purposes and target audiences; and identify whether gaps in purpose or target audiences exist; (3) to assess the COMMVAC taxonomy as a research tool for data collection and analysis. We used the following qualitative methods to identify communication strategies in the Central and North West Regions of Cameroon in the first half of 2014: interviews with program managers, non-governmental organizations, vaccinators, parents and community members; observations and informal conversations during routine immunization clinics and three rounds of the National Polio Immunization Campaign; and document analysis of reports and mass media communications about vaccination. A survey of parents and caregivers was also done. We organised the strategies using the COMMVAC taxonomy and produced a map of Cameroon-specific interventions, which we presented to local stakeholders for feedback. Our map of the interventions used in Cameroon suggests that most childhood vaccination communication interventions focus on national campaigns against polio rather than routine immunisation. The map also indicates that most communication interventions target communities more broadly, rather than parents, and that very few interventions target health workers. The majority of the communication interventions aimed to inform or educate or remind or recall members of the community about vaccination. The COMMVAC taxonomy provided a useful framework for quickly and simply mapping existing vaccination communication strategies. By identifying the interventions used in Cameroon and developing an intervention map, we allowed stakeholders to see where they were concentrating their communication efforts and where gaps exist, allowing them to reflect on whether changes are needed to the communication strategies they are using.

Transport networks and inequities in vaccination: remoteness shapes measles vaccine coverage and prospects for elimination across Africa.

PubMed

Metcalf, C J E; Tatem, A; Bjornstad, O N; Lessler, J; O'Reilly, K; Takahashi, S; Cutts, F; Grenfell, B T

2015-05-01

Measles vaccination is estimated to have averted 13·8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (⩾50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered.

[Isolation and identification of Lyssavirus strains from an area of Slovakia where oral antirabies vaccine was administered].

PubMed

Ondrejka, R; Durove, A; Svrcek, S; Benísek, Z; Süliová, J

1997-02-01

The study was aimed at isolation and subsequent identification of strains of rabies virus by means of monoclonal antibodies from foxes killed in the vaccination zone within the complex preliminary monitoring of oral antirabies vaccination. The results obtained indicate that the vaccines for oral antirabies vaccination used in Slovakia did not contain any vaccination strain pathogenic to the extremely sensitive target species-the fox (Vulpes vulpes).

Clearing the Fog of Anticancer Patents from 1993–2013: Through an In-Depth Technology Landscape & Target Analysis from Pioneer Research Institutes and Universities Worldwide

PubMed Central

Dara, Ajay; Sangamwar, Abhay T.

2014-01-01

Background In a search for an effective anticancer therapy the R&D units from leading universities and institutes reveal numerous technologies in the form of patent documents. The article addressed comparative anticancer patent landscape and technology assessment of Council of Scientific and Industrial Research (CSIR): India’s largest R&D organisation with top twenty international public funded universities and institutes from eight different countries. Methodology/Principal Findings The methodology include quantitative and qualitative assessment based on the bibliometric parameters and manual technology categorisation to understand the changing patent trends and recent novel technologies. The research finding analysed 25,254 patent documents from the year 1993 to 2013 and reported the insights of latest anticancer technologies and targets through categorisation studies at the level of drug discovery, development and treatment & diagnosis. The article has reported the technology correlation matrix of twelve secondary class technologies with 34 tertiary sub-class research area to identify the leading technologies and scope of future research through whitespaces analysis. In addition, the results have also addressed the target analysis, leading inventor, assignee, collaboration network, geographical distribution, patent trend analysis, citation maps and technology assessment with respect to international patent classification systems such as CPC, IPC and CPI codes. Conclusions/Significance The result suggested peptide technology as the dominating research area next to gene therapy, vaccine and medical preparation containing organic compounds. The Indian CSIR has ranked itself at seventh position among the top 20 universities. Globally, the anticancer research was focused in the area of genetics and immunology, whereas Indian CSIR reported more patents related to plant extract and organic preparation. The article provided a glimpse of two decade anticancer scenario with respect to top public funded universities worldwide. PMID:25083710

Clearing the fog of anticancer patents from 1993-2013: through an in-depth technology landscape & target analysis from pioneer research institutes and universities worldwide.

PubMed

Dara, Ajay; Sangamwar, Abhay T

2014-01-01

In a search for an effective anticancer therapy the R&D units from leading universities and institutes reveal numerous technologies in the form of patent documents. The article addressed comparative anticancer patent landscape and technology assessment of Council of Scientific and Industrial Research (CSIR): India's largest R&D organisation with top twenty international public funded universities and institutes from eight different countries. The methodology include quantitative and qualitative assessment based on the bibliometric parameters and manual technology categorisation to understand the changing patent trends and recent novel technologies. The research finding analysed 25,254 patent documents from the year 1993 to 2013 and reported the insights of latest anticancer technologies and targets through categorisation studies at the level of drug discovery, development and treatment & diagnosis. The article has reported the technology correlation matrix of twelve secondary class technologies with 34 tertiary sub-class research area to identify the leading technologies and scope of future research through whitespaces analysis. In addition, the results have also addressed the target analysis, leading inventor, assignee, collaboration network, geographical distribution, patent trend analysis, citation maps and technology assessment with respect to international patent classification systems such as CPC, IPC and CPI codes. The result suggested peptide technology as the dominating research area next to gene therapy, vaccine and medical preparation containing organic compounds. The Indian CSIR has ranked itself at seventh position among the top 20 universities. Globally, the anticancer research was focused in the area of genetics and immunology, whereas Indian CSIR reported more patents related to plant extract and organic preparation. The article provided a glimpse of two decade anticancer scenario with respect to top public funded universities worldwide.

Chinese immigrant parents’ vaccination decision making for children: a qualitative analysis

PubMed Central

2014-01-01

Background While immunization coverage rates for childhood routine vaccines in Hong Kong are almost 100%, the uptake rates of optional vaccines remain suboptimal. Understanding parental decision-making for children’s vaccination is important, particularly among minority groups who are most vulnerable and underserved. This study explored how a subsample of new immigrant mothers from mainland China, a rapidly-growing subpopulation in Hong Kong, made decisions on various childhood and adolescent vaccines for their offspring, and identified key influences affecting their decision making. Methods Semi-structured in-depth interviews were conducted with 23 Chinese new immigrant mothers recruited by purposive sampling. All interviews were audio-taped, transcribed and analyzed using a Grounded Theory approach. Results Participants’ conversation revealed five underlying themes which influenced parents’ vaccination decision-making: (1) Institutional factors, (2) Insufficient vaccination knowledge and advice, (3) Affective impacts on motivation, (4) Vaccination barriers, and (5) Social influences. The role of social norms appeared overwhelmingly salient influencing parents’ vaccination decision making. Institutional factors shaped parent’s perceptions of vaccination necessity. Fear of vaccine-targeted diseases was a key motivating factor for parents adopting vaccination. Insufficient knowledge about vaccines and targeted diseases, lack of advice from health professionals and, if provided, suspicions regarding the motivations for such advice were common issues. Vaccination cost was a major barrier for many new immigrant parents. Conclusions Social norms play a key role influencing parental vaccination decision-making. Insight gained from this study will help inform healthcare providers in vaccination communication and policymakers in future vaccination programme. PMID:24507384

Vaccination Coverage Disparities Between Foreign-Born and U.S.-Born Children Aged 19-35 Months, United States, 2010-2012.

