Iskander, John; Haber, Penina; Herrera, Guillermo
In the event that a vaccine is available during an influenza pandemic, vaccine safety monitoring will occur as part of comprehensive public health surveillance of the vaccination campaign. Though inactivated influenza vaccines have been widely used in the United States and much is known about their safety profile, attention will need to be paid to both common self-limited adverse reactions and rarer, more serious events that may or may not be causally related to vaccination. The primary surveillance systems used to generate and test hypotheses about vaccine safety concerns are the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD), respectively. Examples of recent use of these systems to investigate influenza vaccine safety and enhancements planned for use during a pandemic are presented. Ethical issues that will need to be addressed as part of an overall vaccine safety response include risk communication and injury compensation. Advance planning and the use of available technologic solutions are needed to respond to the scientific and logistic challenges involved in safely implementing mass vaccination during a pandemic. PMID:17132333
Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A
Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children.
... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...
Gotoh, Kensei; Ito, Yoshinori; Suzuki, Eitaro; Kaneko, Kenitiro; Kiuchi, Tetsuya; Ando, Hisami; Kimura, Hiroshi
Annual influenza vaccination is recommended for pediatric liver transplant recipients, who are at high risk of influenza-related complications. However, effectiveness and safety of vaccination may differ among influenza seasons in this population and have not been fully evaluated. Subjects comprised 38 pediatric liver transplant recipients with or without influenza vaccination through the 2006-2007, 2007-2008 and 2008-2009 influenza seasons. Recipients received inactivated trivalent (AH1/AH3/B) influenza vaccine, and comparisons were made to non-vaccinated recipients with regard to effectiveness and safety. No significant differences were seen between recipient groups for acute allograft rejection, acute febrile illness, or influenza virus infection. No serious systemic adverse events were observed in vaccinated recipients. Seroprotection rate (defined as the proportion of recipients with HI antibody titer ≥ 1:40), seroconversion rate (proportion of recipients with a ≥ 4-fold increase in HI titers), and geometric mean titers were mostly elevated after vaccination for the three influenza antigens in each season. These three indicators of immunogenicity showed similar results in both vaccinated recipients and vaccinated healthy children in the 2007-2008 season. These findings suggest that pediatric liver transplant patients may respond safely to inactivated seasonal influenza vaccines in a similar manner to healthy children, and effectiveness varies among influenza seasons.
Swayne, D E; Suarez, D L
Until recently, most vaccines against avian influenza were based on oil-emulsified inactivated low- or high-pathogenicity viruses. Now, recombinant fowl pox and avian paramyxovirus type 1 vaccines with avian influenza H5 gene inserts (+ or - N1 gene insert) are available and licensed. New technologies might overcome existing limitations to make available vaccines that can be grown in tissue culture systems for more rapid production; provide optimized protection, as a result of closer genetic relations to field viruses; allow mass administration by aerosol, in drinking-water or in ovo; and allow easier strategies for identifying infected birds within vaccinated populations (DIVA). The technologies include avian influenza viruses with partial gene deletions, avian influenza-Newcastle disease virus chimeras, vectored vaccines such as adenoviruses and Marek's disease virus, and subunit vaccines. These new methods should be licensed only after their purity, safety, efficacy and potency against avian influenza viruses have been demonstrated, and, for live vectored vaccines, restriction of viral transmission to unvaccinated birds. Use of vaccines in countries affected by highly pathogenic avian influenza will not only protect poultry but will provide additional safety for consumers. Experimental studies have shown that birds vaccinated against avian influenza have no virus in meat and minimal amounts in eggs after HPAI virus challenge, and that replication and shedding from their respiratory and alimentary tracts is greatly reduced.
Parrella, Adriana; Gold, Michael; Marshall, Helen; Braunack-Mayer, Annette; Watson, Maureen; Baghurst, Peter
To assess parental vaccine safety views and future vaccination decisions after an adverse event following immunization (AEFI) experienced by their child. A cross-sectional telephone survey was conducted of parents of children aged 0-7 y, identified in AEFI reports submitted to the South Australian Immunization Section, Department Health. The reports included childhood National Immunization Program (NIP), seasonal or pandemic influenza vaccines. Interviews were conducted following a national suspension of the 2010 seasonal trivalent influenza (STIV) vaccine. Parental attitudes toward vaccine safety, reasons for reporting the AEFI and impact on future vaccination intent were assessed. Of 179 parents interviewed, 88% were confident in the safety of vaccines in general. Parents reporting an AEFI to the STIV were more likely to state the event had influenced future vaccination decisions than the NIP vaccine reporters (65% vs 14%, p < 0.001), with 63% stating refusal or hesitance to re-vaccinate their children against influenza. Media reports of the 2010 STIV program suspension was the most common reason for reporting an AEFI for parents of children who received an influenza vaccination. The AEFI experience did not impact on parental decision to continue with routine childhood NIP schedules, regardless of whether children received influenza or NIP vaccines. In contrast, most parents whose child experienced an AEFI to the 2010 STIV stated decreased confidence in the safety of influenza vaccines, which is likely to have impacted on the uptake of seasonal influenza vaccination in 2011. Addressing influenza vaccine safety concerns to promote influenza vaccination in the community is required.
The squalene oil-in-water emulsion MF-59 adjuvant was developed initially to enhance the immunogenicity of influenza vaccines in populations such as children and adults with known suboptimal response. Developed in the 1990s, it was initially licensed in Europe for use in seasonal influenza vaccine in the elderly. Since that time, both Avian and p2009H1N1 vaccines have also been developed. Overall, more than 30,000 individuals have participated in clinical trials of MF-59 adjuvanted vaccine and more than 160 million doses of licensed vaccine have been administered. Safety and effectiveness data from clinical trials and observation studies attest to the safety of MF-59 and to its ability to enhance the effectiveness of influenza vaccines in children and the elderly.
Lone, Nazir I; Kavanagh, Kimberley; Robertson, Chris; McMenamin, Jim; von Wissmann, Beatrix; Vasileiou, Eleftheria; Butler, Chris; Ritchie, Lewis D; Gunson, Rory; Schwarze, Jürgen; Sheikh, Aziz
Introduction Seasonal (inactivated) influenza vaccination is recommended for all individuals aged 65+ and in individuals under 65 who are at an increased risk of complications of influenza infection, for example, people with asthma. Live attenuated influenza vaccine (LAIV) was recommended for children as they are thought to be responsible for much of the transmission of influenza to the populations at risk of serious complications from influenza. A phased roll-out of the LAIV pilot programme began in 2013/2014. There is limited evidence for vaccine effectiveness (VE) in the populations targeted for influenza vaccination. The aim of this study is to examine the safety and effectiveness of the live attenuated seasonal influenza vaccine programme in children and the inactivated seasonal influenza vaccination programme among different age and at-risk groups of people. Methods and analysis Test negative and cohort study designs will be used to estimate VE. A primary care database covering 1.25 million people in Scotland for the period 2000/2001 to 2015/2016 will be linked to the Scottish Immunisation Recall Service (SIRS), Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. Vaccination status (including LAIV uptake) will be determined from the primary care and SIRS database. The primary outcome will be influenza-positive real-time PCR tests carried out in sentinel general practices and other healthcare settings. Secondary outcomes include influenza-like illness and asthma-related general practice consultations, hospitalisations and death. An instrumental variable analysis will be carried out to account for confounding. Self-controlled study designs will be used to estimate the risk of adverse events associated with influenza vaccination. Ethics and dissemination We obtained approval from the National Research Ethics Service Committee, West Midlands—Edgbaston. The study findings will be presented at
Fiore, Anthony E; Bridges, Carolyn B; Cox, Nancy J
safety of LAIV among young children suggest an increased risk of wheezing in some young children, and the vaccine is not recommended for children younger than 2 years old, ages 2-4 old with a history of recurrent wheezing or reactive airways disease, or older persons who have any medical condition that confers an increased risk of influenza-related complications.The effectiveness of influenza vaccines is related predominantly to the age and immune competence of the vaccinee and the antigenic relatedness of vaccine strains to circulating strains. Vaccine effectiveness in preventing laboratory-confirmed influenza illness when the vaccine strains are well matched to circulating strains is 70-90% in randomized, placebo-controlled trials conducted among children and young healthy adults, but is lower among elderly or immunocompromised persons. In years with a suboptimal match, vaccine benefit is likely to be lower, although the vaccine can still provide substantial benefit, especially against more severe outcomes. Live, attenuated influenza vaccines have been most extensively studied among children, and have been shown to be more effective than inactivated vaccines in several randomized controlled trials among young children.Influenza vaccination is recommended in the United States for all children six months or older, all adults 50 years or older, all persons with chronic medical conditions, and pregnant women, and contacts of these persons, including healthcare workers. The global disease burden of influenza is substantial, and the World Health Organization has indicated that member states should evaluate the cost-effectiveness of introducing influenza vaccination into national immunization programs. More research is needed to develop more effective seasonal influenza vaccines that provide long-lasting immunity and broad protection against strains that differ antigenically from vaccine viruses.
Vasil'eva, R I; Merkur'eva, L A; Iatsenko, V G; Vasil'eva, A M; Shvager, M M
In a strictly controlled epidemiological trial on 12,643 school children aged 11-14 years the reactogenic properties and safety of killed influenza chromatographic vaccine under the conditions of multiple immunization were studied. A single immunization dose of the vaccine (0.2 ml) contained the hemagglutinins of influenza viruses A/Philippines/82 (H3N3) and A/Kiev/59/79 (H1N1), 3.5 micrograms each. The preparation was introduced by means of a jet injector. The vaccine was shown to be clinically and immunologically safe under the conditions of the regular multiple immunization of children over the period of 4 years.
Jacobson, Robert M
Rates of reported adverse events are remarkably low. VAERS identifies an adverse event rate approximating 11.4 reports per 100,000 vaccine doses. Approximately 15% of these reports represent SAEs, but less than 2% involve death; in most cases, reviews have shown no causal relation between the events and the vaccine. Across the spectrum of vaccines in use (including those directed against influenza and hepatitis B virus), many claims of adverse events regarding vaccines represent typical reactions to vaccinations. These reactions can be thought of as foreign-body reactions and predominate among the inactivated vaccines. In controlled studies, the adverse event rates that occur with vaccination resemble those that occur with placebo injections. Typical reactions associated with live viral and bacterial vaccines, such as MMR and varicella vaccines, may resemble attenuated forms of the disease for which the vaccine is directed. Other claims against vaccines represent chance-coincidence or misunderstood data; further studies of claims have vindicated the overall safety of the vaccines in most cases. Two documented safety concerns with vaccines, however, have demonstrated that vaccines (like other biologics and pharmacologic) can result in harm (eg, rotavirus and OPV vaccines). The denouement with these vaccines indicates the broad postmarketing data collection and evaluation that extends efforts made with prelicensure study to balance the benefits from vaccination with the risk for harm. Overall, measures including prelicensure study and postlicensure surveillance, such as VAERS, the Vaccine Safety Datalink Project, and the Clinical Immunization Safety Assessment Centers, have resulted in an exceptional safety profile for the vaccines in use.
Beeler, Judy A; Eichelberger, Maryna C
Respiratory viral infections in infants and young children frequently cause illness that can easily progress to hospitalization and death. There are currently no licensed vaccines to prevent respiratory viral disease in children younger than 6 months, reflecting safety concerns and the difficulty in inducing effective immune responses in infants. This review discusses vaccines that have been developed, or are currently being developed, against influenza and respiratory syncytial virus, with a focus on studies performed to demonstrate their safety and efficacy, and the impact of immunologic immaturity and maternal antibodies on the infant response to vaccines.
... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.
Heinrichs, D; Sennekamp, J; Kirsten, A; Kirsten, D
Allergic alveolitis as a side effect of vaccination is very rare. We report a life-threatening complication in a female patient after influenza vaccination. The causative antigen was the influenza virus itself. Our Patient has suffered from exogen-allergic alveolitis for 12 years. Because of the guidelines of regular administration of influenza vaccination in patients with chronic pulmonary disease further research in patients with known exogen-allergic alveolitis is vitally important for the pharmaceutical drug safety.
Naleway, Allison L; Irving, Stephanie A; Henninger, Michelle L; Li, De-Kun; Shifflett, Pat; Ball, Sarah; Williams, Jennifer L; Cragan, Janet; Gee, Julianne; Thompson, Mark G
Pregnant women and their infants are vulnerable to severe disease and secondary complications from influenza infection. For this reason, annual influenza vaccination is recommended for all pregnant women in the United States. Women frequently cite concerns about vaccine safety as a barrier to vaccination. This review describes the safety of inactivated influenza vaccination during pregnancy with a focus on maternal obstetric events, including hypertensive disorders, gestational diabetes, and chorioamnionitis. Included in the review are new findings from two studies which examined the safety of seasonal inactivated influenza vaccination during pregnancy. The first study enrolled 641 pregnant women during the 2010-2011 season and prospectively followed them until delivery or pregnancy termination. The second study enrolled 1616 pregnant women during the 2010-2011 influenza season, and followed the women and their infants for six months after delivery. No associations between inactivated influenza vaccination and gestational diabetes, gestational hypertension, preeclampsia/eclampsia, or chorioamnionitis were observed in either cohort. When considered as a whole, these studies should further reassure women and clinicians that influenza vaccination during pregnancy is safe for mothers.
Hwang, Kao-Pin; Hsu, Yu-Lung; Hsieh, Tsung-Hsueh; Lin, Hsiao-Chuan; Yen, Ting-Yu; Wei, Hsiu-Mei; Lin, Hung-Chih; Chen, An-Chyi; Chow, Julie Chi; Huang, Li-Min
This prospective study aimed to investigate the immune responses and safety of an influenza vaccine in vaccine-naïve infants aged 6-12 months, and was conducted from November 2010 to May 2011. Fifty-nine infants aged 6-12 months received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Hemagglutination inhibition titers were measured 4 weeks after the two doses of study vaccine. Based on the assumption that a hemagglutination inhibition titer of 1:40 or greater against the antigen would be protective in adults, two doses of the study vaccine generated a protective immune response of 63.2% against influenza A(H1N1), 82.5% against influenza A(H3N2) and 38.6% against influenza B viruses in infants aged 6-12 months. The geometric mean fold rises against influenza type A and B viruses also met the European Medicines Agency criteria for flu vaccines. The solicited events within 7 days after vaccination were mild in intensity. No deaths or adverse events such as optic neuritis, cranial neuropathy, and brachial neuropathy or Guillain-Barre syndrome were reported. Two doses of inactivated influenza vaccine were well tolerated and induced a protective immune response against influenza in infants aged 6-12 months.
Piedra, Pedro A
The trivalent, cold-adapted influenza vaccine (CAIV-T, FluMist, Aviron, Mountain View, CA) is a live attenuated influenza virus vaccine that is administered by nasal spray. CAIV-T is efficacious in preventing influenza virus infection. The vaccine was submitted to the Food and Drug Administration for licensure in healthy children and adults. Universal immunization is being considered in children, and an effective vaccine with minimal adverse reactions is thus required. The published studies on the safety of CAIV-T in children reviewed in this article were clinical trials sponsored by the National Institutes of Health (NIH) conducted in children from 1975 to 1991, clinical trials from 1991 to 1993 sponsored by a cooperative agreement between NIH and Wyeth-Ayerst Research, and clinical trials from 1995 to the present sponsored by a cooperative agreement between NIH and Aviron. Safety assessments included the occurrence of: 1) specific influenza-like symptoms, unexpected symptoms, and use of medications within the first 10 days after vaccination; 2) acute illness and use of medication within 11 to 42 days postvaccination; 3) serious adverse events and rare events within 42 days after vaccination; 4) healthcare utilization within 14 days after vaccination; and 5) acute respiratory symptoms with annual sequential vaccine doses. CAIV-T was safe and well-tolerated. Transient, mild respiratory symptoms were observed in a minority (10%-15%) of children and primarily with the first CAIV-T dose. Vomiting and abdominal pain occurred in fewer than 2 percent of CAIV-T recipients. The gastrointestinal symptoms were mild and of short duration. An excess of illness or use of medication was not observed after the 10th day of vaccination. Sequential annual doses of CAIV-T were well-tolerated and not associated with increased reactogenicity. CAIV-T did not cause an increase in healthcare utilization. Thus CAIV-T is safe in healthy children and should complement the use of inactivated
Song, Hyoyoung; Bock, Hans; Guadagno, Alana; Costantini, Marco; Baehner, Frank; Kim, Yeon Ho; Ahn, Seung In; Son, Ki Hyuk; Yim, Dong-Seok
Haemophilus influenzae type b (Hib) is a major cause of meningitis and pneumonia with high morbidity and mortality rates in young children. The introduction of effective and well-tolerated conjugate Hib vaccines, has nearly eradicated this disease in many countries. We investigated the safety of the Hib PRP-CRM197 vaccine in a multi-center post-marketing surveillance (PMS) study. Korean children (N = 764) aged 1-33 months were enrolled when receiving a routine primary immunization or a booster vaccine with Hib PRP-CRM197 and solicited and unsolicited adverse events (AEs) were recorded using a diary card for 7 and 28 days after each vaccination, respectively. In this study, AEs were reported by 66% of subjects but were generally mild, with 42% of subjects reporting solicited AEs and 46% reporting unsolicited AEs. Among the unsolicited AEs, 98% were determined to be unrelated to the study vaccine. The studied Hib PRP-CRM197 vaccine was well tolerated by the study group and found to have a similar safety profile to that reported in other clinical studies. This vaccine is suitable for routine immunization against Hib disease among Korean children. AEs due to this vaccine will continue to be monitored.
Naval Health Research Center Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant Women and Their Newborns Ava M.S. Conlin Anna...Safety of the Pandemic H1N1 Influenza Vaccine Among Pregnant U.S. Military Women and Their Newborns Ava Marie S. Conlin, DO, MPH, Anna T. Bukowinski...active-duty U.S. military women who received pandemic H1N1 vaccine during pregnancy as well as adverse health outcomes among the newborns resulting from
Ambrose, Christopher S.; Levin, Myron J.
Two antigenically distinct lineages of influenza B viruses have circulated globally since 1985. However, licensed trivalent seasonal influenza vaccines contain antigens from only a single influenza B virus and thus provide limited immunity against circulating influenza B strains of the lineage not present in the vaccine. In recent years, predictions about which B lineage will predominate in an upcoming influenza season have been no better than chance alone, correct in only 5 of the 10 seasons from 2001 to 2011. Consequently, seasonal influenza vaccines could be improved by inclusion of influenza B strains of both lineages. The resulting quadrivalent influenza vaccines would allow influenza vaccination campaigns to respond more effectively to current global influenza epidemiology. Manufacturing capacity for seasonal influenza vaccines has increased sufficiently to supply quadrivalent influenza vaccines, and methods to identify the influenza B strains to include in such vaccines are in place. Multiple manufacturers have initiated clinical studies of quadrivalent influenza vaccines. Data from those studies, taken together with epidemiologic data regarding the burden of disease caused by influenza B infections, will determine the safety, effectiveness, and benefit of utilizing quadrivalent vaccines for the prevention of seasonal influenza disease. PMID:22252006
Bae, E Young; Choi, Ui Yoon; Kwon, Hyo Jin; Jeong, Dae Chul; Rhim, Jung Woo; Ma, Sang Hyuk; Lee, Kyung Il; Kang, Jin Han
Influenza virus vaccination is recommended for children, but so far, active vaccination has not been achieved because most parents lack knowledge of vaccine safety and many doctors are reluctant to administer vaccine due to concerns that steroids might alter immunogenicity. The aim of this study was to compare the immunogenicity and safety of inactivated trivalent split influenza virus vaccine between children with recurrent wheezing and healthy children of the same age group. Sixty-eight healthy children and 62 children with recurrent wheezing took part in this study. Seroconversion rates, seroprotection rates, geometric mean titers (GMTs), and geometric mean titer ratios (GMTRs) were measured by a hemagglutination inhibition assay for the assessment of immunogenicity. Solicited and unsolicited local and systemic adverse events were measured for the assessment of safety. Regarding immunogenicity, the seroconversion and seroprotection rates showed no difference overall between healthy children and children with recurrent wheezing. Also, no difference was observed between steroid-treated and nontreated groups with recurrent wheezing. Generally, the GMTs after vaccination were higher in the one-dose vaccination groups for healthy children and children with recurrent wheezing, but the GMTRs revealed different results according to strain in the two groups. Regarding safety, solicited local and systemic adverse events showed no differences between healthy children and children with recurrent wheezing. This study demonstrates that inactivated split influenza virus vaccine is able to induce protective immune responses in healthy children, as observed in previous studies, as well as in children with recurrent wheezing who require frequent steroid treatment.
Liao, Zhengfa; Tang, Hao; Xu, Xiaojia; Liang, Yaping; Xiong, Yongzhen; Ni, Jindong
Objective To assess the immunogenicity and safety of influenza vaccine in patients with systemic lupus erythematosus (SLE). Methods Relevant articles were retrieved from electronic databases. Seroprotection rate, seroconversion rate and factors that increase antibody geometric mean titer (GMT) were used as indices to measure the immunogenicity. The safety of vaccine was assessed through monitoring adverse events, which included side effects and SLE exacerbations. We performed a meta-analysis of influenza vaccine seroprotection, seroconversion and adverse effects. SLE exacerbation after vaccination was comprehensively described. We used the Committee for Proprietary Medicinal Products (CPMP) guidelines to determine whether influenza can induce adequate immunogenicity in patients with SLE. Results Eighteen studies with 1966 subjects met the inclusion criteria. At least 565 of the subjects were patients with low-to-moderate SLE Disease Activity Index (SLEDAI) score or stable SLE disease. Compared with the general population, seroprotection rate in SLE patients was significantly decreased in patients with H1N1 [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.27–0.50] and H3N2 vaccination (OR = 0.48, 95% CI: 0.24–0.93), but not influenza B vaccination (OR = 0.55, 95% CI: 0.24–1.25). Seroconversion rate also significantly decreased in patients with H1N1 (OR = 0.39, 95% CI: 0.27–0.57) and influenza B (OR = 0.47, 95% CI: 0.29–0.76) vaccination, but not H3N2 vaccination (OR = 0.62, 95% CI: 0.21–1.79). However, the immunogenicity of influenza vaccine in SLE patients almost reached that of the CPMP guidelines. The OR for side effects (patients versus healthy controls) was 3.24 (95% CI: 0.62–16.76). Among 1966 patients with SLE, 32 experienced mild exacerbation of SLE and five had serious side effects for other reasons. Conclusion Influenza vaccine has moderate effect on protecting patients with SLE. The side effects of influenza vaccine are not serious
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Sarsenbayeva, Gulbanu; Volgin, Yevgeniy; Kassenov, Markhabbat; Issagulov, Timur; Bogdanov, Nikolay; Nurpeissova, Ainur; Sagymbay, Altynay; Abitay, Ruslan; Stukova, Marina; Sansyzbay, Abylay; Khairullin, Berik
The paper describes the results of preclinical testing of the preparation 'Vaccine allantoic split-virus inactivated against seasonal influenza'. Acute toxicity and local irritating effect, anaphylactic reactions to different antigens (vaccine and ovalbumin), delayed-type hypersensitivity to ram erythrocytes, humoral immune response in hemaggtination reaction, immunogenic activity was studied in laboratory animals of various species (mice, rats, guinea pigs). Comparative analysis of the results from testing immunogenic activity of the preparation under study and the commercial influenza vaccines was performed. The preclinical testing has demonstrated safety and immune response of the seasonal split influenza vaccine, so it may be recommended for clinical study on limited contingent of volunteers. This article is protected by copyright. All rights reserved.
Esposito, Susanna; Giavoli, Claudia; Trombetta, Claudia; Bianchini, Sonia; Montinaro, Valentina; Spada, Anna; Montomoli, Emanuele; Principi, Nicola
Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p<0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p<0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p<0.01 for GMT values and p<0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile.
Nishi, Junichiro; Tokuda, Koichi; Imuta, Naoko; Minami, Taketsugu; Kawano, Yoshifumi
Haemophilus influenzae type b (Hib) conjugate vaccine (PRP-T) and heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in December 2008 and February 2010, respectively. The concurrent administration of these vaccines is routinely performed worldwide. However, the safety of the simultaneous administration of these vaccines has not been fully evaluated in Japan, because it has rarely been performed thus far. We conducted a 2-year prospective, observational, multicenter study on PRP-T and PCV7 safety from February 2009 through January 2011 in 29 facilities located in Kagoshima Prefecture, Japan. Objective severe adverse events included anaphylactoid reaction, encephalitis/encephalopathy, neurological events, severe focal reactions, systemic eruption/urticaria, fever above 39℃ within 2 days after inoculation, and other complications requiring hospitalization. The incidences of these events for PRP-T and PCV7 administration were 0.68% (76/11,197) and 0.92% (28/3,049), respectively. No deaths or subsequent complications were reported during the course of the study. There was no significant difference in the incidence of severe adverse events between the single and co-administration groups for both vaccines: PRP-T, 0.55% (31/5,662) versus 0.81% (45/5,535; P = 0.11); PCV7, 0.88% (11/1,247) versus 0.94% (17/1,802; P = 0.86). These results suggest that the simultaneous administration of vaccines including PRP-T and/or PCV7 does not increase the incidence of severe adverse events in Japanese children.
Comparison of immunogenicity and safety of an influenza vaccine administered concomitantly with a 13-valent pneumococcal conjugate vaccine or 23-valent polysaccharide pneumococcal vaccine in the elderly
Purpose Previous studies have demonstrated the immunogenicity and safety of the co-administration of the trivalent inactivated influenza vaccine (IIV3) with the polysaccharide pneumococcal vaccine (PPV) or pneumococcal conjugate vaccine (PCV). However, there is no direct comparison study that evaluates the immunogenicity and safety of IIV3 given concomitantly with PCV13 or PPV23 in the elderly. Materials and Methods During the 2012-2013 influenza vaccination period, 224 healthy elderly volunteers aged 65 years and older randomly received IIV3 given concomitantly with either PCV13 (PCV13+IIV3) or PPV23 (PPV23+IIV3) in a 1:1 ratio. Serum hemagglutination-inhibiting antibodies for IIV3 were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded prospectively in a clinical diary during a 7-day period. Results A total of 220 participants blood samples for analysis of immunogenicity and kept a clinical diary for safety analysis (PCV13+IIV3, n=110; PPV23+IIV3, n=110). One month after vaccination, both groups satisfied the Committee for Medical Products for Human Use criteria for A/H1N1, A/H3N2 and B strains, showing comparable seroprotection rates, seroconversion rates and geometric mean titer fold. The assessments of immunogenicity were similar in both groups. The most common local and systemic reactions were pain at the injection site and generalized myalgia. They were generally mild or moderate in intensity. The adverse events were not statistically different between the two groups. Conclusion PCV13+IIV3 and PPV23+IIV3 demonstrated similar immunogenicity and safety in the elderly. PMID:28168172
Lécu, Alexis; De Langhe, Christophe; Petit, Thierry; Bernard, Frédéric; Swam, Hanny
Due to the spread of the H5N1 highly pathogenic strain of avian influenza virus across Europe, a preventive vaccination occurred in early 2006 among 135 French zoologic institutions. Approximately 25,000 birds were vaccinated with a H5N2 inactivated vaccine. Among them, 4,369 birds were monitored by members of Association Francophone des Vétérinaires de Parc Zoologique regarding safety issues of the vaccination protocol. A total of 1,686 blood samples were collected before the first injection (n = 255), at the time of booster (n = 463), 60 day after the booster (n = 514), and 180 day (n = 229) and 330 day (n = 217) after the initial injection. Thus, sera of 126 species representing 15 different avian orders were tested using the hemagglutinin inhibition assay to evaluate seroconversion and the long-term serologic profile of selected anti-H5 antibody. Safety was considered satisfactory in all orders, and there were no deleterious effects on large-volume injection/body weight ratio. After the second injection, 71% of the birds developed a titer > or =32, with a mean titer of 558. Titers then decreased in all birds, with 42% of the remaining birds having a titer > or =32 at day 180 and only 26% at day 330. Results demonstrated that a booster 42 days after initial vaccination was mandatory to raise the titer above 32, considered to be the protective level in poultry, and to increase the number of seroconverted birds. Differences in the serologic responses among the orders and species of birds were detected and could be linked with the variation of vaccine dose injected per body weight or with species-specific immune response. The protocol for additional campaigns will be adjusted for some bird orders through the increase of injected dose or a half yearly booster to sustain better titers over the year. Vaccination is a useful tool, together with biosecurity, that should always be used as a primary method of preventing and controlling avian influenza outbreaks.
La Torre, Giuseppe; Mannocci, Alice; Colamesta, Vittoria; D’Egidio, Valeria; Sestili, Cristina; Spadea, Antonietta
Background The risk of getting influenza and pneumococcal disease is higher in cancer patients, and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To assess flu and pneumococcal vaccinations efficacy, effectiveness, and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in the scientific literature about the flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 22 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI=6–62%) for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI=23.2 – 63.3 %) and 39.6 % (95% CI=26%–54.1%) for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI=19.7–51.2%) for H1N1, 23% (95% CI=16.6–31.5%) for H3N2, 29% (95% CI=21.3–37%) for B. Conclusion Despite the low rate of response, flu, and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines. PMID:27648207
Yin, J Kevin; Khandaker, Gulam; Rashid, Harunor; Heron, Leon; Ridda, Iman; Booy, Robert
The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta-analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta-analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta-analysis, covering 17,921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non-adjuvanted vaccine). Non-adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination-associated adverse events were reported, both of which resolved fully. No death or case of Guillain-Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6-35 months) may need to receive two doses of non-adjuvanted vaccine or one dose of AS03(A/B)-adjuvanted product to achieve seroprotection.