PubMed

Varan, Aiden K; Rodriguez-Lainz, Alfonso; Hill, Holly A; Elam-Evans, Laurie D; Yankey, David; Li, Qian

2017-08-01

Healthy People 2020 targets high vaccination coverage among children. Although reductions in coverage disparities by race/ethnicity have been described, data by nativity are limited. The National Immunization Survey is a random-digit-dialed telephone survey that estimates vaccination coverage among U.S. children aged 19-35 months. We assessed coverage among 52,441 children from pooled 2010-2012 data for individual vaccines and the combined 4:3:1:3*:3:1:4 series (which includes ≥4 doses of diphtheria, tetanus, and acellular pertussis vaccine/diphtheria and tetanus toxoids vaccine/diphtheria, tetanus toxoids, and pertussis vaccine, ≥3 doses of poliovirus vaccine, ≥1 dose of measles-containing vaccine, ≥3 or ≥4 doses of Haemophilus influenzae type b vaccine (depending on product type of vaccine; denoted as 3* in the series name), ≥3 doses of hepatitis B vaccine, ≥1 dose of varicella vaccine, and ≥4 doses of pneumococcal conjugate vaccine). Coverage estimates controlling for sociodemographic factors and multivariable logistic regression modeling for 4:3:1:3*:3:1:4 series completion are presented. Significantly lower coverage among foreign-born children was detected for DTaP, hepatitis A, hepatitis B, Hib, pneumococcal conjugate, and rotavirus vaccines, and for the combined series. Series completion disparities persisted after control for demographic, access-to-care, poverty, and language effects. Substantial and potentially widening disparities in vaccination coverage exist among foreign-born children. Improved immunization strategies targeting this population and continued vaccination coverage monitoring by nativity are needed.

Role of the private sector in vaccination service delivery in India: evidence from private-sector vaccine sales data, 2009-12.

PubMed

Sharma, Abhishek; Kaplan, Warren A; Chokshi, Maulik; Zodpey, Sanjay P

2016-09-01

India's Universal Immunization Programme (UIP) provides basic vaccines free-of-cost in the public sector, yet national vaccination coverage is poor. The Government of India has urged an expanded role for the private sector to help achieve universal immunization coverage. We conducted a state-by-state analysis of the role of the private sector in vaccinating Indian children against each of the six primary childhood diseases covered under India's UIP. We analyzed IMS Health data on Indian private-sector vaccine sales, 2011 Indian Census data and national household surveys (DHS/NFHS 2005-06 and UNICEF CES 2009) to estimate the percentage of vaccinated children among the 2009-12 birth cohort who received a given vaccine in the private sector in 16 Indian states. We also analyzed the estimated private-sector vaccine shares as function of state-specific socio-economic status. Overall in 16 states, the private sector contributed 4.7% towards tuberculosis (Bacillus Calmette-Guérin (BCG)), 3.5% towards measles, 2.3% towards diphtheria-pertussis-tetanus (DPT3) and 7.6% towards polio (OPV3) overall (both public and private sectors) vaccination coverage. Certain low income states (Uttar Pradesh, Rajasthan, Madhya Pradesh, Orissa, Assam and Bihar) have low private as well as public sector vaccination coverage. The private sector's role has been limited primarily to the high income states as opposed to these low income states where the majority of Indian children live. Urban areas with good access to the private sector and the ability to pay increases the Indian population's willingness to access private-sector vaccination services. In India, the public sector offers vaccination services to the majority of the population but the private sector should not be neglected as it could potentially improve overall vaccination coverage. The government could train and incentivize a wider range of private-sector health professionals to help deliver the vaccines, especially in the low income states with the largest birth cohorts. We recommend future studies to identify strengths and limitations of the public and private health sectors in each Indian state. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinician and Parent Perspectives on Educational Needs for Increasing Adolescent HPV Vaccination.

PubMed

Widman, Christy A; Rodriguez, Elisa M; Saad-Harfouche, Frances; Twarozek, Annamaria Masucci; Erwin, Deborah O; Mahoney, Martin C

2018-04-01

Human papillomavirus (HPV)-related morbidity and mortality remain a significant public health burden despite the availability of HPV vaccines for cancer prevention. We engaged clinicians and parents to identify barriers and opportunities related to adolescent HPV vaccination within a focused geographic region. This mixed-method study design used an interviewer-administered semi-structured interview with clinicians (n = 52) and a written self-administered survey with similar items completed by parents (n = 54). Items focused on experiences, opinions, and ideas about HPV vaccine utilization in the clinical setting, family, and patient perceptions about HPV vaccination and potential future efforts to increase vaccine utilization. Quantitative items were analyzed using descriptive statistics, while qualitative content was analyzed thematically. Suggested solutions for achieving higher rates of HPV vaccination noted by clinicians included public health education, the removal of stigma associated with vaccines, media endorsements, and targeting parents as the primary focus of educational messages. Parents expressed the need for more information about HPV-related disease, HPV vaccines, vaccine safety, sexual concerns, and countering misinformation on social media. Results from this mixed-method study affirm that educational campaigns targeting both health care professionals and parents represent a key facilitator for promoting HPV vaccination; disease burden and cancer prevention emerged as key themes for this messaging.

Progress in the Development of a Cervical Cancer Vaccine

PubMed Central

Winters, Ursula; Roden, Richard; Kitchener, Henry; Stern, Peter

2006-01-01

Persistent infection by ‘high risk’ genotypes of human papilloma virus (HPV) is necessary but not sufficient for the development of over 98% of cervical cancers. Thus the development of vaccines that prevent HPV transmission represent an important opportunity to prevent cervical cancer. There are several prophylactic HPV vaccine formulations based upon L1 virus-like particles (VLPs) currently in phase III trials and recently released data are extremely promising. However, many practical issues surrounding implementation of these vaccines need to be addressed including, who and when to vaccinate, duration of protection, and integration with current screening programs. The vaccines currently being evaluated target the two most prevalent high risk HPV types which are responsible for approximately 70% of cervical cancers. To increase the breadth of protection, it is likely that L1 VLPs of other viral subtypes must be included, although vaccines targeting the conserved regions of the L2 minor capsid protein warrant further exploration in this regard. In addition the vaccines nearing licensing will not combat established HPV-related disease and a therapeutic vaccine, of which there are several candidates in early stages of development, would be desirable. This review discusses the background to and progress in vaccine development and the issues surrounding the introduction of HPV vaccines. PMID:18360601

A universal vaccine for serogroup B meningococcus

PubMed Central

Giuliani, Marzia M.; Adu-Bobie, Jeannette; Comanducci, Maurizio; Aricò, Beatrice; Savino, Silvana; Santini, Laura; Brunelli, Brunella; Bambini, Stefania; Biolchi, Alessia; Capecchi, Barbara; Cartocci, Elena; Ciucchi, Laura; Di Marcello, Federica; Ferlicca, Francesca; Galli, Barbara; Luzzi, Enrico; Masignani, Vega; Serruto, Davide; Veggi, Daniele; Contorni, Mario; Morandi, Maurizio; Bartalesi, Alessandro; Cinotti, Vanda; Mannucci, Donatella; Titta, Francesca; Ovidi, Elisa; Welsch, Jo Anne; Granoff, Dan; Rappuoli, Rino; Pizza, Mariagrazia

2006-01-01

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood. PMID:16825336

New Generation of Inactivated Poliovirus Vaccines for Universal Immunization After Eradication of Poliomyelitis

PubMed Central

Chumakov, Konstantin; Ehrenfeld, Ellie

2008-01-01

Twenty years of global polio eradication efforts may soon eliminate wild-type poliovirus transmission. However, new information about poliovirus learned during this campaign, as well as the political realities of a modern world demand that universal immunity against poliomyelitis be maintained even after wild poliovirus is eradicated. Although two excellent vaccines have proven highly effective in the past, neither the live nor current inactivated products are optimal for use in the post-eradication setting. Therefore, concerted efforts are urgently needed to develop a new generation of vaccine that is risk-free and affordable and can be produced on a global scale. Here we discuss the desired properties and ways to create a new polio vaccine. PMID:18990066

Hepatitis B Virus Infection in Indonesia 15 Years After Adoption of a Universal Infant Vaccination Program: Possible Impacts of Low Birth Dose Coverage and a Vaccine-Escape Mutant.