Houser, Katherine; Subbarao, Kanta
Vaccination is the best method for the prevention and control of influenza. Vaccination can reduce illness and lessen severity of infection. This review focuses on how currently licensed influenza vaccines are generated in the U.S., why the biology of influenza poses vaccine challenges, and vaccine approaches on the horizon that address these challenges. PMID:25766291
Yin, J. Kevin; Khandaker, Gulam; Rashid, Harunor; Heron, Leon; Ridda, Iman; Booy, Robert
Please cite this paper as: Yin et al. (2011) Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta‐analysis. Influenza and Other Respiratory Viruses 5(5), 299–305. The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta‐analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta‐analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta‐analysis, covering 17 921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non‐adjuvanted vaccine). Non‐adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination‐associated adverse events were reported, both of which resolved fully. No death or case of Guillain–Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6–35 months) may need to receive two
Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin
In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.
van Doorn, Eva; Liu, Heng; Ben-Yedidia, Tamar; Hassin, Shimon; Visontai, Ildiko; Norley, Stephen; Frijlink, Henderik W.; Hak, Eelko
Abstract Introduction: Influenza is a major respiratory viral infection of humans with high mortality and morbidity rates and profound economic impact. Although influenza vaccines are generally updated yearly to match the viruses expected in the coming season, genetic mutation and reassortment can result in unexpected novel strains. Therefore, it is important to develop universal vaccines inducing protective immunity to such strains before they appear. This clinical trial is designed to evaluate the safety and immunogenicity of Multimeric-001 (M-001), which contains conserved epitopes of influenza A and B. M-001 is able to induce both humoral and cellular immunity and provides broad strain coverage. Methods: In a multicenter, randomized, double-blind, and controlled phase IIb trial, 222 healthy volunteers aged 18 to 60 years will be randomized into 3 groups (1:1:1) to receive either 2 intramuscular injections of 0.5 mg M-001 (arm 1), 1.0 mg M-001 (arm 2), or saline (arm 3—placebo), before receiving an investigational (whole virus, inactivated, aluminum phosphate gel [AlPO4]-adjuvanted) prepandemic influenza vaccine (H5N1). Primary outcomes are safety and cellular immune responses (cell-mediated immunity [CMI]) induced by M-001, evaluated by multiparametric flow cytometry of intracellular cytokines. The secondary outcome is the serum hemagglutination inhibition (HAI) titer toward the H5N1 vaccine strain. Additionally, exploratory outcomes include evaluation of CMI by quantitative reverse transcription polymerase chain reaction of cytokine mRNA, HAI titers toward H5-drifted strains, serum single radial hemolysis titers toward the H5N1 study vaccine, and the association between CMI markers and antibody response. Discussion: There is a need for influenza vaccines that give the population a broader protection against multiple strains of influenza virus. M-001 might be such vaccine which will be tested in this current trial as a standalone vaccine and as a pandemic
Cooper, C L; Davis, H L; Morris, M L; Efler, S M; Krieg, A M; Li, Y; Laframboise, C; Al Adhami, M J; Khaliq, Y; Seguin, I; Cameron, D W
CPG 7909, a 24-mer B-Class CpG oligodeoxynucleotide (ODN), was tested for safety, tolerability and its ability to augment the immunogenicity of a commercial trivalent killed split influenza vaccine (Fluarix containing A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94; SmithKline Beecham) in a phase Ib blinded, randomized, controlled clinical trial. Sixty healthy volunteers were recruited in two consecutive cohorts of 30 subjects, who were randomly assigned to receive Fluarix plus 1mg CPG 7909 or Fluarix plus saline control (15 subjects each). Vaccines were administered by intramuscular injection on a single occasion with subjects in the first cohort receiving a 1/10th dose of Fluarix and those in the second cohort receiving the full-dose. All safety measures including physical evaluation, laboratory blood assays, and assays for DNA autoimmunity were within normal values except for transient and clinically inconsequential decreases in total white blood cell counts in groups receiving CPG 7909. All vaccines were found to be generally well tolerated with similar frequency and intensity for most adverse reactions for groups receiving CPG 7909 as controls. Exceptions were injection site pain and headache, which were reduced in frequency in subjects receiving the 1/10th Fluarix dose without CpG, compared to the frequency in all other groups. There was a lack of pre-existing immunity, defined as hemagglutinin inhibition (HI) activity < or =20, for all subjects to the influenza strains A/Beijing/262/95 and B/Harbin/7/94 and for some subjects to A/Sydney/5/97. Post-vaccination humoral immune responses, as determined 2 and 4 weeks later by assay of HI activity and ELISA to detect antibodies against hemagglutinin (anti-HA) were similar for both full and reduced Fluarix doses but the cellular immune responses (measured as PBMC antigen-specific IFN-gamma secretion) were reduced in the 1/10th Fluarix dose group. Humoral responses were not significantly enhanced by the addition
Taylor, Laura; Greeley, Rebecca; Dinitz-Sklar, Jill; Mazur, Nicole; Swanson, Jill; Wolicki, JoEllen; Perz, Joseph; Tan, Christina; Montana, Barbara
On September 30, 2015, the New Jersey Department of Health (NJDOH) was notified by an out-of-state health services company that an experienced nurse had reused syringes for multiple persons earlier that day. This occurred at an employee influenza vaccination clinic on the premises of a New Jersey business that had contracted with the health services company to provide influenza vaccinations to its employees. The employees were to receive vaccine from manufacturer-prefilled, single-dose syringes. However, the nurse contracted by the health services company brought three multiple-dose vials of vaccine that were intended for another event. The nurse reported using two syringes she found among her supplies to administer vaccine to 67 employees of the New Jersey business. She reported wiping the syringes with alcohol and using a new needle for each of the 67 persons. One of the vaccine recipients witnessed and questioned the syringe reuse, and brought it to the attention of managers at the business who, in turn, reported the practice to the health services company contracted to provide the influenza vaccinations.
Every year, Influenza virus infection is at the origin of substantial excess in morbidity and mortality in developed as well as developing countries. Influenza viruses undergo antigenic drift which cause annual replacement of strain included in classical trivalent vaccines. Less frequently, this virus can also undergo antigenic shift, which corresponds to a major antigenic change and can lead to an extra medical burden. Several vaccines have been made available to immunize individuals against seasonal as well as pandemic influenza viruses. For seasonal Influenza vaccines, live attenuated and classical inactivated trivalent vaccines have been licensed and are widely used. Additionally, several strategies are under investigations to improve further the efficacy of existing seasonal vaccines in children and elderly. These include the use of adjuvant, increase in antigen content, or alternative route of delivery. Similarly, several approaches have been licensed to address additional challenge posed by pandemic viruses. The different vaccination strategies used to maximise protection against seasonal as well as pandemic influenza will be reviewed and discussed in the perspective the current threat posed by the H1N1v pandemic Influenza.
Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael
A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to <18 years of age. Subjects were stratified as follows: Cohort A (≥6 months to <3 years); Cohort B (≥3 years to <9 years); and Cohort C (≥9 years to <18 years). The subject's age and influenza vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts.
Division of Infectious Diseases and Dept of Laboratory Medicine, Boston, MA; eImmunization Safety Office, Division of Healthcare Quality Promotion...Centers for Disease Control and Prevention, Atlanta, GA; fMilitary Vaccine Agency, United States Army, Falls Church, VA; gNational Center for Patient...Department of Defense VAERS—Vaccine Adverse Event Reporting System CDC—Centers for Disease Control and Prevention VSD—Vaccine Safety Datalink RCA—rapid cycle
Imamura, Takashi; Sakamoto, Ryuichi; Sasaki, Takashi; Kokumai, Norihide; Ohgitani, Toshiaki; Sawata, Akira; Lin, Zhifeng; Sakaguchi, Masashi
We previously reported the development of an inactivated oil-adjuvanted avian influenza vaccine using an apathogenic H5N1 strain of the same lineage as the Eurasian lineage viruses currently epidemic in Asia. In this study, we confirmed the safety and evaluated the efficacy of this vaccine in layer chicken farms by field trials. No problematic adverse reactions occurred in the safety test. In addition, no adverse effects were observed in the field trial, and the antibody titer exceeded a protective level (hemagglutination inhibition (HI) antibody titer of 16) at 3 weeks after a single injection. Based on the above findings, this vaccine was confirmed to be safe and induced a protective level of antibody titer with a single injection in the chickens at the farms.
Medlock, Jan; Galvani, Alison P
The criteria to assess public health policies are fundamental to policy optimization. Using a model parametrized with survey-based contact data and mortality data from influenza pandemics, we determined optimal vaccine allocation for five outcome measures: deaths, infections, years of life lost, contingent valuation, and economic costs. We find that optimal vaccination is achieved by prioritization of schoolchildren and adults aged 30 to 39 years. Schoolchildren are most responsible for transmission, and their parents serve as bridges to the rest of the population. Our results indicate that consideration of age-specific transmission dynamics is paramount to the optimal allocation of influenza vaccines. We also found that previous and new recommendations from the U.S. Centers for Disease Control and Prevention both for the novel swine-origin influenza and, particularly, for seasonal influenza, are suboptimal for all outcome measures.
Zhang, Han; El Zowalaty, Mohamed E
Influenza is an illness of global public health concern. Influenza viruses have been responsible for several pandemics affecting humans. Current influenza vaccines have proved satisfactory safety; however, they have limitations and do not provide protection against unexpected emerging influenza virus strains. Therefore, there is an urgent need for alternative approaches to conventional influenza vaccines. The development of universal influenza vaccines will help alleviate the severity of influenza pandemics. Influenza DNA vaccines have been the subject of many studies over the past decades due to their ability to induce broad-based protective immune responses in various animal models. The present review highlights the recent advances in influenza DNA vaccine research and its potential as an affordable universal influenza vaccine.
Ben-Yehuda, Arie; Joseph, Aviva; Barenholz, Yechezkel; Zeira, Evelyne; Even-Chen, Simcha; Louria-Hayon, Igal; Babai, Ilan; Zakay-Rones, Zichria; Greenbaum, Evgenia; Galprin, Ilia; Glück, Reinhard; Zurbriggen, Rinaldo; Kedar, Eli
Influenza and its complications account for substantial morbidity and mortality, especially among the elderly. In young adults, immunization provides 70-90% protection, while among the elderly the vaccine may be only =50% effective; hence, the need for new, more immunogenic vaccines. We compared the safety and immunogenicity of a novel, interleukin-2 (IL-2) -supplemented trivalent liposomal influenza vaccine (designated INFLUSOME-VAC) with that of a commercial trivalent split virion vaccine in community-residing elderly volunteers (mean age 81 years) in winter of 2000/2001. Eighty-one individuals were randomly assigned to be vaccinated intramuscularly, either with the standard vaccine (n=33) or with INFLUSOME-VAC (n=48) prepared from the former. The two vaccines contained equal amounts of hemagglutinin (HA) ( approximately 15 microgram of each viral strain); INFLUSOME-VAC consisted of liposomal antigens admixed with liposomal human IL-2 (Lip IL-2) (33 microgram = 6x10(5) IU/dose). At 1 month post-vaccination, seroconversion rates (tested by hemagglutination inhibition) for the A/New Caledonia (H1N1) and A/Moscow (H3N2) strains were significantly higher (P=0.04) in the INFLUSOME-VAC group (65 versus 45%, 44 versus 24%, respectively). Moreover, INFLUSOME-VAC induced a greater anti-neuraminidase (NA-N2) response (P<0.05). Anti-IL-2 antibodies were undetected, and no increase in anti-phospholipid IgG antibodies was found in the INFLUSOME-VAC group. Adverse reactions were similar in both groups. Thus, INFLUSOME-VAC appears to be both safe and more immunogenic than the currently used vaccine in the elderly.
... die from flu, and many more are hospitalized.Flu vaccine can:keep you from getting flu, make flu ... inactivated or recombinant influenza vaccine?A dose of flu vaccine is recommended every flu season. Children 6 months ...
Greene, Sharon K; Rett, Melisa; Weintraub, Eric S; Li, Lingling; Yin, Ruihua; Amato, Anthony A; Ho, Doreen T; Sheikh, Sarah I; Fireman, Bruce H; Daley, Matthew F; Belongia, Edward A; Jacobsen, Steven J; Baxter, Roger; Lieu, Tracy A; Kulldorff, Martin; Vellozzi, Claudia; Lee, Grace M
An increased risk of Guillain-Barré syndrome (GBS) following administration of the 1976 swine influenza vaccine led to a heightened focus on GBS when monovalent vaccines against a novel influenza A (H1N1) virus of swine origin were introduced in 2009. GBS cases following receipt of monovalent inactivated (MIV) and seasonal trivalent inactivated (TIV) influenza vaccines in the Vaccine Safety Datalink Project in 2009-2010 were identified in electronic data and confirmed by medical record review. Within 1-42 days following vaccination, 9 cases were confirmed in MIV recipients (1.48 million doses), and 8 cases were confirmed in TIV-only recipients who did not also receive MIV during 2009-2010 (1.72 million doses). Five cases following MIV and 1 case following TIV-only had an antecedent respiratory infection, a known GBS risk factor; furthermore, unlike TIV, MIV administration was concurrent with heightened influenza activity. In a self-controlled risk interval analysis comparing GBS onset within 1-42 days following MIV with GBS onset 43-127 days following MIV, the risk difference was 5.0 cases per million doses (95% confidence interval: 0.5, 9.5). No statistically significant increased GBS risk was found within 1-42 days following TIV-only vaccination versus 43-84 days following vaccination (risk difference = 1.1 cases per million doses, 95% confidence interval: -3.1, 5.4). Further evaluation to assess GBS risk following both vaccination and respiratory infection is warranted.
Shaw, Alan R
Influenza vaccines have been available since the 1950s and have seen increasingly wide use as public health authorities expanded recommendations. Recent events including shortages and avian influenza outbreaks have renewed interest in influenza vaccines, particularly improved vaccines.
Mizukami, Takuo; Momose, Haruka; Kuramitsu, Madoka; Takizawa, Kazuya; Araki, Kumiko; Furuhata, Keiko; Ishii, Ken J.; Hamaguchi, Isao; Yamaguchi, Kazunari
Vaccines are beneficial and universal tools to prevent infectious disease. Thus, safety of vaccines is strictly evaluated in the preclinical phase of trials and every vaccine batch must be tested by the National Control Laboratories according to the guidelines published by each country. Despite many vaccine production platforms and methods, animal testing for safety evaluation is unchanged thus far. We recently developed a systems biological approach to vaccine safety evaluation where identification of specific biomarkers in a rat pre-clinical study evaluated the safety of vaccines for pandemic H5N1 influenza including Irf7, Lgals9, Lgalsbp3, Cxcl11, Timp1, Tap2, Psmb9, Psme1, Tapbp, C2, Csf1, Mx2, Zbp1, Ifrd1, Trafd1, Cxcl9, β2m, Npc1, Ngfr and Ifi47. The current study evaluated whether these 20 biomarkers could evaluate the safety, batch-to-batch and manufacturer-to-manufacturer consistency of seasonal trivalent influenza vaccine using a multiplex gene detection system. When we evaluated the influenza HA vaccine (HAv) from four different manufactures, the biomarker analysis correlated to findings from conventional animal use tests, such as abnormal toxicity test. In addition, sensitivity of toxicity detection and differences in HAvs were higher and more accurate than with conventional methods. Despite a slight decrease in body weight caused by HAv from manufacturer B that was not statistically significant, our results suggest that HAv from manufacturer B is significantly different than the other HAvs tested with regard to Lgals3bp, Tapbp, Lgals9, Irf7 and C2 gene expression in rat lungs. Using the biomarkers confirmed in this study, we predicted batch-to-batch consistency and safety of influenza vaccines within 2 days compared with the conventional safety test, which takes longer. These biomarkers will facilitate the future development of new influenza vaccines and provide an opportunity to develop in vitro methods of evaluating batch-to-batch consistency and
Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han
A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.
Aguilar-Díaz, Fatima Del Carmen; Jiménez-Corona, Maria Eugenia; Ponce-de-León-Rosales, Samuel
We undertook this study to review attitudes, beliefs and practices of healthcare workers (HCW) toward pandemic influenza A vaccine (H1N1) 2009 reported in the literature. Relevant papers published from 2009-2011 reporting attitudes, beliefs and practices of HCW towards pandemic influenza vaccine were identified. Variables such as age, gender, profession, work place area, and previous vaccination uptake were analyzed. In this study, 30 articles regarding attitudes and beliefs toward pandemic influenza vaccination, vaccine uptake and intention to accept vaccine were analyzed. Most studies were cross-sectional in design. Vaccination intention and uptake varies among different countries, 13.5-89.0% and 7.5-63.0%, respectively. Most common reasons for rejection were fear of adverse events, doubt regarding efficacy, not feeling as belonging to a high-risk group and believing that influenza is not a serious illness. Physicians show more favorable attitudes compared to nurses. The main predictor of vaccine uptake was having received previous influenza vaccination. Pandemic influenza uptake was low in most countries. The main reason among HCW for rejection was concern regarding side effects. It is necessary to establish educational programs to provided reliable information and raise awareness of HCW about vaccine use so that they can act as vaccine promoters among the general population.
Vaccines against avian influenza (AI) have had more limited use in poultry than vaccines against other poultry diseases such as Newcastle disease (ND) and infectious bronchitis, and have been used more commonly in the developing world. Over the past 40 years, AI vaccines have been primarily based o...
Background Pneumococcal infections are major causes of child mortality and morbidity worldwide and antibiotic resistance of Streptococcus pneumoniae is a major concern, especially in Asian countries. The present study was designed to evaluate the reactogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the licensed diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus and H. influenzae type b vaccine (DTPa-HBV-IPV/Hib) in a 3-dose primary vaccination course in Vietnamese infants. Methods This phase III, open, randomised study was conducted in one centre in Ho Chi Minh City between February and July 2011. Healthy infants (N=300) were randomised (2:1) to receive either PHiD-CV co-administered with DTPa-HBV-IPV/Hib (PHiD-CV group) or DTPa-HBV-IPV/Hib alone (Control group) at 2, 3, and 4 months of age. Results Within 31 days post-vaccination, 8.2% of overall doses in the PHiD-CV group and 3.0% of overall doses in the Control group were followed by at least one solicited and/or unsolicited, local and/or general adverse event of grade 3 intensity. Pain at injection site was the most common grade 3 solicited symptom, which was reported following 6.5% and 1.0% of overall doses in the PHiD-CV and Control groups, respectively. Within 4 days post-vaccination, the most common solicited local and general symptoms reported with any intensity were pain (48.9% and 31.0% of doses in the PHiD-CV and Control groups) and irritability (58.0% and 40.4% of doses in the PHiD-CV and Control groups). Within 31 days post-vaccination, the incidence of unsolicited symptoms was comparable in both groups (following 12.3% and 14.8% of doses in the PHiD-CV and Control groups, respectively). Throughout the study, 13 serious adverse events (SAEs) were reported in 9 infants in the PHiD-CV group and 11 SAEs in 6 infants in the Control group. None of them were fatal or
Zhou, Jian; Yang, Fan; Yang, Jinghui; Ma, Lei; Cun, Yina; Song, Shaohui; Liao, Guoyang
Vaccination is the practiced and accessible measure for preventing influenza infection. Because chicken embryos used for vaccine production have various insufficiencies, more efficient methods are needed. African green monkey kidney (Vero) cells are recommended by the World Health Organization (WHO) as a safe substitute for influenza vaccine production for humans. However, the influenza virus usually had low-yield in Vero cells, which limits the usage of Vero cellular vaccines. This study used 2 high-yield influenza viruses in Vero cells: A/Yunnan/1/2005Va (H3N2) and B/Yunnan/2/2005Va (B) as donor viruses. It used 3 wild strain viruses to reassort new adaptation viruses, including: A/Tianjin/15/2009(H1N1), A/Fujian/196/2009(H3N2), and B/Chongqing/1384/2010(B). These three new viruses could maintain the characteristic of high-yield in Vero cells. Furthermore, they could keep the immunogenic characteristics of the original wild influenza viruses. Importantly, these viruses were shown as safe in chicken embryo and guinea pigs assessment systems. These results provide an alternative method to produce influenza vaccine based on Vero cells.
Tsurudome, Yukari; Kimachi, Kazuhiko; Okada, Yusuke; Matsuura, Kenta; Ooyama, Yusuke; Ibaragi, Kayo; Kino, Yoichiro; Ueda, Kohji
Two antigenically distinct B strain lineages of influenza virus have co-circulated since the mid-1980s; however, inactivated trivalent influenza vaccines contain only one B lineage. The mismatch between the circulating and vaccine lineages has been a worldwide issue. In this study, an inactivated quadrivalent influenza vaccine (QIV) candidate containing two B lineages was manufactured and its immunogenicity and safety evaluated in an open-label, uncontrolled trial. In this phase II trial, 50 subjects aged 20-64 years received two doses of QIV s.c. 1 to 4 weeks apart. Sera were collected pre- and post-vaccination and safety assessed from the first vaccination to 21 ± 7 days after the second vaccination. After the first vaccination, hemagglutination inhibition titers against each strain increased markedly; the seroconversion rate, geometric mean titer ratio and seroprotection rate being 94.0%, 24.93, and 100.0%, respectively, for the A/H1N1pdm09 strain; 94.0%, 12.47, and 98.0%, respectively, for the A/H3N2 strain; 54.0%, 4.99, and 66.0%, respectively, for B/Yamagata strain, and 72.0%, 6.23 and 80.0%, respectively, for the B/Victoria strain, thus fulfilling the criteria of the European Medical Agency's Committee for Medicinal Products for Human Use. Also, the QIV induced sufficient single radial hemolysis and neutralizing antibodies against all four vaccine strains. No noteworthy adverse events were noted. The results of this trial demonstrate that QIV is well tolerated and immunogenic for each strain, suggesting that QIV potentially improves protection against influenza B by resolving the issue of B lineage mismatch.
A growing body of literature defends the efficacy of seasonal influenza vaccination for health care workers in reducing the mortality of hospitalized patients. I review the evidence concerning influenza vaccination, concluding that universal vaccination of health care workers against influenza should be considered standard patient care and that nonvaccination represents maleficent care. I further argue that the ethical responsibility to ensure universal vaccination of staff against seasonal influenza lies not only with individual health care providers but with each individual health care institution.
Mackenzie, Isla S; MacDonald, Thomas M; Shakir, Saad; Dryburgh, Moira; Mantay, Brian J; McDonnell, Patrick; Layton, Deborah
AIMS During the global H1N1 influenza A (swine flu) pandemic 2009–2010, swine flu vaccines were expeditiously licensed and a mass vaccination programme for high risk groups, including pregnant women, was introduced in the UK. This pilot active safety surveillance study was performed to establish the feasibility of rapidly monitoring the new swine flu vaccines in large patient numbers receiving or offered the vaccination under normal conditions of use within a short time frame. METHODS A cohort design with safety data capture through modern technologies was carried out in Scotland, UK during the winter swine flu vaccination programme 2009–2010 in individuals receiving or offered the swine flu vaccination. The main outcome measures were self-reported serious adverse events (SAEs) and pregnancy outcomes. RESULTS The cohort comprised 4066 people; 3754 vaccinated and 312 offered the vaccination but not vaccinated. There were 939 self-reported events (838 different events), 53 judged to fit SAE criteria by the investigators, with nine judged as possibly, probably or definitely vaccine related. None of the seven deaths (six in vaccinees) were judged as vaccine related. One hundred and twenty-eight women reported 130 pregnancies during the study with 117 pregnant at study start. There were reports of four miscarriages in three women and six possible congenital abnormalities in live births. CONCLUSIONS Overall, no significant safety issues were identified. The methodology and use of modern technologies to collect safety data from large numbers of patients was successful and could be used again in similar safety studies. PMID:22082196
Casajuana, Josep; Iglesias, Begoña; Fàbregas, Mireia; Fina, Francesc; Vallès, Joan-Antoni; Aragonès, Rosa; Benítez, Mència; Zabaleta, Edurne
Background Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Methods Design: Randomised, controlled, single blinded, multi-centre clinical trial. Setting: 4 primary care practices in Barcelona, Spain. Participants: 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 2003–2004 season. Interventions: intramuscular administration of influenza vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). Primary outcome: change in the circumference of the arm at the site of injection at 24 hours. Secondary outcomes: appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Results Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). Conclusion This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route. Registration number NCT00137579 at clinicaltrials.gov PMID:18507871
van den Berg, Thierry; Lambrecht, Bénédicte; Marché, Sylvie; Steensels, Mieke; Van Borm, Steven; Bublot, Michel
Although it is well accepted that the present Asian H5N1 panzootic is predominantly an animal health problem, the human health implications and the risk of human pandemic have highlighted the need for more information and collaboration in the field of veterinary and human health. H5 and H7 avian influenza (AI) viruses have the unique property of becoming highly pathogenic (HPAI) during circulation in poultry. Therefore, the final objective of poultry vaccination against AI must be eradication of the virus and the disease. Actually, important differences exist in the control of avian and human influenza viruses. Firstly, unlike human vaccines that must be adapted to the circulating strain to provide adequate protection, avian influenza vaccination provides broader protection against HPAI viruses. Secondly, although clinical protection is the primary goal of human vaccines, poultry vaccination must also stop transmission to achieve efficient control of the disease. This paper addresses these differences by reviewing the current and future influenza vaccines and vaccination strategies in birds.
Wong, Sook-San; Webby, Richard J
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.
Tsang, Peter; Gorse, Geoffrey J; Strout, Cynthia B; Sperling, Malcolm; Greenberg, David P; Ozol-Godfrey, Ayca; DiazGranados, Carlos; Landolfi, Victoria
We conducted a randomized, controlled, multicenter, phase II study to evaluate the immunogenicity and safety of an investigational intradermal (ID) trivalent influenza vaccine (TIV) and a high-dose (HD) intramuscular (IM) TIV in older adults (≥65 years of age). Older adult subjects were immunized with ID vaccine containing either 15μg hemagglutinin (HA)/strain (n=636) or 21μg HA/strain (n=634), with HD IM vaccine containing 60μg HA/strain (n=320), or with standard-dose (SD) IM vaccine (Fluzone(®); 15μg HA/strain; n=319). For comparison, younger adults (18-49 years of age) were immunized with SD IM vaccine. In older adults, post-vaccination geometric mean titers induced by the ID vaccines were superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains and non-inferior for the B strain. Seroconversion rates induced by the ID vaccines were superior to those induced by the SD IM vaccine in older adults for the A/H1N1 and B strains and non-inferior for the A/H3N2 strain. Results did not differ significantly for the two ID vaccine dosages. Post-vaccination geometric mean titers, seroconversion rates, and most seroprotection rates were significantly higher in HD vaccine recipients than in older adult recipients of the SD IM or ID vaccines and, for most measures, were comparable to those of younger adult SD IM vaccine recipients. Injection-site reactions, but not systemic reactions or unsolicited adverse events, were more common with the ID vaccines than with the IM vaccines. No treatment-related serious adverse events were reported. This study demonstrated that: (1) the ID and HD vaccines were well-tolerated and more immunogenic than the SD IM vaccine in older adults; (2) the HD vaccine was more immunogenic than the ID vaccines in older adults; and (3) the HD vaccine in older adults and the SD IM vaccine in younger adults elicited comparable antibody responses (ClinicalTrials.gov identifier no.: NCT00551031).
... Past Newsletters Selecting Viruses for the Seasonal Influenza Vaccine Language: English EspaÃ±ol Recommend on Facebook Tweet ... influence which viruses are selected for use in vaccine production? The influenza viruses in the seasonal flu ...
Soltani, Jafar; Jamil Amjadi, Mohamad
We studied the safety of a trivalent inactivated surface antigen (split virion, inactivated) influenza vaccine, Begrivac® (Novartis Company), widely used in health care workers in Kurdistan. A longitudinal follow-up study was performed in Sanandaj city, west of Iran, recruiting 936 people. A questionnaire was completed for each participant, and all symptoms or abnormal physical findings were recorded. In part 1 of the study, the post-vaccination complaints were headache (5.3%), fever (7.9%), weakness (9.6%), chills (10.1%), sweating (10.5%), arthralgia (20.2%), and malaise (21.5%). Swelling of the injection site was seen in 267 (30.3%) participants, and pruritus of the injection site was seen in 290 (32.9%) participants. Redness and induration were also reported in 42.5% of the participants. Local reactions were mainly mild and lasted for 1-2 days. No systemic reactions were reported in the second part of the study. None of the participants experienced any inconvenience. We concluded that local adverse reactions after the trivalent inactivated split influenza vaccine, Begrivac®, in health care workers were far more common than expected. Continuous surveillance is needed to assess the potential risks and benefits of newly produced influenza vaccines.
Beyer, W E P; Nauta, J J P; Palache, A M; Giezeman, K M; Osterhaus, A D M E
Several inactivated influenza vaccine formulations for systemic administration in man are currently available for annual (seasonal) immunization: split virus and subunit (either plain-aqueous, or virosomal, or adjuvanted by MF59). From a literature search covering the period 1978-2009, 33 articles could be identified, which described randomized clinical trials comparing at least two of the four vaccine formulations with respect to serum hemagglutination inhibition (HI) antibody response, local and systemic vaccine reactions and serious adverse events after vaccination, and employing seasonal vaccine components and doses. In total, 9121 vaccinees of all ages, either healthy or with underlying diseases, were involved. Most vaccinees were primed or had been vaccinated in previous years. For immunogenicity, homologous post-vaccination geometric mean HI titers (GMTs) were analyzed by a random effects model for continuous data. Unreported standard deviations (SD) were addressed by imputing assumed SD-values. Age and health state of the vaccinees appeared to have little influence on the outcome. The immunogenicity of split, aqueous and virosomal subunit formulations were similar, with geometric mean ratio values (GMR, quotient of paired GMT-values) varying around one (0.93-1.24). The MF59-adjuvanted subunit vaccine induced, on average, larger antibody titers than the non-adjuvanted vaccine formulations, but the absolute increase was small (GMR-values varying between 1.25 and 1.40). Vaccine reactions were analyzed using a random effects model for binary data. Local and systemic reactogenicity was similar among non-adjuvanted formulations. The adjuvanted subunit formulation was more frequently associated with local reactions than the non-adjuvanted formulations (rate ratio: 2.12, significant). Systemic reactions were similar among all vaccine formulations. The original articles emphasized the mild and transient character of the vaccine reactions and the absence of serious
Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della
Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–<3, 3–8, and 9–17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–<3 and 3–8 y cohorts. Among children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884
Pepin, Stephanie; Szymanski, Henryk; Rochín Kobashi, Ilya Angélica; Villagomez Martinez, Sandra; González Zamora, José Francisco; Brzostek, Jerzy; Huang, Li-Min; Chiu, Cheng-Hsun; Chen, Po-Yen; Ahonen, Anitta; Forstén, Aino; Seppä, Ilkka; Quiroz, René Farfán; Korhonen, Tiina; Rivas, Enrique; Monfredo, Celine; Hutagalung, Yanee; Menezes, Josemund; Vesikari, Timo
ABSTRACT A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3–8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3–8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain. PMID:27565435
Shope, Richard E.