PubMed

Purwono, Priyo Budi; Juniastuti; Amin, Mochamad; Bramanthi, Rendra; Nursidah; Resi, Erika Maria; Wahyuni, Rury Mega; Yano, Yoshihiko; Soetjipto; Hotta, Hak; Hayashi, Yoshitake; Utsumi, Takako; Lusida, Maria Inge

2016-09-07

A universal hepatitis B vaccination program for infants was adopted in Indonesia in 1997. Before its implementation, the prevalence of hepatitis B surface antigen (HBsAg)-positive individuals in the general population was approximately 5-10%. The study aimed to investigate the hepatitis B virus (HBV) serological status and molecular profile among children, 15 years after adoption of a universal infant vaccination program in Indonesia. According to the Local Health Office data in five areas, the percentages of children receiving three doses of hepatitis B vaccine are high (73.9-94.1%), whereas the birth dose coverage is less than 50%. Among 967 children in those areas, the seropositive rate of HBsAg in preschool- and school-aged children ranged from 2.1% to 4.2% and 0% to 5.9%, respectively. Of the 61 HBV DNA-positive samples, the predominant genotype/subtype was B/adw2 Subtype adw3 was identified in genotype C for the first time in this population. Six samples (11.5%) had an amino acid substitution within the a determinant of the S gene region, and one sample had T140I that was suggested as a vaccine-escape mutant type. The low birth dose coverage and the presence of a vaccine-escape mutant might contribute to the endemicity of HBV infection among children in Indonesia. © The American Society of Tropical Medicine and Hygiene.

Hepatitis B Virus Infection in Indonesia 15 Years after Adoption of a Universal Infant Vaccination Program: Possible Impacts of Low Birth Dose Coverage and a Vaccine-Escape Mutant

PubMed Central

Purwono, Priyo Budi; Juniastuti; Amin, Mochamad; Bramanthi, Rendra; Nursidah; Resi, Erika Maria; Wahyuni, Rury Mega; Yano, Yoshihiko; Soetjipto; Hotta, Hak; Hayashi, Yoshitake; Utsumi, Takako; Lusida, Maria Inge

2016-01-01

A universal hepatitis B vaccination program for infants was adopted in Indonesia in 1997. Before its implementation, the prevalence of hepatitis B surface antigen (HBsAg)–positive individuals in the general population was approximately 5–10%. The study aimed to investigate the hepatitis B virus (HBV) serological status and molecular profile among children, 15 years after adoption of a universal infant vaccination program in Indonesia. According to the Local Health Office data in five areas, the percentages of children receiving three doses of hepatitis B vaccine are high (73.9–94.1%), whereas the birth dose coverage is less than 50%. Among 967 children in those areas, the seropositive rate of HBsAg in preschool- and school-aged children ranged from 2.1% to 4.2% and 0% to 5.9%, respectively. Of the 61 HBV DNA–positive samples, the predominant genotype/subtype was B/adw2. Subtype adw3 was identified in genotype C for the first time in this population. Six samples (11.5%) had an amino acid substitution within the a determinant of the S gene region, and one sample had T140I that was suggested as a vaccine-escape mutant type. The low birth dose coverage and the presence of a vaccine-escape mutant might contribute to the endemicity of HBV infection among children in Indonesia. PMID:27402524

Survey of rabies vaccination status of Queensland veterinarians and veterinary students.

PubMed

Mendez, D; Foyle, L; Cobbold, R; Speare, R

2018-05-01

To determine the rabies vaccination status of Queensland veterinarians and veterinary students and their perception of zoonotic risk from Australian bat lyssavirus (ABLV). Cross-sectional questionnaire surveys. Questionnaires were sent by post in 2011 to veterinary surgeons registered in Queensland, to final-year veterinary students at James Cook University via SurveyMonkey® in 2013 and to final-year veterinary students at James Cook University and University of Queensland via SurveyMonkey® in 2014. The response rate for registered veterinarians was 33.5% and for veterinary students 33.3% and 30% in 2013 and 2014, respectively. Of the 466 registered veterinary surgeons, 147 (31.5%) had been vaccinated, with 72 (15.5%) currently vaccinated. For veterinary students the rabies vaccination rate was 20.0% (4/20) and 13.0% (6/46) in the 2013 and 2014 surveys, respectively. More than 95% of veterinary students had received the mandatory Q fever vaccine. Both veterinarians and students regarded bats and horses as high-risk species for zoonoses. Queensland veterinarians and veterinary students have low levels of protection against ABLV. Although incidents of ABLV spilling over from a bat to a domestic mammal are likely to remain rare, they pose a significant human health and occupational risk given the outcome of infection in humans is high consequence. Principals of veterinary practices and veterinary authorities in Australia should implement a policy of rabies vaccination for clinical staff and veterinary students. © 2018 Australian Veterinary Association.

Childhood vaccination coverage rates among military dependents in the United States.

PubMed

Dunn, Angela C; Black, Carla L; Arnold, John; Brodine, Stephanie; Waalen, Jill; Binkin, Nancy

2015-05-01

The Military Health System provides universal coverage of all recommended childhood vaccinations. Few studies have examined the effect that being insured by the Military Health System has on childhood vaccination coverage. The purpose of this study was to compare the coverage of the universally recommended vaccines among military dependents versus other insured and uninsured children using a nationwide sample of children. The National Immunization Survey is a multistage, random-digit dialing survey designed to measure vaccination coverage estimates of US children aged 19 to 35 months old. Data from 2007 through 2012 were combined to permit comparison of vaccination coverage among military dependent and all other children. Among military dependents, 28.0% of children aged 19 to 35 months were not up to date on the 4:3:1:3:3:1 vaccination series excluding Haemophilus influenzae type b vaccine compared with 21.1% of all other children (odds ratio: 1.4; 95% confidence interval: 1.2-1.6). After controlling for sociodemographic characteristics, compared with all other US children, military dependent children were more likely to be incompletely vaccinated (odds ratio: 1.3; 95% confidence interval: 1.1-1.5). Lower vaccination coverage rates among US military dependent children might be due to this population being highly mobile. However, the lack of a military-wide childhood immunization registry and incomplete documentation of vaccinations could contribute to the lower vaccination coverage rates seen in this study. These results suggest the need for further investigation to evaluate vaccination coverage of children with complete ascertainment of vaccination history, and if lower immunization rates are verified, assessment of reasons for lower vaccination coverage rates among military dependent children. Copyright © 2015 by the American Academy of Pediatrics.

A Multifaceted Approach to RSV Vaccination.

PubMed

Blanco, Jorge C G; Boukhvalova, Marina S; Morrison, Trudy G; Vogel, Stefanie N

2018-05-17

Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. In addition, RSV infections occur throughout different ages, thus, maintaining the virus in circulation, and increasing health risk to more susceptible populations such as infants, the elderly, and the immunocompromised. To date, there is no vaccine approved to prevent RSV infection or minimize symptoms of infection. Current clinical trials for vaccines against RSV are being carried out in four very different populations. There are vaccines that target two different pediatric populations, infants 2 to 6 month of age and seropositive children over 6 months of age, as well as women (non-pregnant or pregnant in their third trimester). There are vaccines that target adult and elderly populations. In this review, we will present and discuss RSV vaccine candidates currently in clinical trials. We will describe the preclinical studies instrumental for their advancement, with the goal of introducing new preclinical models that may more accurately predict the outcome of clinical vaccine studies.

Safe use of vaccines and vaccine compliance with food safety requirements.

PubMed

Grein, K; Papadopoulos, O; Tollis, M

2007-08-01

Advanced technologies and regulatory regimes have contributed to the availability of veterinary vaccines that have high quality and favourable safety profiles in terms of potential risks posed to the target animals, the persons who come into contact with the vaccine, the consumers of food derived from vaccinated animals and the environment. The authorisation process requires that a range of safety studies are provided to evaluate the products. The design and production of vaccines, and their safe use, are primarily assessed by using data gathered from extensive pre-marketing studies performed on target animals and specific quality tests. The current post-marketing safeguards include good manufacturing practices, batch safety testing, inspections and pharmacovigilance. In addition to hazard identification, a full benefit/risk evaluation needs to be undertaken. The outcome of that evaluation will determine options for risk management and affect regulatory decisions on the safety of the vaccine; options might, for example, include special warnings on package inserts and labels.

Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From Synthetic PRR Agonists to the Potential of Defective Interfering Particles of Viruses

PubMed Central

Vasou, Andri; Sultanoglu, Nazife; Goodbourn, Stephen

2017-01-01

Modern vaccinology has increasingly focused on non-living vaccines, which are more stable than live-attenuated vaccines but often show limited immunogenicity. Immunostimulatory substances, known as adjuvants, are traditionally used to increase the magnitude of protective adaptive immunity in response to a pathogen-associated antigen. Recently developed adjuvants often include substances that stimulate pattern recognition receptors (PRRs), essential components of innate immunity required for the activation of antigen-presenting cells (APCs), which serve as a bridge between innate and adaptive immunity. Nearly all PRRs are potential targets for adjuvants. Given the recent success of toll-like receptor (TLR) agonists in vaccine development, molecules with similar, but additional, immunostimulatory activity, such as defective interfering particles (DIPs) of viruses, represent attractive candidates for vaccine adjuvants. This review outlines some of the recent advances in vaccine development related to the use of TLR agonists, summarizes the current knowledge regarding DIP immunogenicity, and discusses the potential applications of DIPs in vaccine adjuvantation. PMID:28703784

Heterologous vaccine effects.

PubMed

Saadatian-Elahi, Mitra; Aaby, Peter; Shann, Frank; Netea, Mihai G; Levy, Ofer; Louis, Jacques; Picot, Valentina; Greenberg, Michael; Warren, William

2016-07-25

The heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological studies and are increasingly recognized as an important biological process by a growing group of immunologists and epidemiologists. Much remain to be learned about the extent and underlying mechanisms for these effects. The conference "Off-target effects of vaccination" held in Annecy-France (June 8-10 2015) intended to take a holistic approach drawing from the fields of immunology, systems biology, epidemiology, bioinformatics, public health and regulatory science to address fundamental questions of immunological mechanisms, as well as translational questions about vaccines NSEs. NSE observations were examined using case-studies on live attenuated vaccines and non-live vaccines followed by discussion of studies of possible biological mechanisms. Some possible pathways forward in the study of vaccines NSE were identified and discussed by the expert group. Copyright © 2016.

Sperm fibrous sheath proteins: a potential new class of target antigens for use in human therapeutic cancer vaccines

PubMed Central

Chiriva-Internati, Maurizio; Cobos, Everardo; Da Silva, Diane M.

2008-01-01

Cancer vaccines have been demonstrated to be a promising strategy for treating human neoplastic disease, but one of the limitations of these vaccines remains the paucity of target antigens to which to direct an effective immune response. We hypothesize that sperm fibrous sheath proteins may be a new class of useful antigens for developing successful cancer vaccines. This hypothesis is supported by the expression of two sperm fibrous sheath proteins, called sperm protein 17 and calcium-binding tyrosine-phosphorylation regulated protein, in tumors of unrelated histological origin and their capability to induce T cell-based immune responses. PMID:18433090

Challenges of assessing the clinical efficacy of asexual blood-stage Plasmodium falciparum malaria vaccines.

PubMed

Sheehy, Susanne H; Douglas, Alexander D; Draper, Simon J

2013-09-01

In the absence of any highly effective vaccine candidate against Plasmodium falciparum malaria, it remains imperative for the field to pursue all avenues that may lead to the successful development of such a formulation. The development of a subunit vaccine targeting the asexual blood-stage of Plasmodium falciparum malaria infection has proven particularly challenging with only limited success to date in clinical trials. However, only a fraction of potential blood-stage vaccine antigens have been evaluated as targets, and a number of new promising candidate antigen formulations and delivery platforms are approaching clinical development. It is therefore essential that reliable and sensitive methods of detecting, or ruling out, even modest efficacy of blood-stage vaccines in small clinical trials be established. In this article we evaluate the challenges facing blood-stage vaccine developers, assess the appropriateness and limitations of various in vivo approaches for efficacy assessment and suggest future directions for the field.

A forecast of typhoid conjugate vaccine introduction and demand in typhoid endemic low- and middle-income countries to support vaccine introduction policy and decisions.

PubMed

Mogasale, Vittal; Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok

2017-09-02

A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy.

A forecast of typhoid conjugate vaccine introduction and demand in typhoid endemic low- and middle-income countries to support vaccine introduction policy and decisions

PubMed Central

Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok

2017-01-01

ABSTRACT A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy. PMID:28604164

Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects

PubMed Central

Buckee, Caroline O.

2018-01-01

Background Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations? Methods and findings We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage. We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts. As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended “Mass and Maintain” strategy. We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover. Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016. Conclusions Oral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility. Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies. PMID:29489815

Immunisation strategies for viral diseases in developing countries.

PubMed

Ruff, T A

1999-01-01

In just under a quarter of a century, the Expanded Programme on Immunisation has been associated with an increase in infant immunisation coverage from around 5% to 80%, and the prevention of at least 3 million deaths annually, at very low cost. The global target of poliomyelitis eradication by the year 2000 appears feasible. Measles is the next likely target for eradication via immunisation, through 'catch-up', 'keep up' and 'follow-up' strategies which have proven highly effective in the Americas. Yet much needs to be done in order to extend readily achievable immunisation benefits equitably to all the world's people and to realise the potential of existing and soon to be available vaccines for disease control and eradication, as experience with yellow fever and hepatitis B vaccines demonstrates. Unsafe injection practices are widespread, have received inadequate attention, and cause a substantial global burden of blood-borne infections. The risk of increasing global inequity in immunisation highlights the centrality of resource allocation priorities in determining the extent to which the benefits of immunisation will be realised, particularly for new vaccines which are significantly more costly than established EPI vaccines. WHO/UNICEF strategies to target more effectively immunisation support to the neediest countries, to prioritise new vaccines, and to target carefully vaccine procurement and encourage sharply tiered vaccine pricing support both equity and sustainability. However, increasing the resources available to immunisation is vital and requires powerful advocacy on public health, moral, cost-effectiveness and legal grounds. More appropriate resource allocation priorities could readily provide the means necessary to address both technical and operational immunisation challenges.

Expanding the recommendations for annual influenza vaccination to school-age children in the United States.

PubMed

Fiore, Anthony E; Epperson, Scott; Perrotta, Dennis; Bernstein, Henry; Neuzil, Kathleen

2012-03-01

Despite long-standing recommendations to vaccinate children who have underlying chronic medical conditions or who are contacts of high-risk persons, vaccination coverage among school-age children remains low. Community studies have indicated that school-age children have the highest incidence of influenza and are an important source of amplifying and sustaining community transmission that affects all age groups. A consultation to discuss the advantages and disadvantages of a universal recommendation for annual influenza vaccination of all children age ≥6 months was held in Atlanta, Georgia, in September 2007. Consultants provided summaries of current data on vaccine effectiveness, safety, supply, successful program implementation, and economics studies and discussed challenges associated with continuing a risk- and contact-based vaccination strategy compared with a universal vaccination recommendation. Consultants noted that school-age children had a substantial illness burden caused by influenza, that vaccine was safe and effective for children aged 6 months through 18 years, and that evidence suggested that vaccinating school-age children would provide benefits to both the vaccinated children and their unvaccinated household and community contacts. However, implementation of an annual recommendation for all school-age children would pose major challenges to parents, medical providers and health care systems. Alternative vaccination venues were needed, and of these school-located vaccination programs might offer the most promise as an alternative vaccination site for school-age children. Expansion of recommendations to include all school-age children will require additional development of an infrastructure to support implementation and methods to adequately evaluate impact.