Either living or heat-killed H. influenzae suis vaccines, given intramuscularly to swine, elicit an immune response capable of modifying the course of a later swine influenza infection. The protection afforded is only partial and is in no way comparable to the complete immunity afforded by swine influenza virus vaccines. PMID:19870654
Tripp, Ralph A.; Tompkins, S. Mark
Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278
Winokur, Patricia L; Patel, Shital M; Brady, Rebecca; Chen, Wilbur H; El-Kamary, Samer S; Edwards, Kathryn; Creech, C Buddy; Frey, Sharon; Keitel, Wendy A; Belshe, Robert; Walter, Emmanuel; Bellamy, Abbie; Hill, Heather
Influenza A(H5N1) vaccination strategies that improve the speed of the immunological response and cross-clade protection are desired. We compared the immunogenicity of a single 15-μg or 90-μg dose of A/H5N1/Indonesia/05/05 (clade 2) vaccine in adults who were previously primed with A/H5N1/Vietnam/1203/2004 (clade 1) vaccine. High-dose vaccine resulted in significantly higher titers to both clade 1 and 2 antigens. Clade 2 titers were unaffected by the previous dose of clade 1 vaccine. Low-dose priming with a mismatched pandemic influenza A(H5N1) vaccine would improve the rapidity, magnitude, and cross-reactivity of the immunological response following a single high-dose, unadjuvanted, pandemic vaccine.
Carmona Martinez, Alfonso; Salamanca de la Cueva, Ignacio; Boutet, Philippe; Vanden Abeele, Carline; Smolenov, Igor; Devaster, Jeanne-Marie
Background: There is a need for better vaccines and vaccine strategies to reduce the burden of influenza in very young children. Methods: This phase 1, open-label study assessed the reactogenicity, safety, and immunogenicity of an inactivated trivalent influenza vaccine (TIV) containing low doses of hemagglutinin antigen (7.5 µg each strain), adjuvanted with a tocopherol-based oil-in-water emulsion Adjuvant System (AS03). Influenza vaccine-naïve children aged 6–35 months were sequentially enrolled to receive TIV-AS03D (1.48 mg tocopherol) or TIV-AS03C (2.97 mg tocopherol), then a 6-month booster of conventional TIV. The primary endpoint was the incidence of fever (axillary temperature >38 °C) for 7 days post-vaccination. Immune responses were assessed by hemagglutination-inhibition (HI) assay. Results: Forty children were sequentially enrolled into the TIV-AS03D or the TIV-AS03C group. Fever >38.0 °C was reported in 5/20 (25.0%) and 7/20 (35.0%) children after the first and second doses of TIV-AS03D, respectively, and in 7/20 (35.0%) children after 1 dose of TIV-AS03C; the latter fulfilled the holding rule for safety, and the second dose of TIV-AS03C was cancelled. HI immune responses exceeded adult European licensure criteria for the immunogenicity, and all children had HI antibody titers ≥ 1:40 after 1 dose of TIV booster against booster strains. Conclusions: One dose of primary vaccine containing a low dose of antigen and AS03 may be a possible influenza vaccination strategy for young children. The relatively high frequency of fever warrants further investigation, although the generalizability of the findings are uncertain given that many of the children had antibody evidence suggesting recent infection with A(H1N1)pdm09. PMID:25424805
Hovden, Arnt-Ove; Cox, Rebecca Jane; Haaheim, Lars Reinhardt
Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record. Annual vaccination is therefore recommended for all individuals with serious medical conditions, like COPD, and protects the vaccinee against influenza illness and also against hospitalization and death. In COPD patients, influenza infection can lead to exacerbations resulting in reduced quality of life, hospitalization and death in the most severe cases. Although there is only limited literature on the use of influenza vaccination solely in COPD patients, there is clearly enough evidence to recommend annual vaccination in this group. This review will focus on influenza virus and prophylaxis with inactivated influenza vaccines in COPD patients and other "at risk" groups to reduce morbidity, save lives, and reduce health care costs.
submitting a licence application in Europe, a $US27.5 million payment for approval of a refrigerator-stable liquid formulation of FluMist and as much as $US50 million for licensing of FluMist internationally. In July 2003 MedImmune announced that it had received approximately $US28 million in milestone payments during Q2 of 2003 for the approval of FluMist. CSL Ltd of Australia will collaborate on the development, sale and distribution of MedImmune Vaccine's vaccine in Australia, New Zealand and certain countries in the South Pacific. MedImmune is to acquire vaccine research programmes in respiratory syncytial virus and cytomegalovirus from MedImmune Vaccines. The company's primary interest is in FluMist. In May 2002, MedImmune licensed exclusive rights to Crucell's proprietary human cell line PER.C6 for use in its influenza vaccine programmes. On 11 March 2002, American Home Products changed its name and the names of its subsidiaries Wyeth-Ayerst and Wyeth-Lederle to Wyeth. Wyeth's vaccines division is called Wyeth Vaccines. On 29 September 2000, Aviron announced that it had been awarded a $US2.7 million Challenge Grant from NIAID for development of vaccines against pandemic strains of influenza based on FluMist intranasal technology. The cold-adapted live influenza vaccine has been widely evaluated in the US and Japan since 1975 in clinical trials involving several thousand people. Aviron completed phase II clinical trials in adults in the US and phase III trials in US children aged 15-71 months. Additional phase III trials in adults and the elderly are ongoing. Aviron also commenced phase III trials to test the safety of its intranasal live vaccine in children with moderate to severe asthma. The vaccine is delivered using the AccuSpray nasal delivery system by Becton Dickinson, which will supply the system for FluMist through the 2001-2002 influenza season under an agreement with Aviron made in August 1998. On 7 March 2000, Aviron announced that Wyeth-Lederle Vaccines
Ahluwalia, Indu B; Singleton, James A; Jamieson, Denise J; Rasmussen, Sonja A; Harrison, Leslie
Since 2004, the American College of Obstetricians and Gynecologists (ACOG) and the Advisory Committee on Immunization Practices (ACIP) have recommended that pregnant women receive the seasonal influenza vaccine, regardless of pregnancy trimester, because of their increased risk for severe complications from influenza. However, the uptake of the influenza vaccine by pregnant women has been low. During the 2009-2010 influenza season, pregnant women were identified as a priority population to receive the influenza A (H1N1) 2009 (2009 H1N1) monovalent vaccine in addition to the seasonal influenza vaccine. In this issue, we highlight information from the 10 states that collected data using the survey administered by the Pregnancy Risk Assessment and Monitoring System (PRAMS) about seasonal vaccine coverage among women with recent live births and reasons for those who chose not to get vaccinated. The combined estimates from PRAMS of influenza vaccination coverage for the 2009-2010 season, which included data from October 2009 to March 2010, from 10 states were 50.7% for seasonal and 46.6% for 2009 H1N1 vaccine among women with recent live births. Among women who did not get vaccinated, reasons varied from worries about the safety of the vaccines for self and baby to not normally getting the vaccination. Further evaluation is needed on ways to increase influenza vaccination among pregnant women, effectively communicate the risk of influenza illness during pregnancy, and address women's concerns about influenza vaccination safety during pregnancy.
de Vries, R D; Altenburg, A F; Rimmelzwaan, G F
The extensive antigenic drift displayed by seasonal influenza viruses and the risk of pandemics caused by newly emerging antigenically distinct influenza A viruses of novel subtypes has raised considerable interest in the development of so-called universal influenza vaccines. We review options for the development of universal flu vaccines and discuss progress that has been made recently.
Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun
Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8(+) T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides 'self-adjuvanting' activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches.
Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun
Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8+ T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides ‘self-adjuvanting’ activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches. PMID:25876176
... is taken in its entirety from the CDC Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... flulive.html . CDC review information for Live, Intranasal Influenza VIS: Vaccine Information Statement Influenza Page last reviewed: ...
Mosterín Höpping, Ana; Fonville, Judith M; Russell, Colin A; James, Sarah; Smith, Derek J
Epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. The influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza A/H3N2, A/H1N1, and influenza B viruses. However, since the 1970s influenza B has split into two antigenically distinct lineages, only one of which is represented in the annual trivalent vaccine at any time. We describe a lineage selection strategy that optimizes protection against influenza B using the standard trivalent vaccine as a potentially cost effective alternative to quadrivalent vaccines.
McEvoy, Suzanne P
In Australia, annual vaccination with trivalent influenza vaccine (TIV) is recommended for healthcare providers. Each year, an influenza vaccination program is run in south metropolitan area hospitals in Perth, Western Australia. In 2010, a survey to examine side effects following vaccination and subsequent significant respiratory illnesses during the influenza season was undertaken. A total of 2245 individuals vaccinated in the area-wide hospital vaccination program responded, representing 50% of consenting recipients. Data linkage was performed to ascertain additional information such as brand details. Side effects within 48 h of receipt of the influenza vaccine were reported by 387 (17.2%). Only 30 respondents (1.3%) had to seek health advice following a side effect temporally related to influenza vaccination and 10 (0.4%) required treatment. Recipients who received Fluvax®(364, 18.0%; CSL Biotherapies) were more likely to report side effects than those who received another brand (23, 10.2%; OR 1.94, 95% CI 1.24-3.03, P=0.004). The difference in the side effect profiles was largely confined to systemic effects. Most respondents (1621, 72.2%) did not require time off work for a respiratory illness during the subsequent influenza season. Overall, the influenza vaccine was demonstrated to be safe among this large sample of predominantly healthcare workers. A higher rate of adverse events, albeit primarily mild, was reported among recipients of Fluvax® in 2010.
Limited production capacity and delays in vaccine development are major obstacles to vaccination programs that are designed to mitigate a pandemic influenza. In order to evaluate and compare the impact of various vaccination strategies during a pandemic influenza, we developed an age/risk-structured model of influenza transmission, and parameterized it with epidemiological data from the 2009 H1N1 influenza A pandemic. Our model predicts that the impact of vaccination would be considerably diminished by delays in vaccination and staggered vaccine supply. Nonetheless, prioritizing limited H1N1 vaccine to individuals with a high risk of complications, followed by school-age children, and then preschool-age children, would minimize an over-all attack rate as well as hospitalizations and deaths. This vaccination scheme would maximize the benefits of vaccination by protecting the high-risk people directly, and generating indirect protection by vaccinating children who are most likely to transmit the disease. PMID:21361402
Influenza is associated with substantial morbidity and mortality each year in the United States. From 1976 to 2007, annual deaths from influenza ranged from approximately 3,300 to 49,000. Vaccination against influenza has been recommended to prevent illness and related complications, and since 2010, the Advisory Committee on Immunization Practices has recommended that all persons aged ≥6 months be vaccinated against influenza each year. In 2013, CDC published a model to quantify the annual number of influenza-associated illnesses and hospitalizations averted by influenza vaccination during the 2006-11 influenza seasons. Using that model with 2012-13 influenza season vaccination coverage rates, influenza vaccine effectiveness, and influenza hospitalization rates, CDC estimated that vaccination resulted in 79,000 (17%) fewer hospitalizations during the 2012-13 influenza season than otherwise might have occurred. Based on estimates of the percentage of influenza illnesses that involve hospitalization or medical attention, vaccination also prevented approximately 6.6 million influenza illnesses and 3.2 million medically attended illnesses. Influenza vaccination during the 2012-13 season produced a substantial reduction in influenza-associated illness. However, fewer than half of persons aged ≥6 months were vaccinated. Higher vaccination rates would have resulted in prevention of a substantial number of additional cases and hospitalizations.
Altay, Fatma Aybala; Güz, Galip; Altay, Mustafa
abstract A peritoneal dialysis patient who experienced a repeating attack after a vaccination for influenza while she was being followed and treated succesfully for subacute thyroiditis (SAT) is presented. This case shows SAT as a rare condition following vaccination.. Thus, SAT should be considered as a possible outcome following influenza vaccination and flu-like syndrome. PMID:26809709
Mulligan, Mark J.; Bernstein, David I.; Frey, Sharon; Winokur, Patricia; Rouphael, Nadine; Dickey, Michelle; Edupuganti, Srilatha; Spearman, Paul; Anderson, Edwin; Graham, Irene; Noah, Diana L.; Mangal, Brian; Kim, Sonnie; Hill, Heather; Whitaker, Jenifer; Emery, William; Beck, Allison; Stephens, Kathy; Hartwell, Brooke; Ogilvie, Melinda; Rimann, Nayoka; Osinski, Eileen; Destefano, Ellen; Gajadhar, Theda; Strudwick, Amanda; Pierce, Karen; Lai, Lilin; Yue, Ling; Wang, Dongli; Ying, Carl; Cline, Amy; Foltz, Tara; Wagner, Nancy; Dull, Geraldine; Pacatte, Thomas; Taggart, Barbara; Johnson, Valerie; Haller, Logan; Looney, Candi; Li, Shixiong; May, Megan; Myers, Bridgette; May, Rachel; Parker, Lawanda; Cochran, Nertaissa; Bowen, Donna; Bell, Michelle; Scoggins, Jeffery; Burns, Angela; Stablein, Claire; Wolff, Mark; Jolles, Bernadette; Leung, Brenda; Lambert, Linda; Shorer, Shy; Buchanan, Wendy; Murray, Suzanne; Chang, Soju; Gorman, Richard
Background Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs. Methods A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant. Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18–49 years. Results Two hundred and seventy subjects were enrolled. After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001). Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher. Vaccine + MF59 produced cross-reactive antibody responses against 4 heterologous H5N1 viruses. Excellent safety and tolerability were demonstrated. Conclusions Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe. The feasibility of the point-of-use mixing should be studied further. PMID:25734170
The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.
The influenza pandemic of 2009 demonstrated the inability of the established global capacity for egg-based vaccine production technology to provide sufficient vaccine for the population in a timely fashion. Several alternative technologies for developing influenza vaccines have been proposed, among which non-replicating virus-like particles (VLPs) represent an attractive option because of their safety and immunogenic characteristics. VLP vaccines against pandemic influenza have been developed in tobacco plant cells and in Sf9 insect cells infected with baculovirus that expresses protein genes from pandemic influenza strains. These technologies allow rapid and large-scale production of vaccines (3-12 weeks). The 2009 influenza outbreak provided an opportunity for clinical testing of a pandemic influenza VLP vaccine in the midst of the outbreak at its epicenter in Mexico. An influenza A(H1N1)2009 VLP pandemic vaccine (produced in insect cells) was tested in a phase II clinical trial involving 4,563 healthy adults. Results showed that the vaccine is safe and immunogenic despite high preexisting anti-A(H1N1)2009 antibody titers present in the population. The safety and immunogenicity profile presented by this pandemic VLP vaccine during the outbreak in Mexico suggests that VLP technology is a suitable alternative to current influenza vaccine technologies for producing pandemic and seasonal vaccines.
Painter, Julia E.; Sales, Jessica M.; Pazol, Karen; Wingood, Gina M.; Windle, Michael; Orenstein, Walter A.; DiClemente, Ralph J.
Background: School-based vaccination programs may provide an effective strategy to immunize adolescents against influenza. This study examined whether adolescent attitudes toward influenza vaccination mediated the relationship between receipt of a school-based influenza vaccination intervention and vaccine uptake. Methods: Participants were…
Goodman, Kenneth; Mossad, Sherif B.; Taksler, Glen B.; Emery, Jonathan; Schramm, Sarah; Rothberg, Michael B.
Objective Despite influenza vaccination being an integral part of prenatal care, vaccination rates remain low. We evaluated the impact of pre-visit video education on patients' vaccination health beliefs and vaccination rate. Study design From November 2013-January 2014, unvaccinated patients seen for routine prenatal care were randomized to pre-visit vaccination video education or control. Pre and post video health beliefs were assessed on a 5-point scale and unvaccinated participants were subsequently interviewed by phone. Results In 105 randomized participants, intervention positively influenced health beliefs as demonstrated by differences in mean pre- vs. post scores for intervention vs. control: vaccination may harm mother (difference =-0.05, p=0.009) and baby (difference=-0.44, p=0.015), and vaccination can protect mother (difference=0.49, p=0.003) and baby (difference=0.59, p=0.001). Vaccination rates were 28% intervention and 25% control (p=0.70). Provider recommendation was associated with vaccination (47% if recommended vs.12% if not, p<.001). Phone interviews revealed susceptibility to influenza and vaccine safety as primary reasons for remaining unvaccinated Conclusions Video education positively influenced vaccination health beliefs without impacting vaccination rates. Physician's recommendation was strongly associated with participant's decision to become and may be most effective when emphasizing influenza vaccination's protective impact on the newborn. PMID:26775454
Shi, Nianmin; Luo, Feng-Ji; Li, Li; Zheng, Dongyi; Zhang, Zheng; Wang, Zhao-Yun; Yang, Liqing; Liu, Zhaoqiu; Ai, Xing; Bai, Yunhua; Lu, Qiang
To compare the safety and immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccine administered via the vastus lateralis and deltoid muscles, 320 healthy Chinese infants <12 mo of age were enrolled in a randomized, controlled, blinded study and divided into 2 age groups: 2–5 mo and 6–12 mo. Each age group was then randomized (1:1) to either the vastus lateralis (experimental) group who received Hib vaccination into this muscle 2 or 3 times at monthly intervals, or the deltoid (control) group who received Hib vaccination into this muscle either 3 times (2–5 mo group) or twice (6–12 mo group) at monthly intervals. Local and systemic adverse reactions after each vaccine dose were recorded, and Hib-PRP antibody concentrations were determined by ELISA at 28 d after completion of the immunization schedule. There were no significant differences in the proportions of subjects with post-immunization Hib-PRP antibody concentrations ≥1.0 μg/mL or ≥0.15 μg/mL with the two injection sites for either age group, or in the post-immunization Hib-PRP antibody concentrations achieved (P > 0.05). In addition, there were no significant differences in the rates of local and systemic reactions after the first and second vaccinations between the 2 injection sites for either age group (P > 0.05), but the rate of systemic reactions in the 2–5 mo group after the third vaccination via the vastus lateralis muscle was significantly lower than after deltoid vaccination (0% vs 8.57%; P < 0.05). Thus, administration via the vastus lateralis muscle is worth considering for Hib vaccination. PMID:23842003
Pregliasco, F.; Sodano, L.; Mensi, C.; Selvaggi, M. T.; Adamo, B.; D'Argenio, P.; Giussani, F.; Simonetti, A.; Carosella, M. R.; Simeone, R.; Dentizi, C.; Montanaro, C.; Ponzio, G.
This article surveys the attitudes and perceptions of a random sample of the elderly population in three regions of Italy on the use and efficacy of influenza vaccine. The data were collected by direct interviews using a standard questionnaire. The results show that vaccination coverage against influenza is inadequate (26-48.6%). The major reasons for nonvaccination were lack of faith in the vaccine and disbelief that influenza is a dangerous illness. These data emphasize the need for a systematic education programme targeted at the elderly and the provision of influenza vaccination, with the increased cooperation of general practitioners. PMID:10083710
de Vries, Rory D; Altenburg, Arwen F; Rimmelzwaan, Guus F
Currently used influenza vaccines are only effective when the vaccine strains match the epidemic strains antigenically. To this end, seasonal influenza vaccines must be updated almost annually. Furthermore, seasonal influenza vaccines fail to afford protection against antigenically distinct pandemic influenza viruses. Because of an ever-present threat of the next influenza pandemic and the continuous emergence of drift variants of seasonal influenza A viruses, there is a need for an universal influenza vaccine that induces protective immunity against all influenza A viruses. Here, we summarize some of the efforts that are ongoing to develop universal influenza vaccines.
Alvarez, I; Corral, J; Arranz, A; Foruria, A; Landa, V; Lejarza, J R; Marijuán, L; Martínez, J M
The present study investigated the level of immunity of the population against three strains of the influenza virus (A Chile/1/83 -A Philippines/2/82 and B URSS/100/83) before and three months after vaccination, and the immune response to whole virus vaccine as compared with fragmented virus vaccine. A high percentage of the population had titers greater than or equal to 1/10 before vaccination for the Chile (54%) and Philippines (65.7%) strains, while titers against the URSS strain were lower (25.4%). There was a definitive increase in antibody titer in the vaccinated population, although it was lower than expected. The overall response to both vaccines, with protecting titers greater than or equal to 1/40 after vaccination was 65.2% for the Chile strain, 74.6% for the Philippines strain, and 15% for the URSS strain. No differences in the overall immune response were found between the groups vaccinated with whole and fragmented virus.
Frenck, Robert W; Belshe, Robert; Brady, Rebecca C; Winokur, Patricia L; Campbell, James D; Treanor, John; Hay, Christine M; Dekker, Cornelia L; Walter, Emmanuel B; Cate, Thomas R; Edwards, Kathryn M; Hill, Heather; Wolff, Mark; Leduc, Tom; Tornieporth, Nadia
The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed. Previously healthy subjects 18-64 years of age were randomly assigned to one of four TIV vaccine groups: standard 15 μg HA/strain TIV IM, either 9 μg or 6 μg HA/strain of TIV ID given using a new microinjection system (BD Soluvia™ Microinjection System), or 3 μg HA/strain of TIV ID given by Mantoux technique. All vaccines contained A/New Caledonia (H1N1), A/Wyoming (H3N2) and B/Jiangsu strains of influenza. Sera were obtained 21 days after vaccination and hemagglutination inhibition (HAI) assays were performed and geometric mean titers (GMT) were compared among the groups. Participants were queried immediately following vaccination regarding injection pain and quality of the experience. Local and systemic reactions were collected for 7 days following vaccination and compared. Ten study sites enrolled 1592 subjects stratified by age; 18-49 years [N=814] and 50-64 years [N=778]. Among all subjects, for each of the three vaccine strains, the GMTs at 21 days post-vaccination for both the 9 μg and the 6 μg doses of each strain given ID were non inferior to GMTs generated after standard 15 μg doses/strain IM. However, for the 3 μg ID dose, only the A/Wyoming antigen produced a GMT that was non-inferior to the standard IM dose. Additionally, in the subgroup of subjects 50-64 years of age, the 6μg dose given ID induced GMTs that were inferior to the standard IM TIV for the A/H1N1 and B strains. No ID dose produced a GMT superior to that seen after standard
Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele
Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011–2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P < 0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011–2012 season (P < 0.001). “To avoid spreading influenza among patients” was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future. PMID:24603089
Frey, Sharon E.; Bernstein, David I.; Gerber, Michael A.; Keyserling, Harry L.; Munoz, Flor M.; Winokur, Patricia L.; Turley, Christine B.; Rupp, Richard E.; Hill, Heather; Wolff, Mark; Noah, Diana L.; Ross, Allison C.; Cress, Gretchen; Belshe, Robert B.
Background. Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children. Methods. Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. Results. All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine. Conclusions. Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age. Clinical Trials Registration. NCT00943202. PMID:22802432
Luo, Feng-Ji; Yang, Li-Qing; Ai, Xing; Bai, Yun-Hua; Wu, Jiang; Li, Shu-Ming; Zhang, Zheng; Lu, Min; Li, Li; Wang, Zhao-Yun; Shi, Nian-Min
The 2009 influenza A(H1N1) pandemic strain was for the first time included in the 2010-2011 seasonal trivalent influenza vaccine (TIV). We conducted a double-blind, randomized trial in Chinese population to assess the immunogenicity and safety of the 2010-2011 TIV manufactured by GlaxoSmithKline and compared it with the counterpart vaccines manufactured by Sanofi Pasteur and Sinovac Biotech. Healthy toddlers (6-36 mo), children (6-12 y) and older adults (≥60 y) with 300 participants in each age group were enrolled to randomly receive two doses (toddlers, 28 d apart) or one dose (children and older adults). The immunogenicity was assessed by hemagglutination-inhibition (HI) assay. The solicited injection-site and systemic adverse events (AEs) were collected within 7 d after vaccination. All the three TIVs were well-tolerated with 15.1% of participants reporting AEs, most of which were mild. No serious AEs and unusual AEs were reported. Fever and pain were the most common systemic and injection-site AEs, respectively. The three TIVs showed good immunogenicity. The seroprotection rates against both H1N1 and H3N2 strains were more than 87% in toddlers after two doses and more than 95% in children and more than 86% in older adults after one dose. The seroprotection rates against B strain were 68-71% in toddlers after two doses, 70-74% in children and 69-72% in older adults after one dose. In conclusion, the three 2010-2011 TIVs had good immunogenicity and safety in Chinese toddlers, children and older adults and were generally comparable in immunogenicity and reactogenicity.
Tomar, Jasmine; Born, Philip A; Frijlink, Henderik W; Hinrichs, Wouter L J
Cold-chain requirements, limited stockpiling potential and the lack of potent immune responses are major challenges of parenterally formulated influenza vaccines. Decreased cold chain dependence and stockpiling can be achieved if vaccines are formulated in a dry state using suitable excipients and drying technologies. Furthermore, having the vaccine in a dry state enables the development of non-parenteral patient friendly dosage forms: microneedles for transdermal administration, tablets for oral administration, and powders for epidermal, nasal or pulmonary administration. Moreover, these administration routes have the potential to elicit an improved immune response. This review highlights the rationale for the development of dried influenza vaccines, as well as processes used for the drying and stabilization of influenza vaccines; it also compares the immunogenicity of dried influenza vaccines administered via non-invasive routes with that of parenterally administered influenza vaccines. Finally, it discusses unmet needs, challenges and future developments in the field of dried influenza vaccines.
Zverev, V V; Katlinskiĭ, A V; Kostinov, M P; Zhirova, S N; Erofeeva, M K; Stukova, M A; Korovkin, S A; Mel'nikov, S Ia; Semchenko, A V; Mironov, A N
Scientic-production association "Microgen" has finished 1st phase of clinical trials of candidate vaccines against avian influenza in order to assess their reactogenicity, safety, and immunogenicity. Two vaccines constructed from NIBRG-14 vaccine strain [A/Vietnam/1 194/2004 (H5N1)], obtained from World Health Organization, were studied: "OrniFlu" (inactivated subunit influenza vaccine adsorbed on aluminium hydroxide) and inactivated polymer-subunit influenza vaccine with polyoxydonium (IPSIV). Clinical trial of the vaccines with different quantity of antigen (15, 30, and 45 mcg of H5N1 virus hemagglutinin) was carried out in Influenza Research Institute (St. Petersburg) and in Mechnikov Research Institute of Vaccines and Sera (Moscow). Analysis of results allowed to conclude that both vaccines were safe, well tolerated and characterized by low reactogenicity. Two-doses vaccination schedule was needed to meet required seroconversion and seroprotection rates (> or =1:40 in > or =70% of vaccinated volunteers). "Orni-Flu" vaccine containing 15 mcg of hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) in one dose as well as IPSIV containing 45 mcg of hemagglutinin and 0.75 mg of polyoxydonium in one dose were most immunogenic after 2 doses - seroprotection rates in microneutralization assay were 72.2% and 77.0% respectively. Marked influence of aluminium hydroxide content on immunogenicity of the "OrniFlu" vaccine was confirmed in the study. Optimal quantity of adjuvant was 0.5 mg per dose. According to basic concept of vaccine development, preference is given to vaccine that under minimal quantity of antigen induces sufficient specific immune response and is safe in volunteers. "OrniFlu" vaccine containing 15 mcg of H5N1 virus hemagglutinin and optimal quantity of aluminium hydroxide (0.5 mg) corresponded to these requirements that allowed researchers to recommend it for clinical trials of 2nd phase.
Mossad, Sherif B
Faced with a shortage of the inactivated intramuscular influenza vaccine this year, the Centers for Disease Control and Prevention (CDC) has revised its guidelines for immunization and use of antiviral agents. The most rational solution at this time is to direct the supply of scarce vaccine to patients at highest risk of influenza-related complications.
Hirota, Yoshio; Kaji, Masaro
In 1976, influenza mass vaccination among schoolchildren was started under the Preventive Vaccination Law, which was intended to control epidemics in the community. However, in the late 1980s, questions about this policy and vaccine efficacy arose, and a campaign against vaccination began. In 1994, influenza was excluded from the target diseases list in the Preventive Vaccination Law, without considering the immunization policy with respect to the common indications in high-risk groups. In 2001, the Law was again amended, specifying target groups, such as the elderly aged 65 or over, for influenza vaccination. In the 2005--2006 season, vaccine coverage among the elderly reached 52%. This shows that the need for vaccination has gradually become understood. However, the anti-vaccination campaign, which claims that the influenza vaccine has no efficacy, is still active. Vaccine efficacy studies that were not properly conducted are also being reported. In 2002, the Ministry of Health, Labor, and Welfare organized a research group on vaccine efficacy consisting of epidemiologists. The present symposium, as part of the 9th Annual Meeting of the Japanese Society for Vaccinology in 2005, was planned to further introduce epidemiological concepts useful in studying influenza vaccine efficacy.
... HUMAN SERVICES Office of the Secretary Pandemic Influenza Vaccines--Amendment ACTION: Notice of... influenza vaccines, which has been amended a number of times. The original pandemic influenza vaccine... (2010). The major actions taken by this pandemic influenza vaccine declaration are the following:...
Shen, Yonggang; Hu, Yuansheng; Meng, Fanya; Du, Wenjun; Li, Wei; Song, Yufei; Ji, Xiaoci; Huo, Liqun; Fu, Zhenping; Yin, Weidong
ABSTRACT Anflu® is a seasonal trivalent inactivated split-virion influenza vaccine manufactured by Sinovac Biotech Co., Ltd. The objectives of this study were to evaluate the safety of Anflu® (2013–14 formulation: H1N1, H3N2 and BYAM) in infants and adults and its immunogenicity and cross-reactivity against mismatched influenza B lineage and avian influenza A(H7N9) viruses (hereafter BVIC and H7N9, respectively) in adults. In this phase IV open label trial, infants 6–35 months old (n=61) each received two injections with 28 days apart; adults 18–60 yrs old (n=60) and elderly >60 yrs old (n=61) each received one injection. Information of adverse events was collected through safety observation and follow-up visits. Pre- and post-immune blood samples (day 0 and 21) were collected from subjects ≥18 yrs old to detect hemagglutination inhibition antibody titers and calculate seroprotection rates (SPRs) and seroconversion rates (SCRs). The overall adverse reaction incidence was 1.6% (3/182), and no serious adverse event was reported during the study period. For subjects ≥18 yrs old, the SCRs, SPRs, and the geometric mean titers (GMTs) met the European criteria for all three strains. In addition, the point estimations of SCR, SPR and GMT for BVIC also met the European criteria. Six subjects were seroconverted against H7N9; however the serological results did not meet the European criteria. In conclusion, the results showed a satisfactory safety and immunogenicity profile of Anflu® and cross-reactivity against BVIC, but did not demonstrate cross-reactivity against H7N9 (Clinicaltrials.gov ID: NCT02269852). PMID:26934750
Jackson, Lisa A.; Chen, Wilbur H.; Stapleton, Jack T.; Dekker, Cornelia L.; Wald, Anna; Brady, Rebecca C.; Edupuganti, Srilatha; Winokur, Patricia; Mulligan, Mark J.; Keyserling, Harry L.; Kotloff, Karen L.; Rouphael, Nadine; Noah, Diana L.; Hill, Heather; Wolff, Mark C.
Background. Adjuvanted vaccines have the potential to improve influenza pandemic response. AS03 adjuvant has been shown to enhance the immune response to inactivated influenza vaccines. Methods. This trial was designed to evaluate the immunogenicity and safety of an inactivated 2009 H1N1 influenza vaccine at varying dosages of hemagglutinin with and without extemporaneously mixed AS03 adjuvant system in adults ≥18 years of age. Adults were randomized to receive 2 doses of 1 of 5 vaccine formulations (3.75 µg, 7.5 µg, or 15 µg with AS03 or 7.5 µg or 15 µg without adjuvant). Results. The study population included 544 persons <65 years of age and 245 persons ≥65 years of age. Local adverse events tended to be more frequent in the adjuvanted vaccine groups, but severe reactions were uncommon. In both age groups, hemagglutination inhibition antibody geometric mean titers after dose one were higher in the adjuvanted groups, compared with the 15 µg unadjuvanted group, and this difference was statistically significant for the comparison of the 15 µg adjuvanted group with the 15 µg unadjuvanted group. Conclusions. AS03 adjuvant system improves the immune response to inactivated 2009 H1N1 influenza vaccine in both younger and older adults and is generally well tolerated. ClinicalTrials.gov NCT00963157 PMID:22782949
Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study
Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay
abstract The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children <2 years of age (mean age: 15.8 months). During the 4-day follow-up period, pain (31.7%) and redness (27.3%) were the most frequent solicited local symptoms. Pain (2%) was also the most frequent grade 3 local symptom. One subject reported 2 serious adverse events that were not causally related to the study vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years. PMID:26337197
Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.
Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay
The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children <2 years of age (mean age: 15.8 months). During the 4-day follow-up period, pain (31.7%) and redness (27.3%) were the most frequent solicited local symptoms. Pain (2%) was also the most frequent grade 3 local symptom. One subject reported 2 serious adverse events that were not causally related to the study vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years.
The influenza pandemic of 2009 demonstrated the inability of the established global capacity for egg-based vaccine production technology to provide sufficient vaccine for the population in a timely fashion. Several alternative technologies for developing influenza vaccines have been proposed, among which non-replicating virus-like particles (VLPs) represent an attractive option because of their safety and immunogenic characteristics. VLP vaccines against pandemic influenza have been developed in tobacco plant cells and in Sf9 insect cells infected with baculovirus that expresses protein genes from pandemic influenza strains. These technologies allow rapid and large-scale production of vaccines (3–12 weeks). The 2009 influenza outbreak provided an opportunity for clinical testing of a pandemic influenza VLP vaccine in the midst of the outbreak at its epicenter in Mexico. An influenza A(H1N1)2009 VLP pandemic vaccine (produced in insect cells) was tested in a phase II clinical trial involving 4,563 healthy adults. Results showed that the vaccine is safe and immunogenic despite high preexisting anti-A(H1N1)2009 antibody titers present in the population. The safety and immunogenicity profile presented by this pandemic VLP vaccine during the outbreak in Mexico suggests that VLP technology is a suitable alternative to current influenza vaccine technologies for producing pandemic and seasonal vaccines. PMID:22330956
Bayas Rodríguez, José M; García-Basteiro, Alberto L; Mena Pinilla, Guillermo
Given the threat of an avian influenza A (H5N1) pandemic, vaccines that could be used in a new influenza pandemic began to be developed in 2004. The possible pandemic scenarios included highly serious situations with high incidence and mortality. Due to the need for the greatest possible number of vaccines to be available in a short period of time, studies with "model" vaccines were started, which allowed the immunogenicity and safety of the vaccines to be determined before identifying which virus would cause the pandemic. The use of adjuvants also formed part of these strategies. Subsequently, studies with the pandemic A (H1N1) strain were performed and additional studies continue to be performed. The vaccination strategies adopted have not been aimed at containing the infection but rather at ameliorating its effects. The choice of candidate groups for vaccination was not made hastily but after evaluating a large body of information on the epidemiology of the disease and the characteristics of the available vaccines. The population to be vaccinated is basically the same as that recommended to undergo seasonal influenza vaccination. In the ethical context of primum non nocere special emphasis has been placed on the vaccination of health personnel. All the available information supports the safety of the adjuvants and preservatives used in some of the authorized vaccines, as stated by the World Health Organization and many other prestigious organizations. So far 65 million doses have been administered throughout the world and the various adverse events detected by surveillance systems have been similar to those observed with other influenza vaccines and those that could be expected among millions of persons. Lessons must be drawn from the course of the present pandemic and the strategies used to deal with this situation as there will be other pandemics.
Montana, Marc; Verhaeghe, Pierre; Ducros, Caroline; Terme, Thierry; Vanelle, Patrice; Rathelot, Pascal
Few studies show the reluctance of the people to get vaccinated against A (H1N1) influenza for fear of side effects of squalene (MF59, AS03, AF03) and thimerosal. The aim of this paper is to assess the safety in using these adjuvants and preservative reviewing data of clinical trials relative to which formulation includes these compounds. In the current state of knowledge, these vaccines have proved to be effective even though they more frequently give local adverse events than non-adjuvanted influenza vaccines. Systemic side effects are generally not serious. In the studies, adjuvanted vaccines do not increase neither the risk of Guillain Barre syndrome nor auto-immune diseases. There is no convincing evidence that exposure to thimerosal in vaccines had any deletorious effect on physiological outcome.
García-Basteiro, Alberto L; Alvarez-Pasquín, María-José; Mena, Guillermo; Llupià, Anna; Aldea, Marta; Sequera, Victor-Guillermo; Sanz, Sergi; Tuells, Jose; Navarro-Alonso, José-Antonio; de Arísteguí, Javier; Bayas, José-María
Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required.
Sullivan, Seth J; Jacobson, Robert; Poland, Gregory A
On 23 December 2009, the US FDA approved Fluzone® High Dose, a high-dose formulation of the trivalent inactivated influenza vaccine, for prevention of influenza in people 65 years of age and older. As it was approved via an accelerated process designed to allow expeditious availability of safe and effective products with promise to treat or prevent serious or life-threatening diseases, the manufacturer is required to conduct further studies to demonstrate effectiveness. Although these studies are underway, a recently completed randomized, controlled trial demonstrated that this vaccine, containing four-times more hemagglutinin than standard-dose inactivated influenza vaccines, can produce an enhanced immunologic response in subjects of 65 years of age and older, while maintaining a favorable safety profile. This article introduces the vaccine, presents currently available safety and immunogenicity data, discusses current recommendations for use, and proposes what we can expect in the coming years.
Soleimani, Sina; Shahsavandi, Shahla; Maddadgar, Omid
Immunization with DNA vaccines as a novel alternative to conventional vaccination strategy requires adjuvant for improving vaccine efficacy. The conserved immunogenic HA2 subunit, which harbors neutralizing epitopes is a promising vaccine candidate against influenza viruses. In this study, for the first time we explore the idea of using host interferon inducible Mx protein to increase the immunogenicity of HA2 H9N2 influenza DNA vaccine. The potency and safety of the Mx adjuvanted-HA2 vaccine was evaluated in BALB/c mice by different prime-boost strategies. To assess the effect of the vaccination on the virus clearance rate, mice were challenged with homologous influenza virus. Administration of the adjuvanted vaccine and boosting with the same regimen could effectively enhance both humoral and cellular immune responses in treated mice. These data demonstrated that Mx as host defense peptide can be potentiated for improving influenza vaccine efficacy.
Lagos, Rosanna E; Muñoz, Alma E; Levine, Myron M; Lepetic, Alejandro; François, Nancy; Yarzabal, Juan Pablo; Schuerman, Lode
The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™) were assessed in 240 healthy Chilean children randomized to receive 3 doses of PHiD-CV (PHiD-CV group) or hepatitis A vaccine (HAV control group) at 2-4-6 months of age. All were offered 1 HAV dose at 12 months (outside study). The PHiD-CV group received a second HAV dose at 18-21 months and PHiD-CV booster at 20-23 months. The HAV control group received 2 PHiD-CV catch-up doses at 18-21 and 20-23 months. Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured. Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary, booster and catch-up doses was in line with previous PHiD-CV studies, although generally higher than with HAV. For each vaccine serotype, the percentage of subjects with antibody concentrations ≥0.2 µg/ml (GSK's 22F-inhibition ELISA) was at least 93.2% following 3 PHiD-CV primary doses and at least 97.4% post-booster; percentages with OPA titers ≥8 were at least 91.7% post-booster. After 2-dose catch-up, at least 94.3% of children had antibody concentrations ≥0.2 µg/ml against each serotype except 6B (84.3%); at least 95.2% had OPA titers ≥8 except against serotypes 1, 5 and 6B. In conclusion, the safety profiles of 2 PHiD-CV vaccination schedules (3-dose primary plus booster and 2-dose catch-up) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein D.
Lin, Chyongchiou J; Nowalk, Mary Patricia; Toback, Seth L; Rousculp, Matthew D; Raymund, Mahlon; Ambrose, Christopher S; Zimmerman, Richard K
This randomized cluster trial was designed to improve workplace influenza vaccination rates using enhanced advertising, choice of vaccine type (intranasal or injectable) and an incentive. Workers aged 18-49 years were surveyed immediately following vaccination to determine factors associated with vaccination behavior and choice. The questionnaire assessed attitudes, beliefs and social support for influenza vaccine, demographics, and historical, current, and intentional vaccination behavior. Of the 2389 vaccinees, 83.3% received injectable vaccine and 16.7% received intranasal vaccine. Factors associated with previous influenza vaccination were older age, female sex, higher education and greater support for injectable vaccine (all P<.02). Current influenza vaccination with intranasal vaccine vs. injectable vaccine was associated with higher education, the study interventions, greater support for the intranasal vaccine and nasal sprays, less support of injectable vaccine, more negative attitudes about influenza vaccine, and a greater likelihood of reporting that the individual would not have been vaccinated had only injectable vaccine been offered (all P<.01). Intentional vaccine choice was most highly associated with previous vaccination behavior (P<.001). A key to long term improvements in workplace vaccination is to encourage first time influenza vaccination through interventions that include incentives, publicity and vaccine choice.
Choi, Hyo-Jick; Yoo, Dae-Goon; Bondy, Brian J.; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo; Prausnitz, Mark R.
A microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to intramuscular injection. Previous studies of microneedles have demonstrated effective vaccination using freshly prepared microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the microneedle coating matrix damages influenza vaccine coated onto microneedles. In vitro showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated microneedles. PMID:22361098
Shahrabani, Shosh; Benzion, Uri
This study examines the impact of past experience with influenza and the influenza vaccine on four categories of the Health Belief Model: beliefs about susceptibility to contracting influenza, severity of illness, perceived benefits of the vaccine in preventing influenza, and perceived barriers to getting vaccinated. The study population comprised…
Ortiz de Lejarazu, Raúl; Tamames, Sonia
Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics.
Huang, Yafang; Wang, Huili; Wan, Ling; Lu, Xiaoqin; Tam, Wilson W S
There are conflicts on whether influenza vaccinated systemic lupus erythematosus (SLE) patients are associated with a decreased immunogenicity and safety, compared with healthy controls. We conducted meta-analyses to compare SLE patients with healthy controls for flu-vaccine immunogenicity, as well as for adverse events.PubMed, MEDLINE, and Cochrane Library were searched by October 15, 2015. Studies were included when they met the inclusion criteria. Two reviewers independently extracted data on study characteristics, methodological quality, and outcomes. The primary outcome was seroprotection (SP) rate after immunization.A total of 15 studies were included. There were significant differences in SP rates between the SLE patients and healthy controls, respectively, for H1N1 (RR 0.79, 95% CI 0.73-0.87) and B strain (RR 0.75, 95% CI 0.65-0.87), but not for H3N2 (RR 0.84, 95% CI 0.68-1.03). Subgroup analyses demonstrated SLE patients with immunosuppressants, corticosteroids, azathioprine and prednisone had significantly lower SP rates, compared with healthy controls. SLE patients with nonadjuvanted H1N1 vaccine had significantly lower SP rate, compared with healthy controls. SLE patients were not associated with increased adverse events (RR 1.88, 95% CI 0.94-3.77).SLE generates immunogenicity differently, compared with healthy controls in pandemic H1N1 and B strains, but same in seasonal H3N2 strain. Nonadjuvant and special kind of immunosuppressive biologics can play an important role in SLE immunogenicity to flu vaccine. There is no significant difference in adverse event rates between SLE patients and healthy controls.
Neuzil, Kathleen M; Tsvetnitsky, Vadim; Nyari, Linda J; Bright, Rick A; Boslego, John W
The 2009 influenza A/H1N1 pandemic demonstrated that a pandemic influenza virus has the potential to spread more rapidly in today's highly interconnected world than in the past. While pandemic morbidity and mortality are likely to be greatest in low-resource countries, manufacturing capacity and access to influenza vaccines predominantly exist in countries with greater resources and infrastructure. Even with recently expanded manufacturing capacity, the number of doses available within a 6-month timeframe would be inadequate to fully immunize the global population if the decision to implement a global vaccination program were made today. Improved, affordable vaccines are needed to limit the consequences of a global influenza outbreak and protect low-resource populations. PATH's Influenza Vaccine Project is supporting a range of activities in collaboration with private- and public-sector partners to advance the development of promising influenza vaccines that can be accessible and affordable for people in low-resource countries.
... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for Influenza Vaccine AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice with Comment Period. SUMMARY: Under the National Childhood Vaccine...
de Vries, Rory D.; Rimmelzwaan, Guus F.
ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345
... Flu Vaccines Are Made Selecting Viruses for the Seasonal Influenza Vaccine Vaccine Effectiveness Selected Publications Vaccination Benefit Publications Vaccine Safety Flu Vaccine and People with Egg Allergies Guidelines for Flu Vaccination Good Health Habits Key ...
Hovden, Arnt-Ove; Cox, Rebecca Jane; Haaheim, Lars Reinhardt
Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record. Annual vaccination is therefore recommended for all individuals with serious medical conditions, like COPD, and protects the vaccinee against influenza illness and also against hospitalization and death. In COPD patients, influenza infection can lead to exacerbations resulting in reduced quality of life, hospitalization and death in the most severe cases. Although there is only limited literature on the use of influenza vaccination solely in COPD patients, there is clearly enough evidence to recommend annual vaccination in this group. This review will focus on influenza virus and prophylaxis with inactivated influenza vaccines in COPD patients and other “at risk” groups to reduce morbidity, save lives, and reduce health care costs. PMID:18229561
Brown, Derek S; Arnold, Sarah E; Asay, Garrett; Lorick, Suchita A; Cho, Bo-Hyun; Basurto-Davila, Ricardo; Messonnier, Mark L
The use of alternative venues beyond physician offices may help to increase rates of population influenza vaccination. Schools provide a logical setting for reaching children, but most school-located vaccination (SLV) efforts to date have been limited to local areas. The potential reach and acceptability of SLV at the national level is unknown in the United States. To address this gap, we conducted a nationally representative online survey of 1088 parents of school-aged children. We estimate rates of, and factors associated with, future hypothetical parental consent for children to participate in SLV for influenza. Based on logistic regression analysis, we estimate that 51% of parents would be willing to consent to SLV for influenza. Among those who would consent, SLV was reported as more convenient than the regular location (42.1% vs. 19.9%, P<0.001). However the regular location was preferred over SLV for the child's well-being in case of side effects (46.4% vs. 20.9%, P<0.001) and proper administration of the vaccine (31.0% vs. 21.0%, P<0.001). Parents with college degrees and whose child received the 2009-2010 seasonal or 2009 H1N1 influenza vaccination were more likely to consent, as were parents of uninsured children. Several measures of concern about vaccine safety were negatively associated with consent for SLV. Of those not against SLV, schools were preferred as more convenient to the regular location by college graduates, those whose child received the 2009-2010 seasonal or 2009 H1N1 influenza vaccination, and those with greater travel and clinic time. With an estimated one-half of U.S. parents willing to consent to SLV, this study shows the potential to use schools for large-scale influenza vaccination programs in the U.S.
Gendon, Iu Z
Published data related with comparison studies of safety, efficiency and some other properties of cold-adapted live influenza vaccine (LIV) and of inactivated influenza vaccine (IIV) are analyzed. LIV and IIV do not differ by systemic reactions after administration; however, it is not ruled out that there can be unfavorable reactions in vaccination of persons with allergy to the chicken-embryo proteins as well as in cases of persistence/reversion of cold-adapted strain observed in vaccination of persons with primary impairments of the immune system. There are no convincing data, up to now, on that LIV is superior to IIV in coping with influenza pandemics. The efficiency of LIV and IIV for children aged 3 years and more and for healthy adults is virtually identical. Additional controllable field comparative studies of LIV and IIV efficiency in immunization of elderly persons are needed. Limited data on LIV efficiency for children aged 2 months and more were obtained. The need in a 2-stage vaccination of all age group with the aim of ensuring responses to all 3 LIV components is, certainly, a LIV disadvantage. In case of IIV, the 2-stage vaccination is needed only for persons who were not ill with influenza. The intranasal LIV administration has, from the practical and psychological standpoints, an advantage before the IIV administration by syringe. The ability of LIV to protect from the drift influenza-virus variations could be its advantage before IIV; still, more research is needed to verify it. Transplantable cell lines meeting the WHO requirements could be an optimal substrate for the production of LIV and IIV. Children are the optimal age group for influenza prevention by cold-adapted LIV, whereas, IIV fits better for vaccination of adults and elderly persons.
Chen, Wilbur H.; Jackson, Lisa A.; Edwards, Kathryn M.; Keitel, Wendy A.; Hill, Heather; Noah, Diana L.; Creech, C. Buddy; Patel, Shital M.; Mangal, Brian; Kotloff, Karen L.
Background The national stockpile for influenza pandemic preparedness includes vaccines against an array of strains and adjuvants that could be utilized to induce immunologic priming as a pandemic wave emerges. We assessed the feasibility of a strategy that allows the flexibility of postmanufacture mixture of vaccine and adjuvant at the point of care. Methods We conducted a randomized, double-blind, multicenter trial among healthy adults aged 18–49 years who received 2 doses of inactivated influenza A/Indonesia/05/2005 (H5N1 clade 2.2.3) virus vaccine containing either 3.75, 7.5, or 15 µg of hemagglutinin (HA) with or without AS03 adjuvant, administered 21 days apart. Subjects were observed for local (injection site) and systemic reactogenicity and adverse events. Sera were tested for hemagglutination inhibition (HAI) and microneutralization (MN) antibody levels against the homologous strain and 4 heterologous avian strains. Results Vaccine containing ASO3 adjuvant was associated with significantly more local reactions compared with nonadjuvanted vaccine, but these were short-lived and resolved spontaneously. Although the immune response to nonadjuvanted vaccine was poor, 2 doses of AS03-adjuvanted vaccine containing as little as 3.75 µg of HA elicited robust immune responses resulting in seroprotective titers (≥1:40) to the homologous strain in ≥86% of subjects by HAI and in 95% of subjects by MN. Cross-clade antibody responses were also observed with AS03-adjuvanted vaccine, but not nonadjuvanted vaccine. Conclusions AS03 adjuvant formulated with inactivated vaccine at the administration site significantly enhanced the immune responses to H5N1 vaccine and has the potential to markedly improve vaccine responses and accelerate delivery during an influenza pandemic. Clinical Trials Registration NCT01317758. PMID:25734159
Naval Health Research Center Mid-Season Influenza Vaccine Effectiveness Estimates for the 2013–2014 Influenza Season Angelia A. Cost...2000–2013 P A G E 1 5 Brief report: mid-season influenza vaccine effectiveness estimates for the 2013–2014 influenza season Angelia A. Cost, PhD...Mid-Season Influenza Vaccine Effectiveness Estimates for the 2013–2014 Influenza Season Angelia A
Huber, Victor C
Vaccination against influenza represents our most effective form of prevention. Historical approaches toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic. Despite their effectiveness, these historical approaches do not allow for the incorporation of changes into the vaccine in a timely manner. In 2013, a recombinant protein-based vaccine that induces immunity toward the influenza virus hemagglutinin was approved for use in the USA. This vaccine represents the first approved vaccine formulation that does not require an influenza virus intermediate for production. This review presents a brief history of influenza vaccines, with insight into the potential future application of vaccines generated using recombinant technology.
Salleras, Luis; Navas, Encarna; Torner, Nuria; Prat, Andreu A.; Garrido, Patricio; Soldevila, Núria; Domínguez, Angela
The aim of this study was to systematically review published studies that evaluated the efficiency of inactivated influenza vaccination in preventing seasonal influenza in children. The vaccine evaluated was the influenza-inactivated vaccine in 10 studies and the virosomal inactivated vaccine in 3 studies. The results show that yearly vaccination of children with the inactivated influenza vaccine saves money from the societal and family perspectives but not from the public or private provider perspective. When vaccination does not save money, the cost-effectiveness ratios were very acceptable. It can be concluded, that inactivated influenza vaccination of children is a very efficient intervention. PMID:23295894
Kang, Kyuri; Han, Seunghoon; Hong, Taegon; Jeon, Sangil; Paek, Jeongki; Kang, Jin Han
Purpose A phase I clinical trial was conducted to evaluate the immunogenicity and safety of newly developed egg-cultivated trivalent inactivated split influenza vaccine (TIV) in Korea. Materials and Methods The TIV was administered to 43 healthy male adults. Subjects with high pre-existing titers were excluded in a screening step. Immune response was measured by a hemagglutination inhibition (HI) assay. Results The seroprotection rates against A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2009 were 74.42% [95% confidence interval (CI): 61.38–87.46], 72.09% (95% CI: 58.69–85.50), and 86.05% (95% CI: 75.69–96.40), respectively. Calculated seroconversion rates were 74.42% (95% CI: 61.38–87.46), 74.42% (95% CI: 61.38–87.46), and 79.07% (95% CI: 66.91–91.23), respectively. There were 25 episodes of solicited local adverse events in 21 subjects (47.73%), 21 episodes of solicited general adverse events in 16 subjects (36.36%) and 5 episodes of unsolicited adverse events in 5 subjects (11.36%). All adverse events were grade 1 or 2 and disappeared within three days. Conclusion The immunogenicity and safety of TIV established in this phase I trial are sufficient to plan a larger scale clinical trial. PMID:27593862
In this study we describe the sociodemographic characteristics of people participating in a clinical trial on the safety and immunogenicity of a H5N1 influenza vaccine and we identify the main motivations for joining it. PMID:22452976
On June 11, 2009 the World Health Organization (WHO) declared that the outbreaks caused by novel swine-origin influenza A (H1N1) virus had reached pandemic proportions. The pandemic H1N1 (H1N1pdm) is the predominant influenza strain in the human population. It has also crossed the species barriers a...
Araz, Ozgur M; Galvani, Alison; Meyers, Lauren A
Pandemic influenza is an international public health concern. In light of the persistent threat of H5N1 avian influenza and the recent pandemic of A/H1N1swine influenza outbreak, public health agencies around the globe are continuously revising their preparedness plans. The A/H1N1 pandemic of 2009 demonstrated that influenza activity and severity might vary considerably among age groups and locations, and the distribution of an effective influenza vaccine may be significantly delayed and staggered. Thus, pandemic influenza vaccine distribution policies should be tailored to the demographic and spatial structures of communities. Here, we introduce a bi-criteria decision-making framework for vaccine distribution policies that is based on a geospatial and demographically-structured model of pandemic influenza transmission within and between counties of Arizona in the Unites States. Based on data from the 2009-2010 H1N1 pandemic, the policy predicted to reduce overall attack rate most effectively is prioritizing counties expected to experience the latest epidemic waves (a policy that may be politically untenable). However, when we consider reductions in both the attack rate and the waiting period for those seeking vaccines, the widely adopted pro rata policy (distributing according to population size) is also predicted to be an effective strategy.
Zhang, Naru; Zheng, Bo-Jian; Lu, Lu; Zhou, Yusen; Jiang, Shibo; Du, Lanying
The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines. PMID:25529753
Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.
Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota
This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.
Coelingh, Kathleen L; Luke, Catherine J; Jin, Hong; Talaat, Kawsar R
Avian and animal influenza viruses can sporadically transmit to humans, causing outbreaks of varying severity. In some cases, further human-to-human virus transmission does not occur, and the outbreak in humans is limited. In other cases, sustained human-to-human transmission occurs, resulting in worldwide influenza pandemics. Preparation for future pandemics is an important global public health goal. A key objective of preparedness is to gain an understanding of how to design, test, and manufacture effective vaccines that could be stockpiled for use in a pandemic. This review summarizes results of an ongoing collaboration to produce, characterize, and clinically test a library of live attenuated influenza vaccine strains (based on Ann Arbor attenuated Type A strain) containing protective antigens from influenza viruses considered to be of high pandemic potential.
Park, Jae-Keun; Taubenberger, Jeffery K.
Influenza viruses are a significant public health threat, causing both annually circulating epidemics and unpredictable pandemics. Vaccination is the best means of control against individual cases of influenza and also for decreasing epidemic spread in the population. However, rapid influenza virus evolution requires continual reformulation of vaccines for annual influenza epidemics, and because pandemics cannot be accurately predicted, no current vaccine strategy can induce broad protection against all subtypes of influenza viruses. Recent work has suggested that such broadly protective, or “universal”, influenza virus vaccines might be achievable using vaccine strategies that target conserved B- and T-cell epitopes. PMID:26977452
Mossad, Sherif B
Influenza vaccination remains our best measure to prevent epidemic and pandemic influenza. We must continue to improve vaccination rates for targeted populations. Antiviral options are currently limited to the neuraminidase inhibitors.
Griffin, Marie R
Each year, an average of 5 to 10 percent of the U.S. population has symptomatic influenza illness, 226,000 persons are hospitalized and 24,000 die due to influenza-associated illness. Hospitalization rates are highest at the extremes of age, about one per 1,000 or higher in infants, persons age 65 and older and persons with chronic medical conditions. Ninety percent of deaths are in persons age 65 and older, but deaths also occur rarely in healthy children and young adults. Current influenza vaccines are moderately effective, with current evidence suggesting that they can prevent about half of influenza-associated symptomatic illness, outpatient visits, hospitalizations and deaths, with the evidence weaker for the most serious complications. Current licensed vaccines have mild immediate adverse effects and serious adverse effects are rare. Annual estimates of influenza vaccine effectiveness against the spectrum of clinical illness and in all age groups are needed to evaluate and support current vaccine policies and to help guide more effective vaccine development. Increased use of the current imperfect vaccines could prevent substantial morbidity and mortality in the U.S.
Suarez, David L
Vaccination for both low pathogenicity avian influenza and highly pathogenic avian influenza is commonly used by countries that have become endemic for avian influenza virus, but stamping-out policies are still common for countries with recently introduced disease. Stamping-out policies of euthanatizing infected and at-risk flocks has been an effective control tool, but it comes at a high social and economic cost. Efforts to identify alternative ways to respond to outbreaks without widespread stamping out has become a goal for organizations like the World Organisation for Animal Health. A major issue with vaccination for avian influenza is trade considerations because countries that vaccinate are often considered to be endemic for the disease and they typically lose their export markets. Primarily as a tool to promote trade, the concept of DIVA (differentiate infected from vaccinated animals) has been considered for avian influenza, but the goal for trade is to differentiate vaccinated and not-infected from vaccinated and infected animals because trading partners are unwilling to accept infected birds. Several different strategies have been investigated for a DIVA strategy, but each has advantages and disadvantages. A review of current knowledge on the research and implementation of the DIVA strategy will be discussed with possible ways to implement this strategy in the field. The increased desire for a workable DIVA strategy may lead to one of these ideas moving from the experimental to the practical.
Friede, M; Serdobova, I; Palkonyay, L; Kieny, M P
Increase of influenza vaccine production capacity in developing countries has been identified as an important element of global pandemic preparedness. Nevertheless, technology transfer for influenza vaccine production to developing country vaccine manufacturers has proven difficult because of lack of interested technology providers. As an alternative to an individual provider-recipient relationship, a technology and training platform (a "hub") for a generic non-proprietary process was established at a public sector European manufacturer's site. The conditions for setting up such a platform and the potential applicability of this model to other biologicals are discussed.
Davenport, F. M.
The history of the development of influenza virus vaccine is traced from its origin with experimental studies of influenza virus in ferrets and mice and the first trials in man. Knowledge of the basis of immunity to the viruses in experimental animals and in man has grown steadily over the years and has been essential to successful immunization. Virus variation affecting the surface antigens of the virus is seen as the principal obstacle to the application of vaccines in man. So significant are the changes occurring during antigenic drift that former concepts of a polyvalent vaccine cannot provide a solution of the problem of the composition of vaccines. Disrupted virus vaccines appear to provide the answer to the prevention of vaccine reactions. PMID:461277
Kattah, Nicole H.; Newell, Evan; Dekker, Cornelia L.; Davis, Mark M.; Utz, Paul J.
Background Existing methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. The development of highly multiplex proteomics platforms capable of capturing a high level of antibody binding information will enable researchers and clinicians to generate rapid and meaningful readouts of influenza-specific antibody reactivity. Methods We developed influenza hemagglutinin (HA) whole-protein and peptide microarrays and validated that the arrays allow detection of specific antibody reactivity across a broad dynamic range using commercially available antibodies targeted to linear and conformational HA epitopes. We derived serum from blood draws taken from 76 young and elderly subjects immediately before and 28±7 days post-vaccination with the 2008/2009 trivalent influenza vaccine and determined the antibody reactivity of these sera to influenza array antigens. Results Using linear regression and correcting for multiple hypothesis testing by the Benjamini and Hochberg method of permutations over 1000 resamplings, we identified antibody reactivity to influenza whole-protein and peptide array features that correlated significantly with age, H1N1, and B-strain post-vaccine titer as assessed through a standard microneutralization assay (p<0.05, q <0.2). Notably, we identified several peptide epitopes that were inversely correlated with regard to age and seasonal H1N1 and B-strain neutralization titer (p<0.05, q <0.2), implicating reactivity to these epitopes in age-related defects in response to H1N1 influenza. We also employed multivariate linear regression with cross-validation to build models based on age and pre-vaccine peptide reactivity that predicted vaccine-induced neutralization of seasonal H1N1 and H3N2 influenza strains with a high level of accuracy (84.7% and 74.0%, respectively). Conclusion Our methods provide powerful tools for rapid and accurate measurement of broad antibody-based immune
... Proclamation 8615--National Influenza Vaccination Week, 2010 #0; #0; #0; Presidential Documents #0; #0; #0;#0...;Title 3-- #0;The President ] Proclamation 8615 of December 7, 2010 National Influenza Vaccination Week... complications take American lives each year. During National Influenza Vaccination Week, we remind all...
Cooper, Curtis; Thorne, Anona
Clinical experience suggests Oculorespiratory Syndrome (ORS) following influenza vaccination is rare in HIV but this is not well evaluated. We assessed ORS incidence in a randomized influenza vaccine trial of HIV participants. The overall incidence was 0.8% suggesting that influenza vaccine ORS incidence is reduced in HIV.