Seasonal influenza vaccine dose distribution in 157 countries (2004-2011).

PubMed

Palache, Abraham; Oriol-Mathieu, Valerie; Abelin, Atika; Music, Tamara

2014-11-12

Globally there are an estimated 3-5 million cases of severe influenza illness every year, resulting in 250,000-500,000 deaths. At the World Health Assembly in 2003, World Health Organization (WHO) resolved to increase influenza vaccine coverage rates (VCR) for high-risk groups, particularly focusing on at least 75% of the elderly by 2010. But systematic worldwide data have not been available to assist public health authorities to monitor vaccine uptake and review progress toward vaccination coverage targets. In 2008, the International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply task force (IFPMA IVS) developed a survey methodology to assess global influenza vaccine dose distribution. The current survey results represent 2011 data and demonstrate the evolution of the absolute number distributed between 2004 and 2011 inclusive, and the evolution in the per capita doses distributed in 2008-2011. Global distribution of IFPMA IVS member doses increased approximately 86.9% between 2004 and 2011, but only approximately 12.1% between 2008 and 2011. The WHO's regions in Eastern Mediterranean (EMRO), Southeast Asian (SEARO) and Africa (AFRO) together account for about 47% of the global population, but only 3.7% of all IFPMA IVS doses distributed. While distributed doses have globally increased, they have decreased in EURO and EMRO since 2009. Dose distribution can provide a reasonable proxy of vaccine utilization. Based on the dose distribution, we conclude that seasonal influenza VCR in many countries remains well below the WHA's VCR targets and below the recommendations of the Council of the European Union in EURO. Inter- and intra-regional disparities in dose distribution trends call into question the impact of current vaccine recommendations at achieving coverage targets. Additional policy measures, particularly those that influence patients adherence to vaccination programs, such as reimbursement, healthcare provider knowledge, attitudes, practices, and communications, are required for VCR targets to be met and benefit public health. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

PubMed

Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe

2014-02-12

Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international guidelines. Health care managers and policy-makers may consider the strategic potential of utilizing clinical and administrative databases for creating population-specific risk prediction models to inform vaccination campaigns. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigating the Use of an Enterotropic Newcastle Disease Virus as a Recombinant Vaccine Platform Targeting Poultry Enteric Viruses

USDA-ARS?s Scientific Manuscript database

Control strategies for poultry viral enteric disease must include vaccine platforms that have been specifically designed to improve flock performance, lessen disease severity, and reduce viral transmission. With the exception of certain autogenous vaccines, no vaccines currently exist to aid in the ...

Vaccine Pipeline Has Grown During The Past Two Decades With More Early-Stage Trials From Small And Medium-Size Companies.

PubMed

Hwang, Thomas J; Kesselheim, Aaron S

2016-02-01

Many serious diseases lack safe and effective vaccines. Using a large commercial database, we examined trends in global vaccine research and development and found that the proportion of new vaccine candidates entering all stages of clinical development increased by 3-5 percentage points over the past two decades. Small and medium-size companies accounted for nearly twice as many new Phase I vaccine trials compared to large companies, but late-stage (Phase III) vaccine trials were dominated by large companies. There were no significant differences between vaccines and drugs in the probability of success in clinical trials or in profitability. Small and medium-size companies, including spin-outs from academic research centers, play an important role in innovative research and discovery. Our findings suggest that policy making targeted at smaller companies, such as prizes or opportunities for public-private partnerships, could support the development of new vaccines, particularly those targeting unmet medical needs and emerging public health threats. Project HOPE—The People-to-People Health Foundation, Inc.

[Epidemiology of viral hepatitis].

PubMed

Kaić, Bernard; Vilibić-Cavlek, Tatjana; Filipović, Sanja Kurecić; Nemeth-Blazić, Tatjana; Pem-Novosel, Iva; Vucina, Vesna Visekruna; Simunović, Aleksandar; Zajec, Martina; Radić, Ivan; Pavlić, Jasmina; Glamocanin, Marica; Gjenero-Margan, Ira

2013-10-01

Understanding the country-specific epidemiology of disease, which may vary greatly among countries, is crucial for identifying the most appropriate preventive and control measures. An overview of the local epidemiology of viral hepatitis in Croatia is given in this paper. The overall prevalence of hepatitis B in Croatia is low (less than 2% HBsAg carriers in the general population). Hepatitis B incidence and prevalence began to decline significantly following the introduction of universal hepatitis B vaccination in 1999. Information on HBsAg seroprevalence is derived from routine testing of certain subpopulations (pregnant women, blood donors) and seroprevalence studies mostly targeted at high-risk populations. Universal childhood vaccination against hepatitis B remains the main preventive measure. We recommend testing for immunity one to two months after the third dose of hepatitis B vaccine for health-care workers. The incidence and prevalence of hepatitis C have also been declining in the general population. The main preventive measures are ensuring safety of blood products, prevention of drug abuse, and harm reduction programs for intravenous drug users. Hepatitis A incidence has declined dramatically since fifty years ago, when thousands of cases were reported annually. In the last five years, an average of twenty cases have been reported per year. The reduction of hepatitis A is a consequence of improved personal and community hygiene and sanitation. Hepatitis D has not been reported in Croatia. The risk of hepatitis D will get to be even smaller as the proportion of population vaccinated against hepatitis B builds up. Hepatitis E is reported only sporadically in Croatia, mostly in persons occupationally in contact with pigs and in travelers to endemic countries. In conclusion, Croatia is a low prevalence country for hepatitides A, B and C. Hepatitis D has not been reported to occur in Croatia and there are only sporadic cases of hepatitis E. Since hepatitis A is a rare disease occurring sporadically, which is a consequence of improved sanitation and hygiene, hepatitides B and C are the main causes of viral hepatitis in Croatia. The introduction of universal mandatory hepatitis B vaccination of schoolchildren in 1999 resulted in a decrease in the incidence of hepatitis B, which is most pronounced in adolescents and young adults, and further decrease in the incidence and prevalence is expected as the pool of susceptible individuals decreases through vaccination. The incidence of hepatitis C is decreasing as well. In spite of a relatively favorable epidemiological situation, hepatitis B and C are still a significant public health burden with an estimated 25,000 persons chronically infected with HBV and about 40,000 persons chronically infected with HCV in Croatia.

Prevention of the spread of rabies to wildlife by oral vaccination of raccoons in Massachusetts.

PubMed

Robbins, A H; Borden, M D; Windmiller, B S; Niezgoda, M; Marcus, L C; O'Brien, S M; Kreindel, S M; McGuill, M W; DeMaria, A; Rupprecht, C E; Rowell, S

1998-11-15

To evaluate the use of bait containing rabies vaccine to create a barrier of rabies-vaccinated raccoons in Massachusetts and to determine the effectiveness of various bait distribution strategies in halting the spread of rabies. Prospective study. Free-ranging raccoons. Baits were distributed twice yearly in a 207-km2 (80-mi2) area in the vicinity of the Cape Cod Canal. Bait density and distribution strategy varied among 3 treatment areas. Raccoons were caught in live traps after bait distribution and anesthetized; blood samples were obtained to measure serum antibody titers to rabies virus. Vaccination rates were determined by the percentage of captured raccoons with antibody titers to rabies virus > or = 1:5. In addition, raccoons with clinical signs of illness inside the vaccination zone and adjacent areas were euthanatized and submitted for rabies testing. The percentage of vaccinated raccoons differed significantly among the following 3 areas with various bait densities: high-density area with uniform bait distribution (103 baits/km2 [267 baits/mi2]) = 37%; low-density area with additional targeted bait distribution (93 baits/km2 [240 baits/mi2]) = 67%; and, high-density area with additional targeted bait distribution (135 baits/km2 [350 baits/mi2]) = 77%. Nineteen animals with rabies (15 raccoons, 3 skunks, 1 cat) were reported in the area just outside of the vaccination zone, but only 1 raccoon with rabies was reported from inside the vaccination zone. In this suburban study area, an approximate vaccination rate of 63% was sufficient to halt the spread of rabies in free-ranging raccoons. Compared with uniform bait distribution, targeting raccoon habitats increased vaccination rates.