Avian influenza (AI) vaccines have been developed and used to protect poultry and other birds in various countries of the world. Protection is principally mediated by an immune response to the subtype-specific hemagglutinin (HA) protein. AI vaccines prevent clinical signs of disease, death, egg pr...
Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna
The 2009 H1N1 influenza virus presented a major challenge to health departments, schools, and other community partners to effectively vaccinate large numbers of Americans, primarily children. The use of school-located vaccination (SLV) programs to address this challenge led health departments and schools to become creative in developing models for…
Ko, Hyun Sun; Jo, Yun Seong; Kim, Yeun Hee; Park, Yong-Gyu; Moon, Hee Bong; Lee, Young
Objective The aims of the present study were to investigate the women's perspective on influenza infection and vaccination and to evaluate how they influence vaccine acceptability, in Korean women of childbearing age. Methods This was a prospective study by random survey of women of childbearing age (20 to 45 years). They were asked to complete a questionnaire assessing their knowledge, attitudes and acceptability of influenza vaccination before and during pregnancy. This study utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES) between 2008 and 2012, to analyze the recent influenza vaccination trends. Results According to KNHANES (2008-2012), influenza vaccination rates in women of childbearing age have increased up to 26.4%, after 2009. The questionnaire was completed by 308 women. Vaccination rate during pregnancy or planning a pregnancy was 38.6%. The immunization rate increased significantly with the mean number of correct answers (P<0.001). Women who received influenza vaccination were more likely to be previously informed of the recommendations concerning the influenza vaccination before or during pregnancy, received the influenza vaccination in the past, and of the opinion that influenza vaccination is not dangerous during pregnancy, with odds ratios of 14.6 (95% confidence interval [CI], 6.44 to 33.33; P<0.0001), 3.6 (95% CI, 1.84 to 6.97; P=0.0002) and 2.7 (95% CI, 1.34 to 5.47; P=0.0057). Conclusion Influenza vaccination rate in women of childbearing age has increased in this study and national data. More information and recommendation by healthcare workers, especially obstetricians, including safety of vaccination, might be critical for improving vaccination rate in women of childbearing age. PMID:25798420
Uhart, Mathieu; Bricout, Hélène; Clay, Emilie; Largeron, Nathalie
ABSTRACT Influenza B strains represent on average 23% of all circulating strains in Europe and when there is a vaccine mismatch on B strains, additional influenza-related hospitalizations and deaths as well as substantial additional costs are observed. The objective was to estimate the public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines (QIV) compared to trivalent influenza vaccines (TIV) in Europe (EU). Based on data from 5 EU countries (France, Germany, Italy, Spain and UK) during 10 influenza seasons from 2002 to 2013, epidemiological and associated economic outcomes were estimated for each season for the actual scenario where the TIV was used, and for a hypothetical scenario where QIV could have been used instead. By using QIV, this study estimated that for the 5 EU countries, an additional 1.03 million (327.9/100,000 inhabitants) influenza cases, 453,000 (143.9/100,000) general practitioners consultations, 672,000 (213.1/100,000) workdays lost, 24,000 (7.7/100,000) hospitalizations and 10,000 (3.1/100,000) deaths could have been avoided compared to the use of TIV over the 10-seasons-period. This study estimates that QIV can be of economic value since from a societal perspective 15 million Euros would have been saved on general practitioners consultations (14 million Euros from third-party payer perspective), 77 million on hospitalizations (74 million Euros from third-party payer perspective) and 150 million Euros on workdays lost, across the 5 EU countries. In conclusion, the present study estimates that, compared to TIV, QIV may result in a substantial decrease in epidemiological burden and in influenza-related costs. PMID:27166916
Bicho, Diana; Queiroz, João António; Tomaz, Cândida Teixeira
Current influenza vaccines have long been used to fight flu infectious; however, recent advances highlight the importance of produce new alternatives. Even though traditional influenza vaccines are safe and usually effective, they need to be uploaded every year to anticipate circulating flu viruses. This limitation together with the use of embryonated chicken eggs as the substrate for vaccine production, is time-consuming and could involve potential biohazards in growth of new virus strains. Plasmid DNA produced by prokaryote microorganisms and encoding foreign proteins had emerged as a promising therapeutic tool. This technology allows the expression of a gene of interest by eukaryotic cells in order to induce protective immune responses against the pathogen of interest. In this review, we discuss the strategies to choose the best DNA vaccine to be applied in the treatment and prevention of influenza. Specifically, we give an update of influenza DNA vaccines developments, all involved techniques, their main characteristics, applicability and technical features to obtain the best option against influenza infections.
Kumar, Supriya; Quinn, Sandra Crouse; Kim, Kevin H.; Musa, Donald; Hilyard, Karen M.; Freimuth, Vicki S.
Research on influenza vaccine uptake has focused largely on intrapersonal determinants (perceived risk, past vaccine acceptance, perceived vaccine safety) and on physician recommendation. The authors used a social ecological framework to examine influenza vaccine uptake during the 2009 H1N1 pandemic. Surveying an adult population (n = 2,079) in…
... Influenza Vaccination Subgroup's Draft Report and Draft Recommendations for Achieving the Healthy People 2020 Annual Coverage Goals for Influenza Vaccination in Healthcare Personnel AGENCY: National Vaccine... of the National Vaccine Advisory Committee (NVAC), Healthcare Personnel Influenza...
Brady, Rebecca C.; Treanor, John J.; Atmar, Robert L.; Keitel, Wendy A.; Edelman, Robert; Chen, Wilbur H.; Winokur, Patricia; Belshe, Robert; Graham, Irene L.; Noah, Diana Lee; Guo, Kuo; Hill, Heather
A total of 600 healthy adults ≥ 65 years were randomized to receive 2 vaccinations 1 month apart of a subvirion avian influenza A/H5N1 vaccine containing 3.75, 7.5, 15, or 45 μg of hemagglutinin (HA) with or without aluminum hydroxide (AlOH). All formulations were safe. Groups given the vaccine with AlOH had more injection site discomfort. Dose-related increases in antibody responses were noted after the second vaccination. Antibody responses to the vaccine were not enhanced by AlOH at any HA dose level. A microneutralization titer ≥ 40 was observed in 36% and 40% of subjects who received 45 μg of HA with or without AlOH, respectively. PMID:19577636
Smith, D.J.; Ackley, D.H.; Forrest, S.; Perelson, A.S.
Although influenza vaccine efficacy is 70--90% in young healthy first-time vaccinees, the efficacy in repeat vaccinees has varied considerably. In some studies, vaccine efficacy in repeat vaccinees was higher than in first-time vaccinees, whereas in other studies vaccine efficacy in repeat vaccinees was significantly lower than in first-time vaccinees and sometimes no higher than in unvaccinated controls. It is known that the closeness of the antigenic match between the vaccine strain and the epidemic virus is important for vaccine effectiveness. In this study the authors show that the antigenic differences between a first vaccine strain and a second vaccine strain, and between the first vaccine strain and the epidemic strain, might account for the observed variation in attack rate among two-time vaccinees.
Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination
Díez-Domingo, Javier; Baldó, José-María; Planelles-Catarino, Maria Victoria; Garcés-Sánchez, María; Ubeda, Isabel; Jubert–Rosich, Angels; Marès, Josep; Garcia-Corbeira, Pilar; Moris, Philippe; Teko, Maurice; Vanden Abeele, Carline; Gillard, Paul
Background An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3–9 years. Methods In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3–9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03A or AS03B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. (NCT00502593). Results The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4+ T cells with a TH1 profile were observed. Conclusions Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination. PMID:25652873
Stowe, Julia; Andrews, Nick; Wise, Lesley; Miller, Elizabeth
Concern about a possible increased risk of Bell's palsy after parenteral inactivated influenza vaccine was raised following the publication in 2004 of a Swiss study in which there was an increased risk following the nasal inactivated formulation of the vaccine. When data from passive reporting systems in the United States and the United Kingdom were examined there was some evidence of increased reporting following the parenteral vaccine. A large population based study using the General Practice Research Database (GPRD) was therefore performed to test the hypothesis that there was an increased risk of Bell's palsy in the three months following parenteral inactivated influenza vaccine. The risk was also assessed for the same period following pneumococcal vaccine and was stratified into three age groups (<45, 45-64 and 65+ years). Relative incidence (RI) estimates were calculated using the self-controlled case-series method and showed no evidence of an increased risk in the three months following parenteral inactivated influenza vaccine RI 0.92 (95% confidence interval 0.78-1.08). There was also no evidence of an increased risk in any age group or following pneumococcal vaccine. A significant increase was seen on the day of vaccination (day 0) probably due to opportunistic recording of cases.
Lind, Candace; Russell, Margaret L.; MacDonald, Judy; Collins, Ramona; Frank, Christine J.; Davis, Amy E.
Background School-age children are important drivers of annual influenza epidemics yet influenza vaccination coverage of this population is low despite universal publicly funded influenza vaccination in Alberta, Canada. Immunizing children at school may potentially increase vaccine uptake. As parents are a key stakeholder group for such a program, it is important to consider their concerns. Purpose We explored parents’ perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools, and obtained suggestions for structuring such a program. Participants Forty-eight parents of children aged 5-18 years participated in 9 focus groups. Participants lived in urban areas of the Alberta Health Services Calgary Zone. Findings Three major themes emerged: Advantages of school-based influenza vaccination (SBIV), Disadvantages of SBIV, and Implications for program design & delivery. Advantages were perceived to occur for different populations: children (e.g. emotional support), families (e.g. convenience), the community (e.g. benefits for school and multicultural communities), the health sector (e.g. reductions in costs due to burden of illness) and to society at large (e.g. indirect conduit of information about health services, building structure for pandemic preparedness, building healthy lifestyles). Disadvantages, however, might also occur for children (e.g. older children less likely to be immunized), families (e.g. communication challenges, perceived loss of parental control over information, choices and decisions) and the education sector (loss of instructional time). Nine second-level themes emerged within the major theme of Implications for program design & delivery: program goals/objectives, consent process, stakeholder consultation, age-appropriate program, education, communication, logistics, immunizing agent, and clinic process. Conclusions Parents perceived advantages and
Håberg, Siri E; Trogstad, Lill; Gunnes, Nina; Wilcox, Allen J.; Gjessing, Håkon K.; Samuelsen, Sven Ove; Skrondal, Anders; Cappelen, Inger; Engeland, Anders; Aavitsland, Preben; Madsen, Steinar; Buajordet, Ingebjørg; Furu, Kari; Nafstad, Per; Vollset, Stein Emil; Berit, Feiring; Nøkleby, Hanne; Magnus, Per; Stoltenberg, Camilla
Background During the 2009 influenza pandemic, pregnant women were at particular risk of serious influenza illness. This concern was further complicated by questions about vaccine safety in pregnant women raised by anecdotal reports of fetal deaths following vaccination. Methods We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios of fetal death, with gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables. Results There were 117,347 eligible pregnancies in Norway in 2009–2010. Fetal mortality was 4.9/1000. 54% of pregnant women in their second or third trimester during the pandemic were vaccinated. Vaccination in pregnancy substantially reduced the risk of influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). A clinical diagnosis of influenza in the mother increased the risk of fetal death (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). Among pregnant women, the risk of fetal death was lower with vaccination, although this reduction was not statistically significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17). Conclusions Pandemic influenza in pregnancy was associated with increased risk of fetal death. Vaccination during pregnancy reduced the risk of influenza diagnosis. Vaccination itself did not increase fetal mortality, and may have reduced the risk of influenza-related fetal death during the pandemic. PMID:23323868
Madan, Anuradha; Segall, Nathan; Ferguson, Murdo; Frenette, Louise; Kroll, Robin; Friel, Damien; Soni, Jyoti; Li, Ping; Innis, Bruce L.; Schuind, Anne
Background. Almost 700 cases of human infection with avian influenza A/H7N9 have been reported since 2013. Pandemic preparedness strategies include H7N9 vaccine development. Methods. We evaluated an inactivated H7N9 vaccine in an observer-blind study in healthy adults aged 18–64 years. Participants (420) were randomized to receive 1 of 4 AS03-adjuvanted vaccines (low or medium dose of hemagglutinin with AS03A or AS03B), one nonadjuvanted vaccine, or placebo. The coprimary immunogenicity objective determined whether adjuvanted vaccines elicited an immune response against the vaccine-homologous virus, 21 days after the second vaccine dose per US and European licensure criteria in the per-protocol cohort (n = 389). Results. All adjuvanted vaccines met regulatory acceptance criteria. In groups receiving adjuvanted formulations, seroconversion rates were ≥85.7%, seroprotection rates ≥91.1%, and geometric mean titers ≥92.9% versus 23.2%, 28.6%, and 17.2 for the nonadjuvanted vaccine. The AS03 adjuvant enhanced immune response at antigen-sparing doses. Injection site pain occurred more frequently with adjuvanted vaccines (in ≤98.3% of vaccinees) than with the nonadjuvanted vaccine (40.7%) or placebo (20.0%). None of the 20 serious adverse events reported were related to vaccination. Conclusions. Two doses of AS03-adjuvanted H7N9 vaccine were well tolerated and induced a robust antibody response at antigen-sparing doses in healthy adults. Clinical Trials Registration. NCT01999842. PMID:27609809
Tabynov, Kaissar; Yespembetov, Bolat; Matikhan, Nurali; Ryskeldinova, Sholpan; Zinina, Nadezhda; Kydyrbayev, Zhailaubay; Assanzhanova, Nurika; Tabynov, Kairat; Renukaradhya, Gourapura J; Mukhitdinova, Gulnara; Sansyzbay, Abylai
Previously we developed and evaluated a candidate influenza viral vector based Brucella abortus vaccine (Flu-BA) administered with a potent adjuvant Montanide Gel01 in cattle, which was found safe and highly effective. This study was aimed to establish a proof-of-concept of the efficacy of Flu-BA vaccine formulation in sheep and goats. We vaccinated sheep and goats with Flu-BA vaccine and as a positive control vaccinated a group of animals with a commercial B. melitensis Rev.1 vaccine. Clinically, both Flu-BA and Rev.1 vaccines were found safe. Serological analysis showed the animals received Flu-BA vaccine did not induce antibody response against Brucella Omp16 and L7/L12 proteins during the period of our study (56days post-initial vaccination, PIV). But observed significant antigen-specific T cell response indicated by increased lymphocyte stimulation index and enhanced secretion of IFN-γ at day 56 PIV in Flu-BA group. The Flu-BA vaccinated animals completely protected 57.1% of sheep and 42.9% of goats against B. melitensis 16M challenge. The severity of brucellosis in terms of infection index and colonization of Brucella in tissues was significantly lower in the Flu-BA group compared to negative control animals group. Nevertheless, positive control commercial Rev.1 vaccine provided strong antigen-specific T cell immunity and protection against B. melitensis 16M infection. We conclude that the Flu-BA vaccine induces a significant antigen-specific T-cell response and provides complete protection in approximately 50% of sheep and goats against B. melitensis 16M infection. Further investigations are needed to improve the efficacy of Flu-BA and explore its practical application in small ruminants.
Taylor, Eric G.; Atkins, Katherine E.; Chapman, Gretchen B.; Galvani, Alison P.
Objective Americans do not vaccinate nearly enough against Influenza (flu) infection, despite severe health and economic burden of influenza. Younger people are disproportionately responsible for transmission, but do not suffer severely from the flu. Thus, to achieve herd immunity, prosocial motivation needs to be a partial driver of vaccination decisions. Past research has not established the causal role of prosociality in flu vaccination, and the current research evaluates such causal relationship by experimentally eliciting prosociality through messages about flu victims. Methods In an experimental study, we described potential flu victims who would suffer from the decision of others to not vaccinate to 3952 Internet participants across eight countries. We measured sympathy, general prosociality, and vaccination intentions. The study included two identifiable victim conditions (one with an elderly victim and another with a young victim), an unidentified victim condition, and a no message condition. Results We found that any of the three messages increased flu vaccination intentions. Moreover, this effect was mediated by enhanced prosocial motives, and was stronger among people who were historical non-vaccinators. In addition, younger victim elicited greater sympathy, and describing identifiable victims increased general sympathy and prosocial motives. Conclusions These findings provide direct experimental evidence on the causal role of prosocial motives in flu vaccination, by showing that people can be prompted to vaccinate for the sake of benefiting others. PMID:27459237
Plasai, Valaikanya; Lertmaharit, Somrat; Viputsiri, Ong-Arj; Pongpanich, Sathirakorn; Panichpathompong, Usa; Tarnmaneewongse, Veerachai; Baron-Papillon, Florence; Cheunkitmongkol, Sunate
This study aimed to determine the effectiveness of influenza vaccinations among the elderly in Bangkok in reducing influenza-like illness (ILI) and influenza-related complications. Using a non-randomized, controlled, prospective methodology, healthy, active people aged 60 years or more, living in the Bangkok Metropolitan Administration (BMA) area, were studied. The two study cohorts comprised 519 persons in the vaccinated group and 520 in the non-vaccinated group. The outcome under study was influenza-like illness (ILI), as reported by the study volunteers. The two groups were comparable for most socio-demographic characteristics, except for gender, level of education, marital status, and smoking habit. The age range was 60-88 years (mean: 68 years). Females outnumbered males in both groups, with ratio of female to male of 2.6:1 and 1.9:1 in the vaccinated and non-vaccinated groups, respectively. The top three co-morbidities among these groups were hypertension, diabetes mellitus, and heart disease, in that order. Only 1% of the volunteers reported lung disease as co-morbidity. During the 12-month study period, a total of 107 volunteers reported ILI in both groups, with 38 persons in the vaccinated group and 69 persons in the non-vaccinated group. There were 46 ILI episodes in the vaccinated group, and 86 in the non-vaccinated group, for a total of 132 episodes. The incidence rates rates of influenza in this population, therefore, were 8.9% for the vaccinated and 16.9% for the non-vaccinated groups; with a reduction in the rate of reported ILI and doctor visits of 8%. Vaccine effectiveness was rated at 47.6%, crude risk ratio at 1.9 (1.33-2.75), and adjusted risk ratio at 1.92 (95% CI: 1.25-2.95), after adjustment for gender, marital status, education, and smoking habit. No complications due to ILI were observed in this population during the study period. Hospitalizations during this period were due to non-ILI related causes, such as cancer and accident.
Shono, Aiko; Kondo, Masahide
In Japan, trivalent inactivated influenza vaccine is the only approved influenza vaccine. It is typically administrated by hypodermic injection, and children under 13 years of age are recommended to be vaccinated two times during each winter season. Live-attenuated influenza vaccine (LAIV) is administered by a thimerosal-free nasal spray. If LAIV is approved in the future in Japan, parents will have an alternative type of influenza vaccine for their children. This study investigated parents' preference for the type of seasonal influenza vaccine for their children if alternatives are available. The marginal willingness to pay for vaccine benefits was also evaluated. We conducted a discrete choice experiment, a quantitative approach that is often used in healthcare studies, in January 2013. Respondents were recruited from a registered online survey panel, and parents with at least one child under 13 years of age were offered questionnaires. This study showed that for seasonal influenza vaccines for their children, parents are more likely to value safety, including thimerosal-free vaccines and those with a lower risk of adverse events, instead of avoiding the momentary pain from an injection. If LAIV is released in Japan, the fact that it is thimerosal-free could be an advantage. However, for parents to choose LAIV, they would need to accept the slightly higher risk of minor adverse events from LAIV.
A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers
Quiambao, Beatriz; Van Der Meeren, Olivier; Kolhe, Devayani; Gatchalian, Salvacion
As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted. This study is registered at www.clinicaltrials.gov NCT number: NCT01106092 PMID:22330958
A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers.
Quiambao, Beatriz; Van Der Meeren, Olivier; Kolhe, Devayani; Gatchalian, Salvacion
As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted. This study is registered at www.clinicaltrials.gov NCT number: NCT01106092.
Icardi, Giancarlo; Orsi, Andrea; Ceravolo, Antonella; Ansaldi, Filippo
Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability. Data from clinical trials performed in children, adults <60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination. PMID:22293531
Weber, David J; Orenstein, Walter; Rutala, William A
Influenza causes substantial morbidity and mortality worldwide each year. Healthcare-associated influenza is a frequent event. Health care personnel (HCP) may be the source for infecting patients and may propagate nosocomial outbreaks. All HCP should receive a dose of influenza vaccine each year to protect themselves and others. This commentary will discuss the study recently published in the IJHPR by Nutman and Yoeli which assessed the beliefs and attitudes of HCP in an Israel hospital regarding influenza and the influenza vaccine. Unfortunately, as noted by Nutman and Yoeli in this issue many HCP in Israel choose not to receive influenza immunization and many harbor misconceptions regarding their risk for influenza as well as the benefits of influenza vaccine. We also discuss proven methods to increase acceptance by HCP for receiving an annual influenza vaccine.
Buckland, Barry C
The development and manufacture of an Influenza vaccine is unlike any other product in the Vaccine industry because of the need to change composition on a yearly basis. The poor efficacy of Influenza vaccines over the past 2 y in the Northern Hemisphere invites questions on how the vaccines are manufactured and how change in vaccine composition is controlled. The opinion expressed in this commentary is that the risk of not making the correct HA protein is increased by the need to adapt the new seasonal virus for good propagation in embryonated chicken eggs. This adaptation is required because not enough doses can be made in time for the new 'flu season unless productivity is reasonable. This problem is not necessarily solved by going to a cell culture host for virus propagation and that may explain why this more advanced technology approach is not more widely used. A vaccine based on hemagglutinin (HA) protein that does not involve Influenza virus propagation (such as Flublok®) side steps this particular problem. The exact HA sequence can be used as is in the virus. The technology can be run at large scale, already at 2 × 21,000L in Japan, in contrast to eggs where scale-up is by multiplication; the HA product is highly purified and made consistently in the form of rosettes. PMID:25844949
Tamura, Shin-Ichi; Ainai, Akira; Suzuki, Tadaki; Kurata, Takeshi; Hasegawa, Hideki
Influenza is a contagious, acute respiratory disease caused by the influenza virus. The mucosal lining in the host respiratory tract is not only the site of virus infection, but also the site of defense; it is at this site that the host immune response targets the virus and protects against reinfection. One of the most effective methods to prevent influenza is to induce specific antibody (Ab) responses in the respiratory tract by vaccination. Two types of influenza vaccines, intranasal live attenuated influenza virus (LAIV) vaccines and parenteral (injectable) inactivated vaccines, are currently used worldwide. These vaccines are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration. Live attenuated vaccines induce both secretory IgA (S-IgA) and serum IgG antibodies (Abs), whereas parenteral vaccines induce only serum IgG Abs. However, intranasal administration of inactivated vaccines together with an appropriate adjuvant induces both S-IgA and IgG Abs. Several preclinical studies on adjuvant-combined, nasal-inactivated vaccines revealed that nasal S-IgA Abs, a major immune component in the upper respiratory tract, reacted with homologous virus hemagglutinin (HA) and were highly cross-reactive with viral HA variants, resulting in protection and cross-protection against infection by both homologous and variant viruses, respectively. Serum-derived IgG Abs, which are present mainly in the lower respiratory tract, are less cross-reactive and cross-protective. In addition, our own clinical trials have shown that nasal-inactivated whole virus vaccines, including a built-in adjuvant (single-stranded RNA), induced serum hemagglutination inhibition (HI) Ab titers that fulfilled the EMA criteria for vaccine efficacy. The nasal-inactivated whole virus vaccines also induced high levels of nasal HI and neutralizing Ab titers, although we have not yet evaluated the nasal HI titers due to the lack of official criteria to establish efficacy based
Rinderknecht, Stephen; Bryant, Kristina; Nolan, Terry; Pavia-Ruz, Noris; Doniz, Carlos Aranza; Weber, Miguel Angel Rodriguez; Cohen, Christopher; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline M.
The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8,500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12–15 mo of age in two primary vaccination and two fourth dose phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p value < 0.05). There were no statistically significant differences between groups in the incidences of SAEs, NOCDs, rash, or AEs leading to ER visits, with the exceptions of anemia and viral gastroenteritis, which occurred significantly less frequently in those receiving HibMenCY than those receiving commercially available Hib vaccines. In this pooled safety analysis, the safety profile of HibMenCY was similar to the safety profile of licensed monovalent Hib vaccines, despite the addition of meningococcal antigens. These studies are registered at www.clinicaltrials.gov NCT00345579 (primary vaccination study), NCT00345683 (fourth dose vaccination study) and NCT00289783 (primary and fourth dose vaccination studies) PMID:22327493
Mooney, Alaina J; Tompkins, S Mark
Influenza A viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. While the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. Thus, there is need of improved influenza vaccines and vaccination strategies. This review discusses advances in alternative influenza vaccines, touching briefly on licensed vaccines and vaccine antigens; then reviewing recombinant subunit vaccines, virus-like particle vaccines and DNA vaccines, with the main focus on virus-vectored vaccine approaches. PMID:23440999
Safety and immunogenocity of a novel combined Haemophilus influenzae type b–Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old
Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai
A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6–23 months and in a single dose to children aged 2–5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6–23 months was 46.8% and that in vaccinees aged 2–5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases. PMID:25833163
Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old.
Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai
A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.
Prior to 2003, vaccines against avian influenza (AI) had limited, individual country or regional use in poultry. In late 2003, H5N1 high pathogenicity (HP) AI spread from China to multiple Southeast Asian countries, and to Europe during 2005 and Africa during 2006, challenging governments and all p...
Nakayama, Tetsuo; Kumagai, Takuji; Nishimura, Naoko; Ozaki, Takao; Okafuji, Teruo; Suzuki, Eitaro; Miyata, Akiko; Okada, Kenji; Ihara, Toshiaki
Although anaphylaxis is an extremely rare vaccine-associated adverse event, it occurred in young children following administration of the 2011/12 seasonal split influenza vaccine, which contained 2-phenoxyethanol as the preservative. These children had high levels of IgE antibodies against influenza vaccine components. We herein investigated why these children were sensitized. One hundred and seventeen series of serum samples were obtained immediately before, and one month after the first and second immunizations with the HA split vaccine of 2011/12. Forty-two sequential serum samples were collected in the acute and convalescent phases (2 and 4 weeks) after natural infection with H1N1 Pdm in 2009. IgE antibodies developed following the vaccination of young children with seasonal split vaccines, whereas no significant IgE response was observed following natural infection with H1N1 Pdm 2009. The prevalence of IgE antibodies was not influenced by outbreaks of H1N1 Pdm. Repeated immunization with the HA split vaccine induced IgE sensitization against the influenza vaccine irrespective of the H1N1, H3N2, or B influenza subtypes. The reasons why anaphylaxis only occurred in recipients of the influenza vaccine containing 2-phenoxyethanol are still being investigated, and the size distribution of antigen particles may have shifted to a slightly larger size. Since the fundamental reason was IgE sensitization, current split formulation for the seasonal influenza vaccine needs to be reconsidered to prevent the induction of IgE sensitization.
controlled studies. Vaccine 2012; 30:886–92. 11. Piedra PA, Gaglani MJ, Kozinetz CA, et al. Trivalent live attenuated intranasal influenza vaccine...120:e553–64. 12. Halloran ME, Piedra PA, Longini IM Jr, et al. Efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza A (Fujian
Nannei, Claudia; Chadwick, Christopher; Fatima, Hiba; Goldin, Shoshanna; Grubo, Myriam; Ganim, Alexandra
Through its Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) in collaboration with the United States Department of Health and Human Services has produced a checklist to support policy-makers and influenza vaccine manufacturers in identifying key technological, political, financial, and logistical issues affecting the sustainability of influenza vaccine production. This checklist highlights actions in five key areas that are beneficial for establishing successful local vaccine manufacturing. These five areas comprise: (1) the policy environment and health-care systems; (2) surveillance systems and influenza evidence; (3) product development and manufacturing; (4) product approval and regulation; and (5) communication to support influenza vaccination. Incorporating the checklist into national vaccine production programmes has identified the policy gaps and next steps for countries involved in GAP's Technology Transfer Initiative. Lessons learnt from country experiences provide context and insight that complement the checklist's goal of simplifying the complexities of influenza prevention, preparedness, and vaccine manufacturing.
Castella, A; Argentero, P A; Lanszweert, A
Despite recommendations, influenza vaccination coverage in health professionals remains low throughout the world. In order to identify reasons for adherence or refusal we conducted a study within our hospital by means of interview questionnaires which were distributed to health care workers to reveal factors influencing acceptance or refusal of vaccination and to get suggestions to improve vaccination coverage. There is good overlap between our results and data obtainable from international literature: the main motivating factor for vaccination is personal protection against influenza, while only a significantly smaller part gave protection of patients as a reason. The main factors for not adhering to vaccination are belief the vaccine is not effective, influenza-related sick leave, fear of adverse effects and lack of availability. These data point out the need for more information concerning the importance of influenza infection within risk groups, the safety and effectiveness of the vaccine. Further, it is suitable to increase availability of the vaccine free of charge.
Nogales, Aitor; Martínez-Sobrido, Luis
Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504
Yusibov, Vidadi; Kushnir, Natasha; Streatfield, Stephen J
Influenza infections continue to present a major threat to public health. Traditional modes of influenza vaccine manufacturing are failing to satisfy the global demand because of limited scalability and long production timelines. In contrast, subunit vaccines (SUVs) can be produced in heterologous expression systems in shorter times and at higher quantities. Plants are emerging as a promising platform for SUV production due to time efficiency, scalability, lack of harbored mammalian pathogens and possession of the machinery for eukaryotic post-translational protein modifications. So far, several organizations have utilized plant-based transient expression systems to produce SUVs against influenza, including vaccines based on virus-like particles. Plant-produced influenza SUV candidates have been extensively evaluated in animal models and some have shown safety and immunogenicity in clinical trials. Here, the authors review ongoing efforts and challenges to producing influenza SUV candidates in plants and discuss the likelihood of bringing these products to the market.
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.
Kang, Gloria J; Culp, Rachel K; Abbas, Kaja M
The study objective was to identify facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination in the United States. In 2009, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention expanded their recommendations for influenza vaccination to include school-aged children. We conducted a systematic review of studies focused on facilitators and barriers of parental attitudes toward school-located influenza vaccination in the United States from 1990 to 2016. We reviewed 11 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Facilitators were free/low cost vaccination; having belief in vaccine efficacy, influenza severity, and susceptibility; belief that vaccination is beneficial, important, and a social norm; perception of school setting advantages; trust; and parental presence. Barriers were cost; concerns regarding vaccine safety, efficacy, equipment sterility, and adverse effects; perception of school setting barriers; negative physician advice of contraindications; distrust in vaccines and school-located vaccination programs; and health information privacy concerns. We identified the facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination to assist in the evidence-based design and implementation of influenza vaccination programs targeted for children in the United States and to improve influenza vaccination coverage for population-wide health benefits.
Principi, Nicola; Senatore, Laura; Esposito, Susanna
Influenza is a very common disease among infants and young children, with a considerable clinical and socioeconomic impact. A significant number of health authorities presently recommend universal influenza vaccination for the pediatric population, but a large number of European health authorities is still reluctant to include influenza vaccination in their national vaccination programs. The reasons for this reluctance include the fact that the protection offered by the currently available vaccines is considered poor. This review shows that although future research could lead to an increase in the immunogenicity and potential efficacy of influenza vaccines, the available vaccines, even with their limits, assure sufficient protection in most subjects aged ≥ 6 months, thus reducing the total burden of influenza in young children and justifying the recommendation for the universal vaccination of the whole pediatric population. For younger subjects, the vaccination of their mother during pregnancy represents an efficacious strategy. PMID:26090704
Kerr, Stephen; Van Bennekom, Carla M; Mitchell, Allen A
Seasonal influenza vaccine is recommended for all pregnant women because of their increased risk for influenza-associated complications. In addition, receipt of influenza vaccine by women during pregnancy has been shown to protect their infants for several months after birth (1). As part of its case-control surveillance study of medications and birth defects, the Birth Defects Study of the Slone Epidemiology Center at Boston University has recorded data on vaccinations received during pregnancy since the 2005-06 influenza vaccination season. Among the 5,318 mothers of infants without major structural birth defects (control newborns) in this population, seasonal influenza vaccination coverage was approximately 20% in the seasons preceding the 2009-10 pandemic H1N1 (pH1N1) influenza season. During the 2009-10 influenza vaccination season, influenza vaccination coverage among pregnant women increased to 33%, and has increased modestly since then, to 41% during the 2013-14 season. Among pregnant women who received influenza vaccine during the 2013-14 season, 80% reported receiving their vaccine in a traditional health care setting, (e.g., the office of their obstetrician or primary care physician or their prenatal clinic) and 20% received it in a work/school, pharmacy/supermarket, or government setting. Incorporating routine administration of seasonal influenza vaccination into the management of pregnant women by their health care providers might increase coverage with this important public health intervention.
Although little has changed in vaccine technology for avian influenza virus (AIV) in the past 20 years, the approach to vaccination of poultry (chickens, turkeys and ducks) for avian influenza has evolved as highly pathogenic (HP) AIV has become endemic in several regions of the world. Vaccination f...
Avian influenza vaccines for poultry are based on hemagglutinin proteins and protection is specific to the vaccine subtype. Over 113 billion doses have been used between 2002 and 2010 for high pathogenicity avian influenza control. No universal vaccines are currently available. The majority of avian...
Huu, Tran Ngoc; Phuong, Nguyen Thi Minh; Toan, Nguyen Trong; Thang, Ho Vinh
Vietnam plans to replace the routine childhood diphtheria, pertussis and tetanus combination (DPT) vaccine with a pentavalent vaccine. The present study was performed to assess the immunogenicity and safety of the combined diphtheria, tetanus, whole-cell pertussis, hepatitis B (HepB), and Haemophilus influenzae type b (Hib) (DTwP-HepB-Hib) Quinvaxem® vaccine in children. A total of 131 infants received the Quinvaxem® vaccine at 2, 3 and 4 months. Antibody levels were measured at baseline, at one month after the third injection and one year after the first injection. Seroprotection rates were high for each vaccine antigen at one month after the third dose: 93.1% for diphtheria, 98.5% for tetanus, 99.2% for pertussis (seroconversion rate), 93.1% for HepB, and 100% for Hib (anti-PRP ≥ 0.15 µg/ml). The rate of children with protective antibodies persisting at one year after the first dose was 88.4% for diphtheria, 49.6% for pertussis, 82.2% for tetanus, 76.7% for HepB and 97.7% for Hib (anti-PRP ≥ 0.15 µg/ml). The Quinvaxem® vaccine was well tolerated and has a low rate of adverse events. Quinvaxem® given at 2, 3 and 4 months of age was immunogenic and safe for primary immunization among infants in Vietnam.
Steelfisher, Gillian K; Blendon, Robert J; Bekheit, Mark M; Mitchell, Elizabeth W; Williams, Jennifer; Lubell, Keri; Peugh, Jordon; DiSogra, Charles A
We sought to examine motivators and barriers related to monovalent 2009 influenza A (H1N1) vaccination among pregnant women. We conducted a national poll of pregnant women using a random online sample (237) and opt-in supplement (277). In all, 42% of pregnant women reported getting the vaccine. Vaccination was positively associated with attitudinal factors including believing the vaccine is very safe or benefits the baby, and with provider recommendations. Women in racial/ethnic minority groups, women with less education, and women <35 years were less likely to get the vaccine and had differing views and experiences. Despite H1N1 vaccination rates that are higher than past seasonal influenza rates, barriers like safety concerns may persist in a pandemic. Messaging from providers that encourages women to believe the vaccine is very safe and benefits their baby may be compelling. Messaging and outreach during future pandemics may require customization to increase vaccination among high-risk groups.
Pérez-Romero, P; Bulnes-Ramos, A; Torre-Cisneros, J; Gavaldá, J; Aydillo, T A; Moreno, A; Montejo, M; Fariñas, M C; Carratalá, J; Muñoz, P; Blanes, M; Fortún, J; Suárez-Benjumea, A; López-Medrano, F; Barranco, J L; Peghin, M; Roca, C; Lara, R; Cordero, E
Preventing influenza infection early after transplantation is essential, given the disease's high mortality. A multicentre prospective cohort study in adult solid organ transplant recipients (SOTR) receiving the influenza vaccine during four consecutive influenza seasons (2009-2013) was performed to assess the immunogenicity and safety of influenza vaccination in SOTR before and 6 months after transplantation. A total of 798 SOTR, 130 of them vaccinated within 6 months of transplantation and 668 of them vaccinated more than 6 months since transplantation. Seroprotection was similar in both groups: 73.1% vs. 76.5% for A/(H1N1)pdm (p 0.49), 67.5% vs. 74.1% for A/H3N2 (p 0.17) and 84.2% vs. 85.2% for influenza B (p 0.80), respectively. Geometric mean titres after vaccination did not differ among groups: 117.32 (95% confidence interval (CI) 81.52, 168.83) vs. 87.43 (95% CI 72.87, 104.91) for A/(H1N1)pdm, 120.45 (95% CI 82.17, 176.57) vs. 97.86 (95% CI 81.34, 117.44) for A/H3N2 and 143.32 (95% CI 103.46, 198.53) vs. 145.54 (95% CI 122.35, 174.24) for influenza B, respectively. After adjusting for confounding factors, time since transplantation was not associated with response to vaccination. No cases of rejection or severe adverse events were detected in patients vaccinated within the first 6 months after transplantation. In conclusion, influenza vaccination within the first 6 months after transplantation is as safe and immunogenic as vaccination thereafter. Thus, administration of the influenza vaccine can be recommended as soon as 1 month after transplantation.
Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino
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.
Zuckerman, Arie J
Although concerns about vaccine safety have increased, true adverse reactions associated with hepatitis B vaccines are few, apart from minor symptoms at the site of injection and occasionally systemic reactions. There is no evidence of an association with hepatitis B vaccination and Sudden Infant Death Syndrome, Multiple Sclerosis and the Chronic Fatigue Syndrome. Hepatitis B vaccines are safe and essential for the prevention of this important and common infection.
Cheng, Allen C; Dwyer, Dominic E; Holmes, Mark; Irving, Lois B; Brown, Simon Ga; Waterer, Grant W; Korman, Tony M; Hunter, Cameron; Hewagama, Saliya; Friedman, Nadia D; Wark, Peter A; Simpson, Graham; Upham, John W; Bowler, Simon D; Senenayake, Sanjaya N; Kotsimbos, Tom C; Kelly, Paul M
The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season.
Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants
Li, Yanping; Li, Rong Cheng; Ye, Qiang; Li, Changgui; Liu, You Ping; Ma, Xiao; Li, Yanan; Zhao, Hong; Chen, Xiaoling; Assudani, Deepak; Karkada, Naveen; Han, Htay Htay; Van Der Meeren, Olivier; Mesaros, Narcisa
ABSTRACT We conducted 3 phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 months of age (Group B). In the Primary study (NCT01086423), 984 healthy infants (randomized 1:1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 (Group B) months of age, or concomitant DTPa/Hib and poliomyelitis (IPV) vaccination at 2–3–4 months of age (Control group); 825 infants received a booster dose of DTPa/Hib and IPV at 18–24 months of age (Booster study; NCT01449812). In the Pilot study, unsolicited symptoms were more frequent in Group A (16 versus 1 infant; mostly upper respiratory tract infection and pyrexia); this observation was attributed to an epidemic outbreak of viral infections. Non-inferiority of 3-dose primary vaccination with DTPa-IPV/Hib over separately administered DTPa/Hib and IPV was demonstrated for Group A (primary objective). Similar antibody concentrations were observed in all groups, except for anti-polyribosyl-ribitol phosphate and anti-poliovirus types 1–3 which were higher in DTPa-IPV/Hib recipients. Protective antibody levels against all vaccine antigens remained high until booster vaccination. Three-dose vaccination with DTPa-IPV/Hib had a clinically acceptable safety profile. PMID:27768515
Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants.
Li, Yanping; Li, Rong Cheng; Ye, Qiang; Li, Changgui; Liu, You Ping; Ma, Xiao; Li, Yanan; Zhao, Hong; Chen, Xiaoling; Assudani, Deepak; Karkada, Naveen; Han, Htay Htay; Van Der Meeren, Olivier; Mesaros, Narcisa
We conducted 3 phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received 3 doses of DTPa-IPV/Hib at 2-3-4 (Group A) or 3-4-5 months of age (Group B). In the Primary study (NCT01086423), 984 healthy infants (randomized 1:1:1) received 3 doses of DTPa-IPV/Hib at 2-3-4 (Group A) or 3-4-5 (Group B) months of age, or concomitant DTPa/Hib and poliomyelitis (IPV) vaccination at 2-3-4 months of age (Control group); 825 infants received a booster dose of DTPa/Hib and IPV at 18-24 months of age (Booster study; NCT01449812). In the Pilot study, unsolicited symptoms were more frequent in Group A (16 versus 1 infant; mostly upper respiratory tract infection and pyrexia); this observation was attributed to an epidemic outbreak of viral infections. Non-inferiority of 3-dose primary vaccination with DTPa-IPV/Hib over separately administered DTPa/Hib and IPV was demonstrated for Group A (primary objective). Similar antibody concentrations were observed in all groups, except for anti-polyribosyl-ribitol phosphate and anti-poliovirus types 1-3 which were higher in DTPa-IPV/Hib recipients. Protective antibody levels against all vaccine antigens remained high until booster vaccination. Three-dose vaccination with DTPa-IPV/Hib had a clinically acceptable safety profile.
Ropero-Álvarez, Alba María; Kurtis, Hannah J; Danovaro-Holliday, M Carolina; Ruiz-Matus, Cuauhtémoc; Andrus, Jon K
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
Herbinger, Karl-Heinz; von Sonnenburg, Frank; Nothdurft, Hans Dieter; Perona, Pamela; Borkowski, Astrid; Fragapane, Elena; Nicolay, Uwe; Clemens, Ralf
An investigational tetravalent vaccine combining pre-pandemic, MF59®-adjuvanted A/H5N1 vaccine with non-adjuvanted, trivalent, seasonal influenza vaccine has been developed, which has the potential to be used for pre-pandemic priming and to improve levels of compliance and coverage. It is important to determine whether the safety and immunogenicity of the combination vaccine is equivalent to that of the two separate vaccines when administered concomitantly. Healthy adults (n = 601) were randomly assigned to three vaccination groups to receive either: (1) tetravalent vaccine and placebo concomitantly (in separate arms) on Day 1, followed by A/H5N1 vaccine on Day 22; (2) A/H5N1 vaccine and placebo concomitantly on Day 1, followed by tetravalent vaccine on Day 22; or (3) A/H5N1 and seasonal vaccines concomitantly on Day 1, followed by A/H5N1 vaccine on Day 22. Antibody responses were measured using single radial hemolysis (SRH), haemagglutination inhibition (HI), and microneutralization (MN) assays on Days 1, 22, and 43. Solicited adverse reactions were recorded for seven days after vaccination. Spontaneous adverse events were recorded throughout the study. The tetravalent vaccine elicited antibody titers equivalent to those for separate A/H5N1 and seasonal vaccines, and sufficient to meet the European licensure criteria against A/H5N1 and all three seasonal strains. Local and systemic reactions were mainly mild to moderate. No vaccine-related serious adverse events occurred. These findings demonstrate that MF59-adjuvanted A/H5N1 and seasonal influenza vaccines had an acceptable safety profile and could be effectively administered as a tetravalent formulation, supporting the possibility of integrating pre-pandemic priming into seasonal influenza vaccination programs. PMID:24047817
Bazhan, Sergei I.
By means of a designed epidemic model, we evaluated the influence of seasonal vaccination coverage as well as a potential universal vaccine with differing efficacy on the aftermath of seasonal and pandemic influenza. The results of the modeling enabled us to conclude that, to control a seasonal influenza epidemic with a reproduction coefficient R0 ≤ 1.5, a 35% vaccination coverage with the current seasonal influenza vaccine formulation is sufficient, provided that other epidemiology measures are regularly implemented. Increasing R0 level of pandemic strains will obviously require stronger intervention. In addition, seasonal influenza vaccines fail to confer protection against antigenically distinct pandemic influenza strains. Therefore, the necessity of a universal influenza vaccine is clear. The model predicts that a potential universal vaccine will be able to provide sufficient reliable (90%) protection against pandemic influenza only if its efficacy is comparable with the effectiveness of modern vaccines against seasonal influenza strains (70%–80%); given that at least 40% of the population has been vaccinated in advance, ill individuals have been isolated (observed), and a quarantine has been introduced. If other antiepidemic measures are absent, a vaccination coverage of at least 80% is required. PMID:27668256
VACCINE INFORMATION STATEMENT Hib Vaccine ( Haemophilus Influenzae Type b) What You Need to Know Many Vaccine Information ... vis 1 Why get vaccinated? Haemophilus influenzae type b (Hib) disease is a serious disease caused by ...
Beginning in Southeast Asia, in 2003, a multi-national epizootic outbreak of H5N1 highly pathogenic avian influenza (HPAI) was identified in commercial poultry and wild bird species. This lineage, originally identified in Southern China in 1996 and then Hong Kong in 1997, caused severe morbidity an...
Jimenez-Jorge, S; de Mateo, S; Delgado-Sanz, C; Pozo, F; Casas, I; Garcia-Cenoz, M; Castilla, J; Rodriguez, C; Vega, T; Quinones, C; Martinez, E; Vanrell, J M; Gimenez, J; Castrillejo, D; Altzibar, J M; Carril, F; Ramos, J M; Serrano, M C; Martinez, A; Torner, N; Perez, E; Gallardo, V; Larrauri, A
We aimed to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in Spain using surveillance data and to compare the results with data obtained by the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine Effectiveness (I-MOVE) network. We used the test-negative case–control design, with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from the cycEVA study. Cases were laboratory-confirmed influenza patients with the predominant influenza virus of each season, and controls were those testing negative for any influenza virus. We calculated the overall and age-specific adjusted VE. Although the number of patients recorded in the SISS was three times higher than that in the cycEVA study, the quality of information for important variables, i.e. vaccination status and laboratory results, was high in both studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar during the study period. For elderly patients (> 59 years), the SISS estimates were slightly lower than those of cycEVA, and estimates for children (0–14 years) were higher using SISS in two of the three seasons studied. Enhancing the SISS by collecting the date of influenza vaccination and reducing the percentage of patients with incomplete information would optimise the system to provide reliable annual influenza VE estimates to guide influenza vaccination policies.
Sasaki, Eita; Kuramitsu, Madoka; Momose, Haruka; Kobiyama, Kouji; Aoshi, Taiki; Yamada, Hiroshi; Ishii, Ken J; Mizukami, Takuo; Hamaguchi, Isao
Vaccines are administered to healthy humans, including infants, so the safety and efficacy must be very high. Therefore, evaluating vaccine safety in preclinical and clinical studies, according to World Health Organization guidelines, is crucial for vaccine development and clinical use. A change in the route of administration is considered to alter a vaccine's immunogenicity. Several adjuvants have also been developed and approved for use in vaccines. However, the addition of adjuvants to vaccines may cause unwanted immune responses, including facial nerve paralysis and narcolepsy. Therefore, a more accurate and comprehensive strategy must be used to develope next-generation vaccines for ensuring vaccine safety. Previously, we have developed a system with which to evaluate vaccine safety in rats using a systematic vaccinological approach and 20 marker genes. In this study, we developed a safety evaluation system for nasally administered influenza vaccines and adjuvanted influenza vaccines using these marker genes. Expression of these genes increased dose-dependent manner when mice were intranasally administered the toxicity reference vaccine. When the adjuvant CpG K3 or a CpG-K3-combined influenza vaccine was administered intranasally, marker gene expression increased in a CpG-K3-dose-dependent way. A histopathological analysis indicated that marker gene expression correlated with vaccine- or adjuvant-induced phenotypic changes in the lung and nasal mucosa. We believe that the marker genes expression analyses will be useful in preclinical testing, adjuvant development, and selecting the appropriate dose of adjuvant in nasal administration vaccines.
Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo Giuseppe; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele
Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P<0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P<0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future.
Brandt, C; Rabenau, H F; Bornmann, S; Gottschalk, R; Wicker, S
The emergence of the influenza A(H1N1)2009 virus provided a major challenge to health services around the world. However, vaccination rates for the public and for healthcare workers (HCWs) have remained low. We performed a study to review the reasons put forward by HCWs to refuse immunisation with the pandemic vaccine in 2009/10 and characterise attitudes in the influenza season 2010/11 due to the emergence of influenza A(H1N1)2009. A survey among HCWs and medical students in the clinical phase of their studies was conducted, using an anonymous questionnaire, at a German university hospital during an influenza vaccination campaign. 1,366 of 3,900 HCWs (35.0%) were vaccinated in the 2010/11 influenza season. Of the vaccinated HCWs, 1,323 (96.9%) completed the questionnaire in addition to 322 vaccinated medical students. Of the 1,645 vaccinees who completed the questionnaire, 712 had not been vaccinated against the influenza A(H1N1)2009 virus in the 2009/10 season. The main reason put forward was the objection to the AS03 adjuvants (239/712, 33.6%). Of the HCWs and students surveyed, 270 of 1,645 (16.4%) stated that the pandemic had influenced their attitude towards vaccination in general. Many German HCWs remained unconvinced of the safety of the pandemic (adjuvanted) influenza vaccine. For this reason, effective risk communication should focus on educating the public and HCWs about influenza vaccine safety and the benefits of vaccination.
Farrukh, Muhammad Junaid; Ming, Long Chiau; Zaidi, Syed Tabish Razi; Khan, Tahir Mehmood
Influenza vaccination is strongly recommended by World Health Organisation on a yearly basis. The rate of immunization in Pakistan is suboptimal. High cost, traditional norms, customs and low levels of education in Pakistan are preventing people from getting vaccinated. It is timely to include influenza vaccination in the expanded programme on immunization (EPI), which is a disease prevention programme aiming to eradicate preventable diseases through subsidized or free immunization. The Ministry of National Health Services, Regulation and Coordination, Government of Pakistan should launch a national influenza vaccine policy in view of this current situation and oversee its implementation. Healthcare professionals should promote influenza vaccination and focus on high risk groups such as the elderly, pregnant women and children. Convincing and educating family members regarding immunization of pregnant women and follow-up with parents regarding a second influenza shot for their children will further improve vaccination rates in Pakistan.
Hoft, Daniel F; Belshe, Robert B
Influenza remains a major problem causing significant morbidity and mortality annually and periodic pandemics with the potential for 10-100 fold increased mortality. Conventional vaccines can be highly effective if generated each year to match currently circulating viruses. Ongoing research focuses on producing cross-protective vaccines that induce T cell and/ or antibody responses specific for highly conserved viral epitopes. The Saint Louis University Center for Vaccine Development (SLUCVD) is highly engaged in multiple efforts to generate universally relevant influenza vaccines.
Kliner, Merav; Keenan, Alex; Sinclair, David; Ghebrehewet, Sam; Garner, Paul
Background The UK Department of Health recommends annual influenza vaccination for healthcare workers, but uptake remains low. For staff, there is uncertainty about the rationale for vaccination and evidence underpinning the recommendation. Objectives To clarify the rationale, and evidence base, for influenza vaccination of healthcare workers from the occupational health, employer and patient safety perspectives. Design Systematic appraisal of published systematic reviews. Results The quality of the 11 included reviews was variable; some included exactly the same trials but made conflicting recommendations. 3 reviews assessed vaccine effects in healthcare workers and found 1 trial reporting a vaccine efficacy (VE) of 88%. 6 reviews assessed vaccine effects in healthy adults, and VE was consistent with a median of 62% (95% CI 56 to 67). 2 reviews assessed effects on working days lost in healthcare workers (3 trials), and 3 reported effects in healthy adults (4 trials). The meta-analyses presented by the most recent reviews do not reach standard levels of statistical significance, but may be misleading as individual trials suggest benefit with wide variation in size of effect. The 2013 Cochrane review reported absolute effects close to 0 for laboratory-confirmed influenza, and hospitalisation for patients, but excluded data on clinically suspected influenza and all-cause mortality, which had shown potentially important effects in previous editions. A more recent systematic review reports these effects as a 42% reduction in clinically suspected influenza (95% CI 27 to 54) and a 29% reduction in all-cause mortality (95% CI 15 to 41). Conclusions The evidence for employer and patient safety benefits of influenza vaccination is not straightforward and has been interpreted differently by different systematic review authors. Future uptake of influenza vaccination among healthcare workers may benefit from a fully transparent guideline process by a panel representing all
Gasparini, Roberto; Amicizia, Daniela; Lai, Piero Luigi; Panatto, Donatella
Influenza viruses are adept in human populations. Indeed, they have the capacity to evade the immune system through mechanisms of mutations (antigenic drift) and major variations in surface protein expression (antigenic shift). When a major change occurs, the risk of a human pandemic arises. Three influenza pandemics occurred during the 20th century, the most serious being the Spanish influenza. The last pandemic of the past century occurred in 1968, and the responsible virus infected an estimated 1-3 million people throughout the world. The first pandemic of the present century occurred in 2009 and was sustained by a H1N1 strain (A/California/07/09). In 1997, a novel avian influenza virus, H5N1, first infected humans in China. Since its emergence, the H5N1 virus has spread from Asia to Europe and Africa, resulting in the infection of millions of poultry and wild birds. So far, 522 human cases and 322 deaths have been reported by the WHO. Many studies have therefore been performed to obtain efficacious and safe H5N1 vaccines. One of these is Aflunov(®). Aflunov is a prepandemic monovalent A/H5N1 influenza vaccine adjuvanted with MF59 produced by Novartis Vaccines and Diagnostics. In nonclinical studies conducted in rabbits, Aflunov proved to be well-tolerated, did not cause maternal or embryo-fetal toxicity, was not teratogenic, and had no effects on postnatal development. In clinical studies, Aflunov proved safe and well-tolerated in infants, children, adolescents, adults and the elderly. In the same subjects, the vaccine elicited robust immunogenicity against both homologous (A/Vietnam/1194/2004 clade 1) and heterologous viral strains (for instance, A/Indonesia/05/2005 or A/Turkey/15/2006) and induced immunologic memory. Thus, in 2010, the CHMP issued a positive opinion on Aflunov and in January 2011 Aflunov was given marketing authorization. This vaccine could be very useful in the event of adaptation of the H5N1 virus to humans, which could cause a new
Ping, Jihui; Lopes, Tiago J S; Neumann, Gabriele; Kawaoka, Yoshihiro
The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.
Herbinger, Karl-Heinz; von Sonnenburg, Frank; Nothdurft, Hans Dieter; Perona, Pamela; Borkowski, Astrid; Fragapane, Elena; Nicolay, Uwe; Clemens, Ralf
An investigational tetravalent vaccine combining pre-pandemic, MF59®-adjuvanted A/H5N1 vaccine with non-adjuvanted, trivalent, seasonal influenza vaccine has been developed, which has the potential to be used for pre-pandemic priming and to improve levels of compliance and coverage. It is important to determine whether the safety and immunogenicity of the combination vaccine is equivalent to that of the two separate vaccines when administered concomitantly. Healthy adults (n=601) were randomly assigned to three vaccination groups to receive either: (1) tetravalent vaccine and placebo concomitantly (in separate arms) on Day 1, followed by A/H5N1 vaccine on Day 22; (2) A/H5N1 vaccine and placebo concomitantly on Day 1, followed by tetravalent vaccine on Day 22; or (3) A/H5N1 and seasonal vaccines concomitantly on Day 1, followed by A/H5N1 vaccine on Day 22. Antibody responses were measured using single radial hemolysis (SRH), haemagglutination inhibition (HI), and microneutralization (MN) assays on Days 1, 22, and 43. Solicited adverse reactions were recorded for seven days after vaccination. Spontaneous adverse events were recorded throughout the study. The tetravalent vaccine elicited antibody titers equivalent to those for separate A/H5N1 and seasonal vaccines, and sufficient to meet the European licensure criteria against A/H5N1 and all three seasonal strains. Local and systemic reactions were mainly mild to moderate. No vaccine-related serious adverse events occurred. These findings demonstrate that MF59-adjuvanted A/H5N1 and seasonal influenza vaccines had an acceptable safety profile and could be effectively administered as a tetravalent formulation, supporting the possibility of integrating pre-pandemic priming into seasonal influenza vaccination programs.
Li, Xiaohui; Pushko, Peter; Tretyakova, Irina
Cases of H7N9 human infection were caused by a novel, avian-origin H7N9 influenza A virus that emerged in eastern China in 2013. Clusters of human disease were identified in many cities in China, with mortality rates approaching 30%. Pandemic concerns were raised, as historically, influenza pandemics were caused by introduction of novel influenza A viruses into immunologically naïve human population. Currently, there are no approved human vaccines for H7N9 viruses. Recombinant protein vaccine approaches have advantages in safety and manufacturing. In this review, we focused on evaluation of the expression of recombinant hemagglutinin (rHA) proteins as candidate vaccines for H7N9 influenza, with the emphasis on the role of oligomeric and particulate structures in immunogenicity and protection. Challenges in preparation of broadly protective influenza vaccines are discussed, and examples of broadly protective vaccines are presented including rHA stem epitope vaccines, as well as recently introduced experimental multi-HA VLP vaccines. PMID:26523241
... Proclamation 8472--National Influenza Vaccination Week, 2010 #0; #0; #0; Presidential Documents #0; #0; #0;#0...;Title 3-- #0;The President ] Proclamation 8472 of January 8, 2010 National Influenza Vaccination Week... week presents a window of opportunity for us to prevent a possible third wave of H1N1 flu in the...
Chou, Cheng-Hsiu; Liou, Wen-Ping; Hu, Kun-I; Loh, Ching-Hui; Chou, Chih-Chieh; Chen, Yeong-Hwang
The etiology of Bell's palsy is often unknown. We present herein two cases of adults who developed a Bell's palsy following the administration of an influenza vaccine. While the incidence is low, with the widespread recommendation for annual influenza vaccines, patients should be apprised of the possibility of this complication and the benefit of early treatment.
Gargano, Lisa M; Underwood, Natasha L; Sales, Jessica M; Seib, Katherine; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M
In 2011-2012, only 34% of 13-17 years olds in the United States (US) received seasonal influenza vaccine. Little is known about the link between parents' sources of health information, their vaccine-related attitudes, and vaccination of their adolescent against influenza. This study seeks to determine the relationship between number of sources of information on influenza vaccine, parental attitudes toward influenza vaccine, and influenza vaccine uptake in adolescents. We conducted a telephone and web-based survey among US parents of students enrolled in 6 middle and 5 high schools in Georgia. Bivariate and multivariable analyses were conducted to examine associations between the number of information sources about influenza vaccine and vaccine receipt and whether parent vaccine-related attitudes act as a mediator. The most commonly reported sources of information were: a physician/medical professional (95.0%), a family member or friend (80.6%), and television (77.2%). Parents who had higher attitude scores toward influenza vaccine were 5 times as likely to report their adolescent had ever received influenza vaccine compared to parents who had lower attitude scores (adjusted odds ratio (aOR) 5.1; 95% confidence intervals (CI) 3.1-8.4; P < 0.01). Parent vaccine-related attitudes were a significant mediator of the relationship between sources of information and vaccine receipt. In light of the low response rate and participation in an adolescent vaccination intervention, findings may not be generalizable to other populations. This study shows the importance of multiple sources of information in influencing parental decision-making about influenza vaccine for adolescents. Harnessing the power of mass media and family members and friends as health advocates for influenza vaccination can potentially help increase vaccination coverage of adolescents.
Avelino-Silva, Vivian Iida; Avelino-Silva, Thiago Junqueira; Miraglia, Joao Luiz; Miyaji, Karina Takesaki; Jacob-Filho, Wilson; Lopes, Marta Heloisa
OBJECTIVES: Population aging raises concerns regarding the increases in the rates of morbidity and mortality that result from influenza and its complications. Although vaccination is the most important tool for preventing influenza, vaccination program among high-risk groups has not reached its predetermined aims in several settings. This study aimed to evaluate the impacts of clinical and demographic factors on vaccine compliance among the elderly in a setting that includes a well-established annual national influenza vaccination campaign. METHODS: This cross-sectional study included 134 elderly patients who were regularly followed in an academic medical institution and who were evaluated for their influenza vaccination uptake within the last five years; in addition, the demographic and clinical characteristics and the reasons for compliance or noncompliance with the vaccination program were investigated. RESULTS: In total, 67.1% of the participants received the seasonal influenza vaccine in 2009. Within this vaccination-compliant group, the most common reason for vaccine uptake was the annual nationwide campaign (52.2%; 95% CI: 41.4–62.9%); compared to the noncompliant group, a higher percentage of compliant patients had been advised by their physician to take the vaccine (58.9% vs. 34.1%; p<0.01). CONCLUSION: The education of patients and health care professionals along with the implementation of immunization campaigns should be evaluated and considered by health authorities as essential for increasing the success rate of influenza vaccination compliance among the elderly. PMID:22189726
Yewdell, Jonathan W
Year in and year out, influenza viruses exact a deadly and expensive toll on humanity. Current vaccines simply do not keep pace with viral immune evasion, providing partial protection, at best, among various age groups. A quantum leap in understanding the basic principles of the adaptive and innate immune responses to influenza viruses offers the opportunity to develop vaccines that forestall, and potentially ultimately defeat, influenza virus antigenic variation.
Hashem, Anwar M.