Evaluating Vaccination Strategies for Zika Virus in the Americas.

PubMed

Durham, David P; Fitzpatrick, Meagan C; Ndeffo-Mbah, Martial L; Parpia, Alyssa S; Michael, Nelson L; Galvani, Alison P

2018-05-01

Mosquito-borne and sexually transmitted Zika virus has become widespread across Central and South America and the Caribbean. Many Zika vaccine candidates are under active development. To quantify the effect of Zika vaccine prioritization of females aged 9 to 49 years, followed by males aged 9 to 49 years, on incidence of prenatal Zika infections. A compartmental model of Zika transmission between mosquitoes and humans was developed and calibrated to empirical estimates of country-specific mosquito density. Mosquitoes were stratified into susceptible, exposed, and infected groups; humans were stratified into susceptible, exposed, infected, recovered, and vaccinated groups. Age-specific fertility rates, Zika sexual transmission, and country-specific demographics were incorporated. 34 countries and territories in the Americas with documented Zika outbreaks. Males and females aged 9 to 49 years. Age- and sex-targeted immunization using a Zika vaccine with 75% efficacy. Annual prenatal Zika infections. For a base-case vaccine efficacy of 75% and vaccination coverage of 90%, immunizing females aged 9 to 49 years (the World Health Organization target population) would reduce the incidence of prenatal infections by at least 94%, depending on the country-specific Zika attack rate. In regions where an outbreak is not expected for at least 10 years, vaccination of women aged 15 to 29 years is more efficient than that of women aged 30 years or older. Population-level modeling may not capture all local and neighborhood-level heterogeneity in mosquito abundance or Zika incidence. A Zika vaccine of moderate to high efficacy may virtually eliminate prenatal infections through a combination of direct protection and transmission reduction. Efficiency of age-specific targeting of Zika vaccination depends on the timing of future outbreaks. National Institutes of Health.

Using the COMMVAC taxonomy to map vaccination communication interventions in Mozambique

PubMed Central

Muloliwa, Artur Manuel; Cliff, Julie; Oku, Afiong; Oyo-Ita, Angela; Glenton, Claire; Ames, Heather; Kaufman, Jessica; Hill, Sophie; Cartier, Yuri; Bosch-Capblanch, Xavier; Rada, Gabriel; Lewin, Simon

2017-01-01

ABSTRACT Background: Improved communication about childhood vaccination is fundamental to increasing vaccine uptake in low-income countries. Mozambique, with 64% of children fully vaccinated, uses a range of communication interventions to promote uptake of childhood immunisation. Objectives: Using a taxonomy developed by the ‘Communicate to Vaccinate’ (COMMVAC) project, the study aims to identify and classify the existing communication interventions for vaccination in Mozambique and to find the gaps. Methods: We used a qualitative research approach to identify the range of communication interventions used in Mozambique. In-depth semi-structured interviews were carried out with key purposively selected personnel at national level and relevant documents were collected and analysed. These data were complemented with observations of communication during routine vaccination and campaigns in Nampula province. We used the COMMVAC taxonomy, which organises vaccination communication intervention according to its intended purpose and the population targeted, to map both routine and campaign interventions. Results: We identified interventions used in campaign and routine vaccination, or in both, fitting five of the seven taxonomy purposes, with informing or educating community members predominating. We did not identify any interventions that aimed to provide support or facilitate decision-making. There were interventions for all main target groups, although fewer for health providers. Overlap occurred: for example, interventions often targeted both parents and community members. Conclusions: We consider that the predominant focus on informing and educating community members is appropriate in the Mozambican context, where there is a high level of illiteracy and poor knowledge of the reasons for vaccination. We recommend increasing interventions for health providers, in particular training them in better communication for vaccination. The taxonomy was useful for identifying gaps, but needs to be more user-friendly if it is to be employed as a tool by health service managers. PMID:28573937

[From new vaccine to new target: revisiting influenza vaccination].

PubMed

Gérard, M

2011-09-01

Annual vaccination is since many years the corner stone of Influenza control strategy. Because conventional vaccine are needle-based, are less immunogenic in old people and induce only systemic IgG production, intranasal and intradermal vaccines that are recently or will be soon available in Belgium will offer distinct advantages. Intradermal vaccination is on the Belgian market since 2010. A stronger immune response that allows an antigen sparing strategy is elicited because antigens are delivered near the dermal dendritic cells. Local side effects are more pronounced than after intramuscular injection. The needle-free intranasal vaccine that has been approved for use in people less than 18 years old by the EMEA in October 2010 induces also a mucosal IgA response. Improved clinical results than with intramuscular vaccine has been documented in several studies in children. Several conditions are contraindication to nasal vaccination because of patterns of side effects and because the vaccine is an live-attenuated vaccine. Pregnant women has become a top priority for Influenza vaccination in the recommendations of the High Council of Health in Belgium since the 2009 H1N1 pandemic. Several studies has since then documented the increased risk for Influenza-related morbidity in pregnant women especially during the third trimester and independently of the presence of other comorbidities. Reduced incidence of documented Influenza and of Influenza-related hospitalizations are observed in the new born of vaccinated women until 6 months of age. Availability of new vaccines for Influenza and better knowledge of the benefit of vaccination in target populations are important tools to optimize vaccine coverage of the population.

Plasmodium immunomics.

PubMed

Doolan, Denise L

2011-01-01

The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ∼5300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing <0.5% of the genome. The recent availability of comprehensive genomic, proteomic and transcriptomic datasets from human and selected non-human primate and rodent malarias provide a foundation to exploit for vaccine development. This information can be mined to identify promising vaccine candidate antigens, by proteome-wide screening of antibody and T cell reactivity using specimens from individuals exposed to malaria and technology platforms such as protein arrays, high throughput protein production and epitope prediction algorithms. Such antigens could be incorporated into a rational vaccine development process that targets specific stages of the Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritising antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed. Copyright © 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Evaluation of lamb and calf responses to Rift Valley fever MP-12 vaccination.

PubMed

Wilson, William C; Bawa, Bhupinder; Drolet, Barbara S; Lehiy, Chris; Faburay, Bonto; Jasperson, Dane C; Reister, Lindsey; Gaudreault, Natasha N; Carlson, Jolene; Ma, Wenjun; Morozov, Igor; McVey, D Scott; Richt, Jürgen A

2014-08-06

Rift Valley fever (RVF) is an important viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. The disease is of concern to international agricultural and public health communities. The RVFV MP-12 strain has been the most safety tested attenuated vaccine strain; thus it is being considered as a potential vaccine for the US national veterinary stockpile. This study was designed to establish safety protocols for large animal research with virulent RVF viruses, establish a target host immune response baseline using RVF MP-12 strain, and independently evaluate this strain as a potential US emergency response vaccine. Ten, approximately four month-old lambs and calves were vaccinated with RVF MP-12 strain; two additional animals per species provided negative control specimens. The animals were monitored for clinical and immune response, fever, and viremia. Two animals per species were sacrificed on 2, 3, 4, 10 and 28 days post infection and full necropsies were performed for histopathological examination. No clinical or febrile responses were observed in this study. The onset and titer of the immune response is discussed. There was no significant histopathology in the lambs; however, 6 out of 10 vaccinated calves had multifocal, random areas of hepatocellular degeneration and necrosis. RVF MP12 antigen was detected in these areas of necrosis by immunohistochemistry in one calf. This study provides independent and baseline information on the RVF MP-12 attenuated vaccination in vaccine relevant age target species and indicates the importance of performing safety testing on vaccine relevant aged target animals. Published by Elsevier B.V.

A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells.