Current influenza vaccines afford substantial protection in humans by inducing strain-specific neutralizing antibodies (Abs). Most of these Abs target highly variable immunodominant epitopes in the globular domain of the viral hemagglutinin (HA). Therefore, current vaccines may not be able to induce heterosubtypic immunity against the divergent influenza subtypes. The identification of broadly neutralizing Abs (BnAbs) against influenza HA using recent technological advancements in antibody libraries, hybridoma, and isolation of single Ab-secreting plasma cells has increased the interest in developing a universal influenza vaccine as it could provide life-long protection. While these BnAbs can serve as a source for passive immunotherapy, their identification represents an important step towards the design of such a universal vaccine. This review describes the recent advances and approaches used in the development of universal influenza vaccine based on highly conserved HA regions identified by BnAbs. PMID:25785268
Hashem, Anwar M
Current influenza vaccines afford substantial protection in humans by inducing strain-specific neutralizing antibodies (Abs). Most of these Abs target highly variable immunodominant epitopes in the globular domain of the viral hemagglutinin (HA). Therefore, current vaccines may not be able to induce heterosubtypic immunity against the divergent influenza subtypes. The identification of broadly neutralizing Abs (BnAbs) against influenza HA using recent technological advancements in antibody libraries, hybridoma, and isolation of single Ab-secreting plasma cells has increased the interest in developing a universal influenza vaccine as it could provide life-long protection. While these BnAbs can serve as a source for passive immunotherapy, their identification represents an important step towards the design of such a universal vaccine. This review describes the recent advances and approaches used in the development of universal influenza vaccine based on highly conserved HA regions identified by BnAbs.
Deng, Lei; Cho, Ki Joon; Fiers, Walter; Saelens, Xavier
The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.
Deng, Lei; Cho, Ki Joon; Fiers, Walter; Saelens, Xavier
The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future. PMID:26344949
A dose-ranging study of MF59®-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination
Reisinger, Keith S; Holmes, Sandra J; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria
Background During development of an A/H1N1 pandemic influenza vaccine, this study was performed to identify the antigen and adjuvant content which would provide optimal antibody response and persistence in adults and the elderly. Dose-sparing strategies, such as inclusion of adjuvants, are critical in ensuring the widest possible population coverage in the event of an influenza pandemic, despite a limited global capacity for vaccine manufacture. Methods Healthy subjects aged 18−64 years (n = 1240) and ≥65 years (n = 1352) were vaccinated with 1 of 8 investigational vaccine formulations varying in antigen quantity (3.75 µg to 30 µg of hemagglutinin) and MF59® adjuvant (none, half dose, or full dose). All subjects received 2 vaccine doses administered 3 weeks apart. Antibody response was assessed by hemagglutination inhibition assay 1 and 3 weeks after administration of first and second doses. Antibody persistence was assessed after 6 and 12 mo. Vaccine safety was monitored over 12 mo. Results All 8 investigational A/H1N1 vaccine formulations were well tolerated, and rapidly induced high antibody titers which met all of the Center for Biologics Evaluation and Research (CBER) and Committee for Medicinal Products for Human Use (CHMP) licensure criteria 3 weeks after one dose. The highest antibody titers were observed in participants vaccinated with higher quantities of antigen and adjuvant. Conclusion A single vaccine dose containing 3.75 µg of A/California/7/2009 (H1N1) antigen with MF59 adjuvant was identified as optimal for young to middle-aged (18−64 years) and older (≥65 years) adult populations. PMID:25424947
Ortiz, Justin R; Neuzil, Kathleen M; Ahonkhai, Vincent I; Gellin, Bruce G; Salisbury, David M; Read, Jennifer S; Adegbola, Richard A; Abramson, Jon S
Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life. In April 2012, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended revisions to the WHO position paper on influenza vaccines. For the first time, SAGE recommended pregnant women should be made the highest priority for inactivated seasonal influenza vaccination. However, the variable maternal influenza vaccination coverage in countries with pre-existing maternal influenza vaccine recommendations underscores the need to understand and to address the discrepancy between recommendations and implementation success. We present the outcome of a multi-stakeholder expert consultation on inactivated influenza vaccination in pregnancy. The creation and implementation of vaccine policies and regulations require substantial resources and capacity. As with all public health interventions, the existence of perceived and real risks of vaccination will necessitate effective and transparent risk communication. Potential risk allocation and sharing mechanisms should be addressed by governments, vaccine manufacturers, and other stakeholders. In resource-limited settings, vaccine-related issues concerning supply, formulation, regulation, evidence evaluation, distribution, cost-utility, and post-marketing safety surveillance need to be addressed. Lessons can be learned from the Maternal and Neonatal Tetanus Elimination Initiative as well as efforts to increase vaccine coverage among pregnant
Dicko, Alassane; Santara, Gaoussou; Mahamar, Almahamoudou; Sidibe, Youssoufa; Barry, Amadou; Dicko, Yahia; Diallo, Aminata; Dolo, Amagana; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Strezova, Ana; Borys, Dorota; Schuerman, Lode
Background: Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was previously shown to be immunogenic and well tolerated in Malian children. Data on booster vaccination with a fourth consecutive dose of PHiD-CV are available for Europe, Asia and Latin America but are lacking for Africa. The present study evaluated further the safety, reactogenicity and immunogenicity of a fourth consecutive (booster) dose of PHiD-CV. Results: Low incidences of AEs with grade 3 intensity (2.1% of subjects) were observed. There were no reports of large swelling reactions and serious adverse events. One month post-booster vaccination, for each vaccine pneumococcal serotype, at least 97.8% of subjects had antibody concentrations ≥ 0.2 μg/ml, and at least 97.1% of subjects had opsonophagocytic activity ≥ 8. From pre- to post-booster, a 12.3-fold increase in anti-protein D geometric mean concentration was observed. Methods: This phase III, open-label study was conducted in Ouelessebougou, Mali, between November 2009 and June 2010. The study population consisted of Malian children previously primed (3 doses) with PHiD-CV in study NCT00678301 receiving a fourth consecutive (booster) dose of PHiD-CV in the second year of life. The incidences of adverse events (AEs) with grade 3 intensity (primary objective) or of any intensity (secondary objective), and the immunogenicity (secondary objective) of the PHiD-CV booster dose were assessed. Conclusion: A booster dose of PHiD-CV was well tolerated when administered to Malian children in the second year of life and was highly immunogenic for all 10 vaccine pneumococcal serotypes and NTHi protein D. (ClinicalTrials.gov identifier: NCT00985465) PMID:23291945
Shin, Jeong-Hwa; Mo, Jong Seo; Kim, Jong-Nyeo; Mo, In-pil
In Korea, several outbreaks of low pathogenic AI (H9N2) viral infections leading to decreased egg production and increased mortality have been reported on commercial farms since 1996, resulting in severe economic losses. To control the H9N2 LPAI endemic, the Korea Veterinary Authority has permitted the use of the inactivated H9N2 LPAI vaccine since 2007. In this study, we developed a killed vaccine using a low pathogenic H9N2 AI virus (A/chicken/Korea/ADL0401) and conducted safety and efficacy tests in commercial layer farms while focusing on analysis of factors that cause losses to farms, including egg production rate, egg abnormality, and feed efficiency. The egg production rate of the control group declined dramatically 5 days after the challenge. There were no changes in feed consumption of all three groups before the challenge, but rates of the control declined afterward. Clinical signs in the vaccinated groups were similar, and a slight decline in feed consumption was observed after challenge; however, this returned to normal more rapidly than the control group and commercial layers. Overall, the results of this study indicate that the safety and efficacy of the vaccine are adequate to provide protection against the AI field infection (H9N2) epidemic in Korea. PMID:27051337
Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence
Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine.
Spinner, Justin L.; Oberoi, Hardeep S.; Yorgensen, Yvonne M.; Poirier, Danielle S.; Burkhart, David J.; Plante, Martin; Evans, Jay T.
Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response. PMID:26392012
Spinner, Justin L; Oberoi, Hardeep S; Yorgensen, Yvonne M; Poirier, Danielle S; Burkhart, David J; Plante, Martin; Evans, Jay T
Influenza is a vaccine-preventable contagious respiratory illness caused by influenza (flu) viruses which can lead to hospitalization and sometimes even death. Current flu vaccines delivered intramuscularly (IM) or intradermally (ID) are less effective at eliciting protective mucosal immune responses and vaccines delivered intranasally (IN) possess potential safety concerns. Sublingual (SL) vaccination is a promising alternative route for vaccine delivery which has been indicated as safe and effective at inducing protective immune responses in both systemic and mucosal compartments. We evaluated the efficacy of methylglycol chitosan (MGC) and a synthetic toll-like receptor 4 agonist (CRX-601), alone or in combination, for improving systemic and mucosal immune responses to a monovalent detergent-split flu virus vaccine delivered SL. SL vaccination of mice with split-flu vaccine formulated with either MGC or CRX-601 resulted in specific serum IgG and mucosal IgA titers that were significantly greater than titers from non-adjuvanted vaccination and equivalent to or greater than titers in mice vaccinated IM. Our results demonstrate that SL vaccination utilizing MGC or CRX-601 as adjuvants is a viable alternative route of vaccination for flu which can elicit systemic immune responses equivalent to or greater than IM vaccination with the added benefit of stimulating a robust specific mucosal immune response.
Samelson, Renee; Siddiqui, Maryam M.; Paglia, Michael J.; Strassberg, Emmie R.; Kelly, Elizabeth; Murtough, Katie L.; Schulkin, Jay
ACOG's research department recruited four medical centers to participate in a study on the attitudes and practices of medical providers and pregnant patients regarding influenza vaccination. Medical providers and patients were given voluntary surveys and medical record data was collected over two flu seasons, from 2013 to 2015. Discrepancies between self-reports of medical providers and patients and medical records were observed. Nearly 80% of patients self-reported accepting the influenza vaccine, but medical record data only reported 36% of patients accepting the vaccine. Similarly, all medical providers reported giving recommendations for the vaccine, but only 85% of patients reported receiving a recommendation. Age, education, a medical provider's recommendation, and educational materials were found to positively influence patient beliefs about the influenza vaccine. Accepting the vaccine was influenced by a patient's previous actions, beliefs, and a medical provider's recommendation. Patients who reported previously not accepting the vaccine and had negative feelings towards the vaccine but accepted it while pregnant reported concern for the health and safety of their baby. Future research should focus on groups that may be less likely to accept the vaccine and ways to dispel negative myths. Medical provider should continue to strongly recommend the vaccine and provide educational materials. PMID:27559272
Cheng, Allen C; Kotsimbos, Tom; Kelly, Paul M
We provide estimates of the influenza vaccine protection against hospitalisation with laboratory-confirmed influenza in the 2014 Australian season where the A/H1N1/pdm09 strain predominated. This was performed using a case-test negative study design as part of a national sentinel surveillance system in Australia. Vaccine effectiveness was estimated as (1-OR)×100% where the odds ratio of vaccination in cases vs test negative participants was estimated from a conditional logistic regression. Between April and November, 1692 adult patients were admitted with laboratory-confirmed influenza. Vaccine effectiveness was estimated from 1283 patients with influenza and 1116 test negative patients where vaccination status was ascertained. Vaccination was associated with a reduction in the risk of hospitalisation with influenza of 51.5% (95% CI: 41.6%, 59.7%) in all patients, and a reduction of 50.7% (95% CI: 40.1%, 59.3%) in the target population for vaccination. We estimate that the influenza vaccine was moderately protective against hospitalisation with laboratory-confirmed influenza during the 2014 influenza season in Australia.
Banzhoff, Angelika; Stoddard, Jeffrey J
Seasonal influenza causes clinical illness and hospitalization in all age groups; however, conventional inactivated vaccines have only limited efficacy in young children. MF59(®), an oil-in-water emulsion adjuvant, has been used since the 1990s to enhance the immunogenicity of influenza vaccines in the elderly, a population with waning immune function due to immunosenescence. Clinical trials now provide information to support a favorable immunogenicity and safety profile of MF59-adjuvanted influenza vaccine in young children. Published data indicate that Fluad(®), a trivalent seasonal influenza vaccine with MF59, was immunogenic and well tolerated in young children, with a benefit/risk ratio that supports routine clinical use. A recent clinical trial also shows that Fluad provides high efficacy against PCR-confirmed influenza. Based on the results of clinical studies in children, the use of MF59-adjuvanted vaccine offers the potential to enhance efficacy and make vaccination a viable prevention and control strategy in this population.
Murcia, Pablo R; Baillie, Gregory J; Stack, J Conrad; Jervis, Carley; Elton, Debra; Mumford, Jennifer A; Daly, Janet; Kellam, Paul; Grenfell, Bryan T; Holmes, Edward C; Wood, James L N
Influenza A viruses are characterized by their ability to evade host immunity, even in vaccinated individuals. To determine how prior immunity shapes viral diversity in vivo, we studied the intra- and interhost evolution of equine influenza virus in vaccinated horses. Although the level and structure of genetic diversity were similar to those in naïve horses, intrahost bottlenecks may be more stringent in vaccinated animals, and mutations shared among horses often fall close to putative antigenic sites.
McLennan, Stuart; Wicker, Sabine
Despite all that is known about the dangers of nosocomial transmission of influenza to the vulnerable patient populations in our healthcare facilities, and the benefits of the influenza vaccination, the low rates of influenza vaccination among healthcare workers (HCWs) internationally shows no sign of significant improvement. With the current voluntary 'opt-in' programmes clearly failing to adequately address this issue, the time has undoubtedly come for a new approach to vaccination to be implemented. Two different approaches to vaccination delivery have been suggested to rectify this situation, mandatory vaccination and 'opt-out' declination forms. It is suggested, however, that these two approaches are inadequate when used by themselves. In order to protect the most vulnerable patients in our healthcare facilities as best we can from serious harm or death caused by nosocomial transmission of influenza, while at the same time respecting HCWs autonomy, and in many jurisdictions, the related legal right to refuse medical treatment, it is recommended that 'op-out' declination forms should be used in conjunction with restricted mandatory vaccination. This 'combined' approach would allow any HCW to refuse the influenza vaccination, but would make the influenza vaccination a mandatory requirement for working in areas where the most vulnerable patients are cared for. Those HCWs not willing to be vaccinated should be required to work in other areas of healthcare.
Jagadesh, Anitha; Salam, Abdul Ajees Abdul; Mudgal, Piya Paul; Arunkumar, Govindakarnavar
Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. However, antigenic shifts and drifts are major concerns with influenza virus, requiring effective global monitoring and updating of vaccines. Current vaccines are standardized primarily based on the amount of hemagglutinin, a major surface antigen, which chiefly constitutes these preparations along with the varying amounts of neuraminidase (NA). Anti-influenza drugs targeting the active site of NA have been in use for more than a decade now. However, NA has not been approved as an effective antigenic component of the influenza vaccine because of standardization issues. Although some studies have suggested that NA antibodies are able to reduce the severity of the disease and induce a long-term and cross-protective immunity, a few major scientific issues need to be addressed prior to launching NA-based vaccines. Interestingly, an increasing number of studies have shown NA to be a promising target for future influenza vaccines. This review is an attempt to consolidate studies that reflect the strength of NA as a suitable vaccine target. The studies discussed in this article highlight NA as a potential influenza vaccine candidate and support taking the process of developing NA vaccines to the next stage.
The Vaccine Safety Datalink (VSD) is a collaborative project between the National Immunization Program of the Centers for Disease Control and Prevention (CDC) and several large health maintenance organizations (HMOs) in the United States. The project began in 1990 with the primary purpose of rigorously evaluating concerns about the safety of vaccines. Computerized data on vaccination, medical outcome (e.g. hospital discharge, outpatient visits, emergency room visits, and deaths), and covariate data (e.g. birth certificates and census) are prospectively collected at multiple HMOs (initially four) and linked under joint protocol for analyses. Approximately 6 million people (2% of the US population) are members of HMOs participating in the VSD. The VSD has proven to be a valuable resource that has provided important information on a number of vaccine safety issues. The databases and infrastructure created for the VSD have also provided opportunities to address other immunization questions including vaccination coverage and cost-effectiveness. In a recent investigation of intussusception following rotavirus vaccination, the VSD methodology was expanded to include 10 managed care organizations. A cohort study was conducted that allowed estimation of incidence rates of intussusception and attributable risks associated with rotavirus vaccine.
Bettinger, J A; Rouleau, I; Gariepy, M C; Bowie, W R; Valiquette, L; Vanderkooi, O G; Kellner, J D; Coleman, B L; McNeil, S A; McCarthy, A; De Serres, G
In 2011 and 2012, a nationwide Canadian vaccine safety surveillance network rapidly collected safety data from healthcare workers (HCW) during the first weeks of the annual influenza vaccination campaign. This network provided the first available post-marketing safety data on seasonal influenza vaccines with information on background rates as a comparator. In 2012, these data were used to investigate a possible safety concern regarding a particular vaccine. An online questionnaire was provided to participating HCW two weeks before the annual influenza vaccination campaign for controls, and eight days after influenza vaccination for vaccinees. Control and vaccinees were requested to report health events occurring in the seven days prior to receiving the questionnaire. Control data were used to calculate background rates. HCW reporting a severe event were followed-up by telephone within 48 hours of the online report to validate the report and check on their health status. More than 22,000 vaccinated HCW were enrolled and surveyed over two seasons and > 90% reported no severe event following vaccination. Validated severe event rates were similar in vaccinated HCW and unvaccinated HCW (2.2% vs 2.3%; p < 0.70). The questionnaire was accurately completed for most reported symptoms, matched the validated report and was able to detect events of interest. Prior to the safety concern, the implicated vaccine was in use at one centre. Reassuring safety data were provided to public health authorities 48 hours after the vaccine was temporarily suspended. Data from this and similar networks can be used for rapid evaluation of vaccine safety and for safety assessment as required by the European Medicines Agency in 2015.
Rodgers, Loren; Pabst, Laura J; Zhu, Liping; Chaves, Sandra S
Annual influenza vaccination is recommended for everyone ≥ 6 months in the U.S. During the 2013-14 influenza season, in addition to trivalent influenza vaccines, quadrivalent vaccines were available, protecting against two influenza A and two influenza B viruses. We analyzed 1,976,443 immunization records from six sentinel sites to compare influenza vaccine usage among children age 6 months-18 years. A total of 983,401 (49.8%) influenza vaccine doses administered were trivalent and 920,333 (46.6%) were quadrivalent (unknown type: 72,709). Quadrivalent vaccine administration varied by age and was least frequent among those <2 years of age.
Aichinger, Gerald; Grohmann-Izay, Barbara; van der Velden, Maikel V W; Fritsch, Sandor; Koska, Manuela; Portsmouth, Daniel; Hart, Mary Kate; El-Amin, Wael; Kistner, Otfried; Barrett, P Noel
Studies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 μg of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, a post hoc age-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-μg- and 7.5-μg-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01320696.).
Murphy, Timothy F
Infections due to nontypeable Haemophilus influenzae result in enormous global morbidity in two clinical settings: otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Recurrent otitis media affects up to 20% of children and results in hearing loss, delays in speech and language development and, in developing countries, chronic suppurative otitis media. Infections in people with COPD result in clinic and emergency room visits, hospital admissions, and respiratory failure. An effective vaccine would prevent morbidity, help control health care costs, and reduce antibiotic use, a major contributor to the global crisis in bacterial antibiotic resistance. The widespread use of the pneumococcal conjugate vaccines is causing a relative increase in H. influenzae otitis media. The partial protection against H. influenzae otitis media induced by the pneumococcal H. influenzae protein D conjugate vaccine represents a proof of principle of the feasibility of a vaccine for nontypeable H. influenzae. An ideal vaccine antigen should be conserved among strains, have abundant epitopes on the bacterial surface, be immunogenic, and induce protective immune responses. Several surface proteins of H. influenzae have been identified as potential vaccine candidates and are in various stages of development. With continued research, progress toward a broadly effective vaccine to prevent infections caused by nontypeable H. influenzae is expected over the next several years.
Blank, Patricia R; Szucs, Thomas D
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.
Kreijtz, Joost H C M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F
Influenza viruses of the H5N1 subtype cause an ever-increasing number of bird-to-human transmissions and a pandemic outbreak caused by these viruses is imminent. Therefore, the availability of safe and effective vaccines is highly desirable and their development considered a priority. However, using production and use of seasonal influenza vaccine as template for the production of pandemic H5N1 vaccines did not yield effective vaccines. High antigen doses were required to induce appreciable antibody responses. In addition, limited production capacity and long production times are other disadvantages of conventional influenza vaccine preparations. Here, we review recent developments that will contribute to a more rapid availability of sufficient doses of highly efficacious and safe pandemic influenza vaccines. The new developments include the establishment of novel methods to prepare vaccine strains, novel production technologies and the use of novel adjuvants and alternative vaccine formulations.
Kim, Han-Joon; Jeon, Sang-Won; Yoon, Ho-Kyoung
Human influenza is a contagious respiratory illness caused by the influenza virus. The influenza vaccination is recommended annually, but several adverse effects related to allergic reactions have been reported. Panic attacks are also known to occur, but no case of a panic attack adverse effect has been reported in South Korea. We present two cases of panic disorder patients whose symptoms were aggravated by the influenza vaccination. We assumed that dysregulation of T-lymphocytes in panic disorder patients could have a role in activating various kinds of cytokines and chemokines, which then can lead to panic attack aggravation. PMID:27776395
On September 15, 2009, the Food and Drug Administration approved the manufacture of four influenza A (H1N1) 2009 monovalent vaccines. Before release of the first batches of the vaccine on September 30, intent to receive the vaccine was estimated at 50% among selected U.S. adult populations and as high as 70% for children. However, studies in previous years of seasonal influenza vaccination in children, who might require 2 doses based on age and prior vaccination status, have indicated poor compliance with recommendations. To measure intent to receive H1N1 and seasonal influenza vaccines among children and adults, during August 28-29, 2009, the North Carolina Center for Public Health Preparedness, with state and local public health officials, conducted a community assessment in two counties. This report summarizes the results of that assessment, which determined that 64% of adults reported intent to receive H1N1 vaccine. In addition, 65% of parents reported intent to have all their children (aged 6 months to <18 years) vaccinated with H1N1 vaccine, and 51% said they would have all their children vaccinated with both H1N1 and seasonal influenza vaccines. The most commonly reported reasons for not intending to receive H1N1 vaccine were belief in a low likelihood of infection (18%) and concern over vaccine side effects (14%); 85% of participants said they received their H1N1 information from television. To increase coverage with H1N1 and seasonal influenza vaccines, public health departments should use television to focus public health messages on the risks for infection and severe illness and the safety profile of the vaccine.
Porter, Chad K; Fitamaurice, Gina; Tribble, David R; Armstrong, Adam W; Mostafa, Manal; Riddle, Mark S
Though no avian influenza vaccine currently exists, development efforts have increased. Given recent reports of suboptimal vaccination rates among US military personnel, we sought to assess factors associated with a willingness to receive a hypothetical avian influenza vaccine. A self-administered questionnaire was completed by US military personnel during mid-deployment to Iraq, Afghanistan, and surrounding regions. Respondents were predominately male (86.2%), Army (72.1%), and enlisted (86.3%) with a mean age of 29.6 y. The majority (77.1%) agreed to receive an avian influenza vaccine if available. Exploratory factor analysis (EFA) identified two factors, vaccine importance and disease risk, that best described the individual perceptions and both were associated with an increased willingness to receive the hypothetical vaccine (OR: 8.2 and 1.6, respectively). Importantly, after controlling for these factors differences in the willingness to receive this hypothetical vaccine were observed across gender and branch of service. These results indicated that targeted education on vaccine safety and efficacy as well as disease risk may modify vaccination patterns in this population.
... Vaccines--Amendment Authority: 42 U.S.C. 247d-6d. ACTION: Notice of amendment to the September 28, 2009... and Emergency Preparedness Act for H5N1, H2, H6, H7, H9 and 2009-H1N1 Vaccines: Whereas there are or... September 28, 2009 declaration extended through February 28, 2010 for vaccines against influenza...
Mossad, Sherif B
Last year, the influenza vaccine did not match the circulating strains very well, and its overall protective efficacy was only 40%. All three antigens contained in the 2008-2009 vaccine are new. Surveillance data from the Southern Hemisphere during the summer of 2008 show that this vaccine is expected to match well the circulating strains in the Northern Hemisphere.
Chaussee, Michael S; Sandbulte, Heather R; Schuneman, Margaret J; Depaula, Frank P; Addengast, Leslie A; Schlenker, Evelyn H; Huber, Victor C
Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with Streptococcus pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-γ which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete.
Immunogenicity and safety of a pentavalent acellular pertussis combined vaccine including diphtheria, tetanus, inactivated poliovirus and conjugated Haemophilus Influenzae type b polysaccharide for primary vaccination at 2, 3, 4 or 3, 4, 5 months of age in infants in China.
Li, Rong Cheng; Li, Feng Xiang; Li, Yan Ping; Hou, Qi Ming; Li, Chang Gui; Li, Ya Nan; Chen, Fu Sheng; Hu, Xue Zhong; Su, Wen Bin; Zhang, Shu Min; Fang, Han Hua; Ye, Qiang; Zeng, Tian De; Liu, Tao Xuan; Li, Xiu Bi; Huang, Yun Neng; Deng, Man Ling; Zhang, Yan Ping; Ortiz, Esteban
The aim was to demonstrate the immunogenicity and safety of a DTaP-IPV//PRP-T combined vaccine (Pentaxim(®)) compared to individual vaccines in infants in the People's Republic of China. Infants (N=792) were randomly assigned to receive DTaP-IPV//PRP-T at 2, 3 and 4 months of age (Group A) or 3, 4 and 5 months of age (Group B), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib(®)) and IPV (Imovax(®) Polio) at 3, 4 and 5 months of age (Group C). Antibody titers were measured pre- and 1 month after the third vaccination; non-inferiority analyses were performed for seroprotection/seroconversion (SP/SC) rates. Safety was assessed 1 month after the primary series. SP/SC rates for the DTaP-IPV//PRP-T vaccine were high and non-inferior to the controls. Reactogenicity was low for each group and no hypotonic hyporesponsive episode or seizure was reported. In conclusion, the DTaP-IPV//PRP-T vaccine was highly immunogenic, non-inferior to the commercially available control vaccines and had a good safety profile for both primary administration schedules.
Equine influenza (EI) is a major respiratory disease of horses, which is still causing substantial outbreaks worldwide despite several decades of surveillance and prevention. Alongside quarantine procedures, vaccination is widely used to prevent or limit spread of the disease. The panel of EI vaccines commercially available is probably one of the most varied, including whole inactivated virus vaccines, Immuno-Stimulating Complex adjuvanted vaccines (ISCOM and ISCOM-Matrix), a live attenuated equine influenza virus (EIV) vaccine and a recombinant poxvirus-vectored vaccine. Several other strategies of vaccination are also evaluated. This systematic review reports the advances of EI vaccines during the last few years as well as some of the mechanisms behind the inefficient or sub-optimal response of horses to vaccination. PMID:26344892
Sullivan, K M; Monto, A S; Foster, D A
Four inactivated influenza vaccines (containing the recommended antigens for the 1985-1986 influenza season) of various antigenic concentration levels were randomly administered to 140 study participants. The effect of the increasing antigen concentration resulted in significantly higher influenza hemagglutination inhibition (HI) antibody levels 3 weeks after vaccination for the A/H1N1 antigen but not for the A/H3N2 or B antigens. Also, at 3 weeks after vaccination, there were significantly lower antibody titer levels associated with increasing age for the A/H1N1 and B antigens (adjusting for the prevaccination antibody titer and antigen content).
Lei, Yang; Pereira, Jennifer A.; Quach, Susan; Bettinger, Julie A.; Kwong, Jeffrey C.; Corace, Kimberly; Garber, Gary; Feinberg, Yael; Guay, Maryse
Background The aim of this study was to understand online public perceptions of the debate surrounding the choice of annual influenza vaccinations or wearing masks as a condition of employment for healthcare workers, such as the one enacted in British Columbia in August 2012. Methods Four national and 82 local (British Columbia) Canadian online news sites were searched for articles posted between August 2012 and May 2013 containing the words “healthcare workers” and “mandatory influenza vaccinations/immunizations” or “mandatory flu shots and healthcare workers.” We included articles from sources that predominantly concerned our topic of interest and that generated reader comments. Two researchers coded the unedited comments using thematic analysis, categorizing codes to allow themes to emerge. In addition to themes, the comments were categorized by: 1) sentiment towards influenza vaccines; 2) support for mandatory vaccination policies; 3) citing of reference materials or statistics; 4) self-identified health-care worker status; and 5) sharing of a personal story. Results 1163 comments made by 648 commenters responding to 36 articles were analyzed. Popular themes included concerns about freedom of choice, vaccine effectiveness, patient safety, and distrust in government, public health, and the pharmaceutical industry. Almost half (48%) of commenters expressed a negative sentiment toward the influenza vaccine, 28% were positive, 20% were neutral, and 4% expressed mixed sentiment. Of those who commented on the policy, 75% did not support the condition to work policy, while 25% were in favour. Of the commenters, 11% self-identified as healthcare workers, 13% shared personal stories, and 18% cited a reference or statistic. Interpretation The perception of the influenza vaccine in the comment sections of online news sites is fairly poor. Public health agencies should consider including online forums, comment sections, and social media sites as part of their
Flannery, Brendan; Thompson, Mark G.; Gaglani, Manjusha; Jackson, Michael L.; Monto, Arnold S.; Nowalk, Mary Patricia; Talbot, H. Keipp; Treanor, John J.; Belongia, Edward A.; Murthy, Kempapura; Jackson, Lisa A.; Petrie, Joshua G.; Zimmerman, Richard K.; Griffin, Marie R.; McLean, Huong Q.; Fry, Alicia M.
BACKGROUND: Few observational studies have evaluated the relative effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines against medically attended laboratory-confirmed influenza. METHODS: We analyzed US Influenza Vaccine Effectiveness Network data from participants aged 2 to 17 years during 4 seasons (2010–2011 through 2013–2014) to compare relative effectiveness of LAIV and IIV against influenza-associated illness. Vaccine receipt was confirmed via provider/electronic medical records or immunization registry. We calculated the ratio (odds) of influenza-positive to influenza-negative participants among those age-appropriately vaccinated with either LAIV or IIV for the corresponding season. We examined relative effectiveness of LAIV and IIV by using adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression. RESULTS: Of 6819 participants aged 2 to 17 years, 2703 were age-appropriately vaccinated with LAIV (n = 637) or IIV (n = 2066). Odds of influenza were similar for LAIV and IIV recipients during 3 seasons (2010–2011 through 2012–2013). In 2013–2014, odds of influenza were significantly higher among LAIV recipients compared with IIV recipients 2 to 8 years old (OR 5.36; 95% CI, 2.37 to 12.13). Participants vaccinated with LAIV or IIV had similar odds of illness associated with influenza A/H3N2 or B. LAIV recipients had greater odds of illness due to influenza A/H1N1pdm09 in 2010–2011 and 2013–2014. CONCLUSIONS: We observed lower effectiveness of LAIV compared with IIV against influenza A/H1N1pdm09 but not A(H3N2) or B among children and adolescents, suggesting poor performance related to the LAIV A/H1N1pdm09 viral construct. PMID:26738884
Yamin, Dan; Gavious, Arieh; Solnik, Eyal; Davidovitch, Nadav; Balicer, Ran D; Galvani, Alison P; Pliskin, Joseph S
Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks.