PubMed

Glaffig, Markus; Stergiou, Natascha; Hartmann, Sebastian; Schmitt, Edgar; Kunz, Horst

2018-01-08

A MUC1 anticancer vaccine equipped with covalently linked divalent mannose ligands was found to improve the antigen uptake and presentation by targeting mannose-receptor-positive macrophages and dendritic cells. It induced much stronger specific IgG immune responses in mice than the non-mannosylated reference vaccine. Mannose coupling also led to increased numbers of macrophages, dendritic cells, and CD4 + T cells in the local lymph organs. Comparison of di- and tetravalent mannose ligands revealed an increased binding of the tetravalent version, suggesting that higher valency improves binding to the mannose receptor. The mannose-coupled vaccine and the non-mannosylated reference vaccine induced IgG antibodies that exhibited similar binding to human breast tumor cells. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

PubMed Central

Kataoka, Kosuke; Fujihashi, Kohtaro

2009-01-01

In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens. PMID:19722892

Safety of live vaccines on immunosuppressive or immunomodulatory therapy-a retrospective study in three Swiss Travel Clinics.

PubMed

Huber, Fabienne; Ehrensperger, Benoît; Hatz, Christoph; Chappuis, François; Bühler, Silja; Eperon, Gilles

2018-01-01

Patients increasingly benefit from immunosuppressive/immunomodulatory medications for a range of conditions allowing them a lifestyle similar to healthy individuals, including travel. However, the administration of live vaccines to immunodeficient patients bears the risk of replication of the attenuated vaccine microorganism. Therefore, live vaccines are generally contraindicated on immunosuppression. Data on live vaccinations on immunosuppressive/immunomodulatory medication are scarce. We identified all travellers seeking pre-travel advice in three Swiss travel clinics with a live vaccine during immunosuppressive/immunomodulatory therapy to ascertain experienced side effects. A retrospective and multi-centre study design was chosen to increase the sample size. This study was conducted in the travel clinics of the University of Zurich; the Swiss TPH, Basel; and Geneva University Hospitals. Travellers on immunosuppressive/immunomodulatory therapy who received live vaccines [yellow fever vaccination (YFV), measles/mumps/rubella (MMR), varicella and/ or oral typhoid vaccination (OTV)] between 2008 and 2015 were identified and interviewed. A total of 60 age- and sex-matched controls (matched to Basel/Zurich travel clinics travellers) were included. Overall, 197 patients were identified. And 116 patients (59%) and 60 controls were interviewed. YFV was administered 92 times, MMR 21 times, varicella 4 times and OTV 6 times to patients on immunosuppressive/immunomodulatory therapy. Most common medications were corticosteroids (n = 45), mesalazine (n = 28) and methotrexate (n = 19). Live vaccines were also administered on biological treatment, e.g. TNF-alpha inhibitors (n = 8). Systemic reactions were observed in 12.2% of the immunosuppressed vs 13.3% of controls; local reactions in 7.8% of the immunosuppressed vs 11.7% of controls. In controls, all reactions were mild/moderate. In the immunosuppressed, 2/21 severe reactions occurred: severe local pain on interferon-beta and severe muscle/joint pain on sulfasalazine. Safety of live vaccines given to immunosuppressed patients cannot be concluded. However, it is re-assuring that in the examined patient groups no serious side effects or infections by the attenuated vaccine strain occurred. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Mumps vaccine performance among university students during a mumps outbreak.

PubMed

Cortese, Margaret M; Jordan, Hannah T; Curns, Aaron T; Quinlan, Patricia A; Ens, Kim A; Denning, Patricia M; Dayan, Gustavo H

2008-04-15

The largest reported mumps outbreak at a US college in 19 years occurred in 2006 at a Kansas university with a 2-dose measles-mumps-rubella (MMR) vaccination policy. We assessed vaccine performance and mumps risk factors, including the possibility of waning vaccine protection. Case students were compared with a cohort of the university's approximately 19,000 undergraduates. The secondary attack rate for clinical mumps was determined among roommates exposed to case students. Time from receipt of the second dose of MMR vaccine was compared between case students and roommates without mumps. Coverage with > or =2 dose of MMR vaccine was > or =95% among 140 undergraduate case students and 444 cohort students. The secondary attack rate for clinical mumps among roommates who had received 2 doses of vaccine ranged from 2.2% to 7.7%, depending on the case definition. Compared with roommates without mumps, case students were more likely (odds ratio, 2.46; 95% confidence interval, 1.25-4.82) to have received their second dose of MMR vaccine > or =10 years earlier. The odds of being a case student increased with each 1-year increase in time from receipt of the second dose of MMR vaccine (odds ratio, 1.36; 95% confidence interval, 1.10-1.68) among case students and roommates aged 18-19 years but not among those aged > or =20 years. Students aged 18-19 years had a higher risk of mumps (risk ratio, 3.14; 95% confidence interval, 1.60-6.16), compared with students aged > or =22 years; women living in dormitories had increased risk of mumps (risk ratio, 1.95; 95% confidence interval, 1.01-3.76), compared with men not living in dormitories. High 2-dose MMR coverage protected many students from developing mumps but was not sufficient to prevent the mumps outbreak. Vaccine-induced protection may wane. Similar US settings where large numbers of young adults from wild-type naive cohorts live closely together may be at particular risk for mumps outbreaks.

Do Pneumococcal Conjugate Vaccines Represent Good Value for Money in a Lower-Middle Income Country? A Cost-Utility Analysis in the Philippines.

PubMed

Haasis, Manuel Alexander; Ceria, Joyce Anne; Kulpeng, Wantanee; Teerawattananon, Yot; Alejandria, Marissa

2015-01-01

The objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies. A cost-utility analysis was conducted. A Markov simulation model was constructed to examine the costs and consequences of PCV10 and PCV13 against the current scenario of no PCV vaccination for a lifetime horizon. A health system perspective was employed to explore different funding schemes, which include universal or partial vaccination coverage subsidized by the government. Results were presented as incremental cost-effectiveness ratios (ICERs) in Philippine peso (Php) per QALY gained (1 USD = 44.20 Php). Probabilistic sensitivity analysis was performed to determine the impact of parameter uncertainty. With universal vaccination at a cost per dose of Php 624 for PCV10 and Php 700 for PCV13, both PCVs are cost-effective compared to no vaccination given the ceiling threshold of Php 120,000 per QALY gained, yielding ICERs of Php 68,182 and Php 54,510 for PCV10 and PCV13, respectively. Partial vaccination of 25% of the birth cohort resulted in significantly higher ICER values (Php 112,640 for PCV10 and Php 84,654 for PCV13) due to loss of herd protection. The budget impact analysis reveals that universal vaccination would cost Php 3.87 billion to 4.34 billion per annual, or 1.6 to 1.8 times the budget of the current national vaccination program. The inclusion of PCV in the national immunization program is recommended. PCV13 achieved better value for money compared to PCV10. However, the affordability and sustainability of PCV implementation over the long-term should be considered by decision makers.

Cost effectiveness of a pentavalent rotavirus vaccine in Oman.

PubMed

Al Awaidy, Salah Thabit; Gebremeskel, Berhanu G; Al Obeidani, Idris; Al Baqlani, Said; Haddadin, Wisam; O'Brien, Megan A

2014-06-17

Rotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in Oman A Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives. A universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective. Universal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective.

Cost effectiveness of a pentavalent rotavirus vaccine in Oman

PubMed Central

2014-01-01

Background Rotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in Oman Methods A Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives. Results A universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective. Conclusions Universal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective. PMID:24941946

Routine vaccination against chickenpox?

PubMed

2012-04-01

Varicella-zoster virus (VZV) causes both varicella and herpes zoster. In 1995 a varicella vaccine was licensed in the USA and was incorporated into the routine vaccination programme for children; a decline of varicella among children and adults, and a reduction in associated hospitalisation, complications and mortality, has resulted. In the UK, a policy of targeted vaccination of at-risk groups has been in place since the vaccine was introduced. Here we review the evidence for the different approaches to VZV vaccination policy.

Feasibility of a Catch-Up HPV Vaccination Program among College Students Attending a Large Rural University in the South

ERIC Educational Resources Information Center

Richman, Alice R.; Haithcox-Dennis, Melissa J.; Allsbrook, Ashley R.

2012-01-01

Our study explored the eligibility and willingness of students to participate in a university-wide catch-up Human papillomavirus (HPV) vaccination program. A total of 1804 electronic surveys (82% response) assessing demographics, HPV knowledge, eligibility, and willingness were gathered. HPV knowledge was moderate, with just over a quarter (26%)…

A Qualitative Analysis of Factors Influencing HPV Vaccine Uptake in Soweto, South Africa among Adolescents and Their Caregivers

PubMed Central

Katz, Ingrid T.; Nkala, Busisiwe; Dietrich, Janan; Wallace, Melissa; Bekker, Linda-Gail; Pollenz, Kathryn; Bogart, Laura M.; Wright, Alexi A.; Tsai, Alexander C.; Bangsberg, David R.; Gray, Glenda E.

2013-01-01

Background In South Africa, the prevalence of oncogenic Human Papillomavirus (HPV) may be as high as 64%, and cervical cancer is the leading cause of cancer-related death among women. The development of efficacious prophylactic vaccines has provided an opportunity for primary prevention. Given the importance of psycho-social forces in vaccine uptake, we sought to elucidate factors influencing HPV vaccination among a sample of low-income South African adolescents receiving the vaccine for the first time in Soweto. Methods The HPV vaccine was introduced to adolescents in low-income townships throughout South Africa as part of a nationwide trial to understand adolescent involvement in future vaccine research targeting human immunodeficiency virus (HIV). We performed in-depth semi-structured interviews with purposively-sampled adolescents and their care providers to understand what forces shaped HPV vaccine uptake. Interviews were recorded, transcribed, translated, and examined using thematic analysis. Results Of 224 adolescents recruited, 201 initiated the vaccine; 192 (95.5%) received a second immunization; and 164 (81.6%) completed three doses. In our qualitative study of 39 adolescent-caregiver dyads, we found that factors driving vaccine uptake reflected a socio-cultural backdrop of high HIV endemnicity, sexual violence, poverty, and an abundance of female-headed households. Adolescents exercised a high level of autonomy and often initiated decision-making. Healthcare providers and peers provided support and guidance that was absent at home. The impact of the HIV epidemic on decision-making was substantial, leading participants to mistakenly conflate HPV and HIV. Conclusions In a setting of perceived rampant sexual violence and epidemic levels of HIV, adolescents and caregivers sought to decrease harm by seeking a vaccine targeting a sexually transmitted infection (STI). Despite careful consenting, there was confusion regarding the vaccine’s target. Future interventions promoting STI vaccines will need to provide substantial information for participants, particularly adolescents who may exercise a significant level of autonomy in decision-making. PMID:24023613

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

NASA Astrophysics Data System (ADS)

Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

School-Located Influenza Vaccination Clinics: Local Health Department Perspectives

ERIC Educational Resources Information Center

Ransom, James

2009-01-01

Universal childhood influenza vaccination presents challenges and opportunities for health care and public health systems to vaccinate the children who fall under the new recommendation. Advisory Committee on Immunization Practices (ACIP) recommendations and guidelines are helpful, but they do not provide strategies on how to deliver immunization…

Human Papillomavirus Vaccine Intent and Uptake among Female College Students

ERIC Educational Resources Information Center

Patel, Divya A.; Zochowski, Melissa; Peterman, Stephanie; Dempsey, Amanda F.; Ernst, Susan; Dalton, Vanessa K.

2012-01-01

Objective: To examine human papillomavirus (HPV) vaccine intent and the effect of an educational intervention on vaccine uptake among female college students. Participants: Females aged 18 to 26 attending a university health service gynecology clinic (n = 256). Methods: Participants were randomized to receive either HPV-specific education with a…

Female students receiving post-secondary education in Greece: the results of a collaborative human papillomavirus knowledge survey.

PubMed

Michail, G; Smaili, M; Vozikis, A; Jelastopulu, E; Adonakis, G; Poulas, K

2014-12-01

Contrary to the optimistic forecasts, existing until 2008 and despite the incorporation of the vaccine into the Greek National Immunization Program, six years later, the percentage of HPV vaccination coverage in Greece remains disappointingly low. The aim of this extended study was to investigate the knowledge, behaviour and attitude of a representative sample of the initial target group; young female students of Greek higher education institutions to Pap cervical screening, biology of HPV infection and principles of HPV vaccination. Cross-sectional study. One thousand two hundred ten (1210) questionnaires were completed by young female students aged 17-24 years. The survey questionnaire sought data relating to sociodemographic characteristics, health behaviour and knowledge about HPV, as well as vaccination status. 79.6% of the sample reported at least one annual gynaecologic examination and 92.6% were familiar with the rationale of cervical screening; however only 52.9% had undergone a Pap smear. 69.7% reported adequate knowledge about HPV and 89.3% were aware of the possible course of HPV infection. Despite most (95.9%) were aware of vaccine availability, vaccinated students represented only 33.1%. According to the multivariate analysis, vaccination status was associated with university studies (OR 1.96; 95% CI: 1.19-3.20), parental area of expertise (OR 2.77; 95% CI: 1.18-6.53, OR 2.03; 95% CI: 1.05-3.94), and adequate knowledge of the reasons for which women should undergo regular cervical screening (OR 4.23; 85% CI: 1.55-11.55). Fear of side-effects and equivocal information were the main reasons of non-vaccination (52.2% and 33.1% respectively). Finally, the majority of unvaccinated individuals showed a positive attitude towards prospective HPV vaccination, providing they received well-documented advising. Young women attending Greek higher education exhibit a good level of knowledge about HPV and its correlation with cervical cancer. These data highlight the need for further sensitization of the general population. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Enhancement of Cancer Vaccine Therapy by Systemic Delivery of a Tumor Targeting Salmonella-based STAT3 shRNA Suppresses the Growth of Established Melanoma Tumors

PubMed Central

Manuel, Edwin R.; Blache, Céline A.; Paquette, Rebecca; Kaltcheva, Teodora I.; Ishizaki, Hidenobu; Ellenhorn, Joshua D.I.; Hensel, Michael; Metelitsa, Leonid; Diamond, Don J.

2011-01-01

Cancer vaccine therapies have only achieved limited success when focusing on effector immunity with the goal of eliciting robust tumor-specific T cell responses. More recently, there is an emerging understanding that effective immunity can only be achieved by coordinate disruption of tumor-derived immune suppression. Towards that goal, we have developed a potent Salmonella-based vaccine expressing codon-optimized survivin (CO-SVN) referred to as 3342Max. When used alone as a therapeutic vaccine, 3342Max can attenuate growth of aggressive murine melanomas overexpressing SVN. However, under more immunosuppressive conditions, such as those associated with larger tumor volumes, we found that the vaccine was ineffective. Vaccine efficacy could be rescued if tumor-bearing mice were treated initially with Salmonella encoding a shRNA targeting the tolerogenic molecule STAT3 (YS1646-shSTAT3). In vaccinated mice, silencing STAT3 increased the proliferation and granzyme B levels of intratumoral CD4+ and CD8+ T cells. The combined strategy also increased apoptosis in tumors of treated mice, enhancing tumor-specific killing of tumor targets. Interestingly, mice treated with YS1646-shSTAT3 or 3342Max alone were similarly unsuccessful in rejecting established tumors, while the combined regimen was highly potent. Our findings establish that a combined strategy of silencing immunosuppressive molecules followed by vaccination can act synergistically to attenuate tumor growth, and they offer a novel translational direction to improve tumor immunotherapy. PMID:21527558