Yamin, Dan; Gavious, Arieh; Solnik, Eyal; Davidovitch, Nadav; Balicer, Ran D.; Galvani, Alison P.; Pliskin, Joseph S.
Influenza vaccination is the primary approach to prevent influenza annually. WHO/CDC recommendations prioritize vaccinations mainly on the basis of age and co-morbidities, but have never considered influenza infection history of individuals for vaccination targeting. We evaluated such influenza vaccination policies through small-world contact networks simulations. Further, to verify our findings we analyzed, independently, large-scale empirical data of influenza diagnosis from the two largest Health Maintenance Organizations in Israel, together covering more than 74% of the Israeli population. These longitudinal individual-level data include about nine million cases of influenza diagnosed over a decade. Through contact network epidemiology simulations, we found that individuals previously infected with influenza have a disproportionate probability of being highly connected within networks and transmitting to others. Therefore, we showed that prioritizing those previously infected for vaccination would be more effective than a random vaccination policy in reducing infection. The effectiveness of such a policy is robust over a range of epidemiological assumptions, including cross-reactivity between influenza strains conferring partial protection as high as 55%. Empirically, our analysis of the medical records confirms that in every age group, case definition for influenza, clinical diagnosis, and year tested, patients infected in the year prior had a substantially higher risk of becoming infected in the subsequent year. Accordingly, considering individual infection history in targeting and promoting influenza vaccination is predicted to be a highly effective supplement to the current policy. Our approach can also be generalized for other infectious disease, computer viruses, or ecological networks. PMID:24851863
Baras, Benoit; Bouveret, Nancy; Devaster, Jeanne-Marie; Fries, Louis; Gillard, Paul; Sänger, Roland; Hanon, Emmanuel
Vaccination is considered to be one of the most effective tools to decrease morbidity as well as mortality caused by influenza viruses. For the prevention of seasonal influenza, Fluarix and FluLaval have been marketed since 1987 and 1992, respectively. Both vaccines have consistently been shown to meet or exceed the regulatory criteria for immunogenicity against the three strains H1N1, H3N2 and B, have a good safety profile, and are recommended for vaccinating children and adults of all ages. For the prevention of pandemic influenza, GlaxoSmithKline (GSK) has obtained licensure of a pre-pandemic vaccine, Prepandrix. This split-virus H5N1 adjuvanted with AS03, a proprietary oil-in-water emulsion-based adjuvant system, has demonstrated broad immunity against drifted H5N1 strains and has been shown to be effective in preventing mortality and viral shedding in animal studies. The influenza vaccine portfolio of GSK addresses specific medical needs related to seasonal or pandemic influenza viruses, which remain an important public health threat worldwide.
Schotsaert, Michael; De Filette, Marina; Fiers, Walter; Saelens, Xavier
Influenza vaccines used today are strain specific and need to be adapted every year to try and match the antigenicity of the virus strains that are predicted to cause the next epidemic. The strain specificity of the next pandemic is unpredictable. An attractive alternative approach would be to use a vaccine that matches multiple influenza virus strains, including multiple subtypes. In this review, we focus on the development and clinical potential of a vaccine that is based on the conserved ectodomain of matrix protein 2 (M2) of influenza A virus. Since 1999, a number of studies have demonstrated protection against influenza A virus challenge in animal models using chemical or genetic M2 external domain (M2e) fusion constructs. More recently, Phase I clinical studies have been conducted with M2e vaccine candidates, demonstrating their safety and immunogenicity in humans. Ultimately, and possibly in the near future, efficacy studies in humans should provide proof that this novel vaccine concept can mitigate epidemic and even pandemic influenza A virus infections. PMID:19348565
Schmid, Philipp; Rauber, Dorothee; Betsch, Cornelia; Lidolt, Gianni; Denker, Marie-Luisa
Background Influenza vaccine hesitancy is a significant threat to global efforts to reduce the burden of seasonal and pandemic influenza. Potential barriers of influenza vaccination need to be identified to inform interventions to raise awareness, influenza vaccine acceptance and uptake. Objective This review aims to (1) identify relevant studies and extract individual barriers of seasonal and pandemic influenza vaccination for risk groups and the general public; and (2) map knowledge gaps in understanding influenza vaccine hesitancy to derive directions for further research and inform interventions in this area. Methods Thirteen databases covering the areas of Medicine, Bioscience, Psychology, Sociology and Public Health were searched for peer-reviewed articles published between the years 2005 and 2016. Following the PRISMA approach, 470 articles were selected and analyzed for significant barriers to influenza vaccine uptake or intention. The barriers for different risk groups and flu types were clustered according to a conceptual framework based on the Theory of Planned Behavior and discussed using the 4C model of reasons for non-vaccination. Results Most studies were conducted in the American and European region. Health care personnel (HCP) and the general public were the most studied populations, while parental decisions for children at high risk were under-represented. This study also identifies understudied concepts. A lack of confidence, inconvenience, calculation and complacency were identified to different extents as barriers to influenza vaccine uptake in risk groups. Conclusion Many different psychological, contextual, sociodemographic and physical barriers that are specific to certain risk groups were identified. While most sociodemographic and physical variables may be significantly related to influenza vaccine hesitancy, they cannot be used to explain its emergence or intensity. Psychological determinants were meaningfully related to uptake and should
Olsen, Sonja J.; Mirza, Sara A.; Vonglokham, Phouvanh; Khanthamaly, Viengphone; Chitry, Bounlap; Pholsena, Vathsana; Chitranonh, Visith; Omer, Saad B.; Moen, Ann; Bresee, Joseph S.; Corwin, Andrew; Xeuatvongsa, Anonh
Background Some studies suggest that maternal influenza vaccination can improve birth outcomes. However, there are limited data from tropical settings, particularly Southeast Asia. We conducted an observational study in Laos to assess the effect of influenza vaccination in pregnant women on birth outcomes. Methods We consented and enrolled a cohort of pregnant woman who delivered babies at 3 hospitals during April 2014–February 2015. We collected demographic and clinical information on mother and child. Influenza vaccination status was ascertained by vaccine card. Primary outcomes were the proportion of live births born small for gestational age (SGA) or preterm and mean birth weight. Multivariate models controlled for differences between vaccinated and unvaccinated women and influenza virus circulation. Results We enrolled 5103 women (2172 [43%] were vaccinated). Among the 4854 who had a live birth, vaccinated women were statistically significantly less likely than unvaccinated women to have an infant born preterm during the period of high influenza virus circulation (risk ratio [RR] = 0.56, 95% confidence interval [CI], .45–.70), and the effect remained after adjusting for covariates (adjusted RR, 0.69; 95% CI, .55–.87). There was no effect of vaccine on SGA or mean birth weight. The population-prevented fraction was 18.0%. Conclusions In this observational study, we found indirect evidence of influenza vaccine safety during pregnancy, and women who received vaccine had a reduced risk of delivering a preterm infant during times of high influenza virus circulation. Vaccination may prevent 1 in 5 preterm births that occur during periods of high influenza circulation. PMID:27143672
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Immunogenicity and safety of four different doses of Haemophilus influenzae type b-tetanus toxoid conjugated vaccine, combined with diphtheria-tetanus-pertussis vaccine (DTP-Hib), in Indonesian infants.
Punjabi, Narain H; Richie, Emily L; Simanjuntak, Cyrus H; Harjanto, Sri Juliani; Wangsasaputra, Ferry; Arjoso, Sumarjati; Rofiq, Ainur; Prijanto, Mulyati; Julitasari; Yela, Ursula; Herzog, Christian; Cryz, Stanley J
Widespread use of Haemophilus influenzae type b (Hib) conjugated vaccine in industrialized countries has resulted in a dramatic decline in the incidence of invasive Hib diseases, but the vaccine's cost has prevented its inclusion in basic immunization programs in developing countries. To overcome this problem, combination with diphtheria-tetanus-pertussis (DTP) vaccine or reduction in the dose of Hib vaccine has been proposed. To evaluate the immunogenicity and adverse reactions from lower doses of Hib-polyribosylphosphate (PRP) conjugated with tetanus toxoid (PRP-T), a double-blind study was conducted in Jakarta, Indonesia, and its suburbs. A total of 1048 infants 6 weeks to 6 months of age received three doses of DTP vaccine combined with the usual 10 microg dose or with a reduced dose of 5, 2.5 or 1.25 microg of PRP-T at two-monthly intervals. Antibodies were measured prior to the first dose and 4-6 weeks following the third dose. Adverse reactions were similar among all four groups. The only significant difference was a higher rate of irritability (p<0.02) and of temperature elevation >38 degrees C (p<0.009) after doses 1 and 2 in the lowest dose group (1.25 microg PRP-T) compared to the other groups. All participants tested had a 4-fold increase in antibodies against all DTP antigens. In addition, after a fourth booster dose of Hib, 99.6% of infants produced >or=0.15 microg/ml of antibody to Hib-PRP, and 96.4% showed levels >or=1.0 microg/ml after primary immunization, level that correlate with short- and long-term immunity, respectively. Antibody titers to the PRP antigen showed no significant differences among dosage groups with the exception of the 5.0 microg group, which had a significantly higher GMC than the 1.25 microg group (p<0.012). This study demonstrates that primary vaccination with half, one-fourth, or one-eighth of the usual dose of PRP-T, combined with DTP vaccine, produces protective immune responses, and has side effects that are comparable
This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health. PMID:27489801
Na, Woonsung; Yeom, Minjoo; Yuk, Huijoon; Moon, Hyoungjoon; Kang, Bokyu; Song, Daesub
This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health.
He, Biao; Chang, Haiyan; Liu, Zhihua; Huang, Chaoyang; Liu, Xueying; Zheng, Dan; Fang, Fang; Sun, Bing; Chen, Ze
Vaccination is the best measure to prevent influenza pandemics. Here, we studied the protective effect against heterologous influenza viruses, including A/reassortant/NYMC X-179A (pH1N1), A/Chicken/Henan/12/2004 (H5N1), A/Chicken/Jiangsu/7/2002 (H9N2) and A/Guizhou/54/89×A/PR/8/34 (A/Guizhou-X) (H3N2), in mice first vaccinated with a DNA vaccine of haemagglutinin (HA) or neuraminidase (NA) of A/PR/8/34 (PR8) and then infected with the homologous virus. We showed that PR8 HA or NA vaccination both protected mice against a lethal dose of the homologous virus; PR8 HA or NA DNA vaccination and then PR8 infection in mice offered poor or excellent protection, respectively, against a second, heterologous influenza virus challenge. In addition, before the second heterologous influenza infection, the highest antibody level against nucleoprotein (NP) and matrix (M1 and M2) proteins was found in the PR8 NA-vaccinated and PR8-infected group. The level of induced cellular immunity against NP and M1 showed a trend consistent with that seen in antibody levels. However, PR8 HA+NA vaccination and then PR8 infection resulted in limited protection against heterologous influenza virus challenge. Results of the present study demonstrated that infection of the homologous influenza virus in mice already immunized with a NA vaccine could provide excellent protection against subsequent infection of a heterologous influenza virus. These findings suggested that NA, a major antigen of influenza virus, could be an important candidate antigen for universal influenza vaccines.
Zhang, Xu-Sheng; Pebody, Richard; De Angelis, Daniela; White, Peter J.; Charlett, Andre; McCauley, John W.
Background One pathway through which pandemic influenza strains might emerge is reassortment from coinfection of different influenza A viruses. Seasonal influenza vaccines are designed to target the circulating strains, which intuitively decreases the prevalence of coinfection and the chance of pandemic emergence due to reassortment. However, individual-based analyses on 2009 pandemic influenza show that the previous seasonal vaccination may increase the risk of pandemic A(H1N1) pdm09 infection. In view of pandemic influenza preparedness, it is essential to understand the overall effect of seasonal vaccination on pandemic emergence via reassortment. Methods and Findings In a previous study we applied a population dynamics approach to investigate the effect of infection-induced cross-immunity on reducing such a pandemic risk. Here the model was extended by incorporating vaccination for seasonal influenza to assess its potential role on the pandemic emergence via reassortment and its effect in protecting humans if a pandemic does emerge. The vaccination is assumed to protect against the target strains but only partially against other strains. We find that a universal seasonal vaccine that provides full-spectrum cross-immunity substantially reduces the opportunity of pandemic emergence. However, our results show that such effectiveness depends on the strength of infection-induced cross-immunity against any novel reassortant strain. If it is weak, the vaccine that induces cross-immunity strongly against non-target resident strains but weakly against novel reassortant strains, can further depress the pandemic emergence; if it is very strong, the same kind of vaccine increases the probability of pandemic emergence. Conclusions Two types of vaccines are available: inactivated and live attenuated, only live attenuated vaccines can induce heterosubtypic immunity. Current vaccines are effective in controlling circulating strains; they cannot always help restrain pandemic
Hu, Weibin; Zhang, Hong; Han, Qinglin; Li, Li; Chen, Yixin; Xia, Ningshao; Chen, Ze; Shu, Yuelong; Xu, Ke; Sun, Bing
A cell culture-based vaccine production system is preferred for the large-scale production of influenza vaccines and has advantages for generating vaccines against highly pathogenic influenza A viruses. Vero cells have been widely used in human vaccine manufacturing, and the safety of these cells has been well demonstrated. However, the most commonly used influenza-vaccine donor virus, A/Puerto Rico/8/1934 (PR8) virus, does not grow efficiently in Vero cells. Therefore, we adapted the PR8 virus to Vero cells by continuous passaging, and a high-growth strain was obtained after 20 passages. Sequence analysis and virological assays of the adapted strain revealed that mutations in four viral internal genes (NP, PB1, PA and NS1) were sufficient for adaptation. The recombinant virus harboring these mutations (PR8-4mut) displayed accelerated viral transport into the nucleus and increased RNP activity. Importantly, the PR8-4mut could serve as a backbone donor virus to support the growth of the H7N1, H9N2 and H5N1 avian viruses and the H1N1 and H3N2 human viruses in Vero cells without changing its pathogenicity in either chicken embryos or mice. Thus, our work describes the generation of a Vero-adapted, high-yield PR8-4mut virus that may serve as a promising candidate for an influenza-vaccine donor virus.
Martínez-Baz, Iván; Navascués, Ana; Pozo, Francisco; Chamorro, Judith; Albeniz, Esther; Casado, Itziar; Reina, Gabriel; Cenoz, Manuel García; Ezpeleta, Carmen; Castilla, Jesús
Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent laboratory-confirmed influenza B cases are uncommon, and few have analyzed the effect in preventing hospitalized cases. We have evaluated the influenza VE in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012–2013 season, which was dominated by a vaccine-matched influenza B virus. In the population covered by the Navarra Health Service, all hospitalized patients with influenza-like illness (ILI) and all ILI patients attended by a sentinel network of general practitioners were swabbed for influenza testing, and all were included in a test-negative case-control analysis. VE was calculated as (1-odds ratio)×100. Among 744 patients tested, 382 (51%) were positive for influenza virus: 70% for influenza B, 24% for A(H1N1)pdm09, and 5% for A(H3N2). The overall estimate of VE in preventing laboratory-confirmed influenza was 63% (95% confidence interval (CI): 34 to 79), 55% (1 to 80) in outpatients and 74% (33 to 90) in hospitalized patients. The VE was 70% (41 to 85) against influenza B and 43% (−45 to 78) against influenza A. The VE against virus B was 87% (52 to 96) in hospitalized patients and 56% in outpatients (−5 to 81). Adjusted comparison of vaccination status between inpatient and outpatient cases with influenza B did not show statistically significant differences (odds ratio: 1.13; p = 0.878). These results suggest a high protective effect of the vaccine in the 2012–2013 season, with no differences found for the effect between outpatient and hospitalized cases. PMID:25996366
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Kunze, Ursula; Kunze, Michael
This paper describes a paradoxical situation in Austria. The vaccination rate against tick-borne encephalitis (TBE) in the general population is 82%, which is the highest worldwide, whereas the vaccination rate against influenza is about 8% and is among the lowest worldwide. A high awareness of TBE among the Austrian population achieved by an annual social marketing programme and the wide use of effective and well-tolerated vaccines have led to a successful containment of that disease. The vaccination coverage increased from 6% in 1980 to 82% in 2013 and exceeds 90% in some high-risk areas. This has led to a steady decline in the number of TBE cases from several hundred cases to 50 to 100 cases per year. The situation in regard to influenza vaccination is the opposite. Although Austria has issued one of the most extensive recommendations for influenza vaccination worldwide, the vaccination rate of the general population is extremely low. The possible reasons for the failure in the implementation of recommendations are ignorance, lack of social marketing and the predominance of a distinct discordance within the health system in general, and the Austrian medical fraternity in particular.
de Perio, Marie A.; Wiegand, Douglas M.; Brueck, Scott E.
Background: Influenza can spread among students, teachers, and staff in school settings. Vaccination is the most effective method to prevent influenza. We determined 2012-2013 influenza vaccination coverage among school employees, assessed knowledge and attitudes regarding the vaccine, and determined factors associated with vaccine receipt.…
... Influenza Vaccination Week, 2010 8615 Proclamation 8615 Presidential Documents Proclamations Proclamation 8615 of December 7, 2010 Proc. 8615 National Influenza Vaccination Week, 2010By the President of the... National Influenza Vaccination Week, we remind all Americans that the flu vaccine is safe and effective...
Greenberg, David P; Robertson, Corwin A; Gordon, Daniel M
Influenza and dengue are viral illnesses of global public health importance, especially among children. Accordingly, these diseases have been the focus of efforts to improve their prevention and control. Influenza vaccination offers the best protection against clinical disease caused by strains contained within the specific year's formulation. It is not uncommon for there to be a mismatch between vaccine strains and circulating strains, particularly with regards to the B lineages. For more than a decade, two distinct lineages of influenza B (Yamagata and Victoria) have co-circulated in the US with varying frequencies, but trivalent influenza vaccines contain only one B-lineage strain and do not offer adequate protection against the alternate B-lineage. Quadrivalent influenza vaccines (QIVs), containing two A strains (H1N1 and H3N2) and two B strains (one from each lineage) have been developed to help protect against the four strains predicted to be the most likely to be circulating. The QIV section of this article discusses epidemiology of pediatric influenza, importance of influenza B in children, potential benefits of QIV, and new quadrivalent vaccines. In contrast to influenza, a vaccine against dengue is not yet available in spite of many decades of research and development. A global increase in reports of dengue fever (DF) and its more severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), suggest that US physicians will increasingly encounter patients with this disease. Similarities of the early signs and symptoms of influenza and dengue and the differences in disease management necessitates a better understanding of the epidemiology, clinical presentation, management, and prevention of DF by US physicians, including pediatricians. The article also provides a brief overview of dengue and discusses dengue vaccine development.
Castro, Breno Augusto Campos de; Pereira, Juliana Milagres Macedo; Meyer, Renata Leal Bregunci; Trindade, Fernanda Marques; Pedrosa, Moises Salgado; Piancastelli, André Costa Cruz
The etiology of pityriasis lichenoides is unknown. One of the accepted theories admits that PL is an inflammatory response to extrinsic antigens such as infectious agents, drugs and vaccines. In recent medical literature, only the MMR vaccine (Measles, Mumps and Rubella) was associated with the occurrence of this disease. We present a case of a male, 12 year old healthy patient who, five days after Influenza vaccination, developed erythematous papules on the trunk, abdomen and limbs, some with adherent crusts and associated systemic symptoms. This case report is notable for describing the first case of pityriasis lichenoides et varioliformis acuta associated with the vaccine against Influenza.
Mistilis, Matthew J; Bommarius, Andreas S; Prausnitz, Mark R
The goal of this study is to develop thermostable microneedle patch formulations for influenza vaccine that can be partially or completely removed from the cold chain. During vaccine drying associated with microneedle patch manufacturing, ammonium acetate and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane (PDMS) led to increased stability compared with drying on stainless steel. A number of excipients, mostly polysaccharides and some amino acids, further stabilized the influenza vaccine during drying. Over longer time scales of storage, combinations of stabilizers preserved the most vaccine activity. Finally, dissolving microneedle patches formulated with arginine and calcium heptagluconate had no significant activity loss for all three strains of seasonal influenza vaccine during storage at room temperature for 6 months. We conclude that appropriately formulated microneedle patches can exhibit remarkable thermostability that could enable storage and distribution of influenza vaccine outside the cold chain.
Travers, Jasmine L; Stone, Patricia W; Bjarnadottir, Ragnhildur I; Pogorzelska-Maziarz, Monika; Castle, Nicholas G; Herzig, Carolyn T A
Influenza vaccination remains the cornerstone of influenza prevention, yet national goals for nursing home residents and staff vaccination have not been met. Few studies have examined associations between facility and resident characteristics; employee processes, such as staff vaccination policies; and resident influenza vaccination. In this national survey of nursing homes, employee processes were not associated with resident influenza vaccination; however, various facility and resident characteristics were.
Plantet, Claire; Sanchez, Stéphane; Cohen, Nadia; Denormandie, Philippe; Dinh, Aurélien
Influenza epidemics in nursing homes can lead to serious complications with a high level of lethality. It has been shown that an active policy of awareness campaigns with obligatory information materials and easy access to influenza immunisation increases the rate of vaccination coverage.
Seasonal influenza is a significant cause of morbidity and mortality of children in Korea. However, few data are available on parental perception and action toward childhood influenza. This study aimed to characterize parental perception and patterns of action in response to influenza and influenza-like illnesses (ILIs), including vaccination and healthcare use. This prospective study involved a random survey of parents whose children were aged 6–59 months. The survey was conducted in October 2014. The study included 638 parents of 824 children younger than 6 years. Most parental information of influenza came from mass media (28.2%) and social media (15.5%). The factor that most often motivated parents to vaccinate their children against influenza was promotion of the government or mass media (36.6%). Negative predictors of immunization included safety concerns about influenza vaccination (28.1%) and mistrust in the vaccine's effectiveness (23.3%). Therefore, correct information about influenza and vaccination from mass media will be one of the cornerstones for implementing a successful childhood immunization program and reducing morbidity and mortality in Korea. Furthermore, to enroll younger children in vaccination programs, and to minimize coverage gaps, public concerns about vaccine safety should be resolved. The demographic data in the present study will be used to provide a deeper insight into a parental perception and will help health care providers increase influenza immunization rate. PMID:28049230
Luke, Catherine J; Subbarao, Kanta
A variety of platforms are being explored for the development of vaccines for pandemic influenza. Observations that traditional inactivated subvirion vaccines and live-attenuated vaccines against H5 and some H7 influenza viruses were poorly immunogenic spurred efforts to evaluate new approaches, including whole virus vaccines, higher doses of antigen, addition of adjuvants and combinations of different vaccine modalities in heterologous prime-boost regimens to potentiate immune responses. Results from clinical trials of prime-boost regimens have been very promising. Further studies are needed to determine optimal combinations of platforms, intervals between doses of vaccines and the logistics of deployment in pre-pandemic and early pandemic settings.
Novati, R; Nebiolo, P E; Galotto, C; Mastaglia, M; Manes, M
A fifty-three years old surgeon had acute renal failure consisting with acute tubulo-interstizial nephropaty twelve days after influenza vaccination; he was on statin therapy since one month. He was given steroidal therapy and fully recovered two weeks apart. This is the fourth case report of acute renal failure after influenza vaccination in patients on statins therapy. The case we describe could account for a underestimated, even if very rare, phenomenon.
Cox, Manon M. J.
Pandemic influenza has become a high priority item for all public health authorities. An influenza pandemic is believed to be imminent, and scientists agree that it will be a matter of when, where, and what will be the causative agent. Recently, most attention has been directed to human cases of avian influenza caused by a H5N1 avian influenza virus. An effective vaccine will be needed to substantially reduce the impact of an influenza pandemic. Current influenza vaccine manufacturing technology is not adequate to support vaccine production in the event of an avian influenza outbreak, and it has now become clear that new innovative production technology is required. Antiviral drugs, on the other hand, can play a very important role in slowing the disease spread but are in short supply and resistance has been a major issue. Here, we provide an update on the status of pandemic vaccine development and antiviral drugs. Finally, we conclude with some proposed areas of focus in pandemic vaccine preparedness. PMID:17132338
Romagosa, Anna; Allerson, Matt; Gramer, Marie; Joo, Han Soo; Deen, John; Detmer, Susan; Torremorell, Montserrat
Limited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R) of infection (i.e. the number of secondary infections caused by an infectious individual) using a deterministic Susceptible-Infectious-Recovered (SIR) model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i) non-vaccinated (NV), (ii) vaccinated with a heterologous vaccine (HE), and (iii) vaccinated with a homologous inactivated vaccine (HO). The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference between R estimates was observed between vaccinated and non-vaccinated pigs (p < 0.05). A statistically significant reduction in transmission was observed in the vaccinated groups where R (95%CI) was 1 (0.39-2.09) and 0 for the HE and the HO groups respectively, compared to an Ro value of 10.66 (6.57-16.46) in NV pigs (p < 0.05). Transmission in the HE group was delayed and variable when compared to the NV group and transmission could not be detected in the HO group. Results from this study indicate that influenza vaccines can be used to decrease susceptibility to influenza infection and decrease influenza transmission.
Song, Joon Young; Cheong, Hee Jin; Lee, Jacob; Wie, Seong-Heon; Park, Kyung-Hwa; Kee, Sae Yoon; Jeong, Hye Won; Kim, Yeon-Sook; Noh, Ji Yun; Choi, Won Suk; Park, Dae Won; Sohn, Jang Wook; Kim, Woo Joo
Influenza vaccines are the primary method for preventing influenza and its complications. Considering the increasing demand for influenza vaccines, vaccine manufacturers are required to establish large-scale production systems. This phase IV randomized trial was conducted to evaluate the lot consistency of trivalent split influenza vaccines regarding immunogenicity and safety. A total of 1,023 healthy adults aged 18-64 y were enrolled in the study. Subjects were randomly assigned in a 1:1 ratio to receive the GC FLU® Prefilled Syringe or the GC FLU® Injection, and they were further randomized to one of 3 lots of each vaccine in a 1:1:1 ratio. In both GC FLU® Injection and GC FLU® Prefilled Syringe groups, immune responses were equivalent between lots for each of the 3 vaccine strains on day 21. The 2-sided 95% CI of GMT ratios between pairs of lots were between 0.67 and 1.5, meeting the equivalence criteria. After vaccination, all 3 criteria of the European Medicines Agency were met in both GC FLU® Injection and GC FLU® Prefilled Syringe groups. The vaccines showed tolerable safety profiles without serious adverse events. The demonstration of lot consistency, robust immunogenic responses and favorable safety profiles support the reliability of mass-manufacturing systems for the GC FLU® Injection and GC FLU® Prefilled Syringe.
Tsen, Shaw-Wei David; Donthi, Nisha; La, Victor; Hsieh, Wen-Han; Li, Yen-Der; Knoff, Jayne; Chen, Alexander; Wu, Tzyy-Choou; Hung, Chien-Fu; Achilefu, Samuel; Tsen, Kong-Thon
Abstract. There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques. PMID:25423046
Tsen, Shaw-Wei David; Donthi, Nisha; La, Victor; Hsieh, Wen-Han; Li, Yen-Der; Knoff, Jayne; Chen, Alexander; Wu, Tzyy-Choou; Hung, Chien-Fu; Achilefu, Samuel; Tsen, Kong-Thon
There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.
Grødeland, Gunnveig; Bogen, Bjarne
There are two major limitations to vaccine preparedness in the event of devastating influenza pandemics: the time needed to generate a vaccine and rapid generation of sufficient amounts. DNA vaccination could represent a solution to these problems, but efficacy needs to be enhanced. In a separate line of research, it has been established that targeting of vaccine molecules to antigen-presenting cells enhances immune responses. We have combined the two principles by constructing DNA vaccines that encode bivalent fusion proteins; these target hemagglutinin to MHC class II molecules on antigen-presenting cells. Such DNA vaccines rapidly induce hemagglutinin-specific antibodies and T cell responses in immunized mice. Responses are long-lasting and protect mice against challenge with influenza virus. In a pandemic situation, targeted DNA vaccines could be produced and tested within a month. The novel DNA vaccines could represent a solution to pandemic preparedness in the advent of novel influenza pandemics.
Gamoh, Koichiro; Nakamura, Shigeyuki
The basic countermeasures used to control highly pathogenic avian influenza (HPAI) are early detection procedures and the culling of affected chickens. However, if successive HPAI outbreaks occur, the vaccination may be an option for controlling HPAI. Therefore, avian influenza (AI) vaccines are stocked by the Japanese government. By contrast, equine influenza (EI) vaccine is an effective tool for preventing or controlling EI. Because antigenic drifts affect the efficacy of AI and EI vaccines, the vaccine strains should be updated rapidly. However, the development and registration of veterinary vaccines usually takes several years. In response to this issue, the Ministry of Agriculture, Forestry, and Fisheries (MAFF) established a system that allows AI and EI vaccine strains to be updated rapidly. National Veterinary Assay Laboratory, MAFF, established a vaccine strains selection committee for veterinary influenza vaccine. The main agendas involve determining whether the current vaccine strains need to be updated and selecting the most appropriate vaccine strains. The committee concluded that A/duck/Hokkaido/Vac-3/2007(H5N1) was added to the strains of stockpiled AI vaccines and that the EI vaccine strains did not need to be changed, but that the clade 2 viruses of the Florida sub-lineage strain, A/equine/Yokohama/aq13/2010(H3N8) was added to the EI vaccine strain.
Nakaya, Helder I; Wrammert, Jens; Lee, Eva K; Racioppi, Luigi; Marie-Kunze, Stephanie; Haining, W. Nicholas; Means, Anthony R; Kasturi, Sudhir P; Khan, Nooruddin; Li, Gui-Mei; McCausland, Megan; Kanchan, Vibhu; Kokko, Kenneth E; Li, Shuzhao; Elbein, Rivka; Mehta, Aneesh K; Aderem, Alan; Subbarao, Kanta; Ahmed, Rafi; Pulendran, Bali
We used a systems biological approach to study innate and adaptive responses to influenza vaccination in humans, during 3 consecutive influenza seasons. Healthy adults were vaccinated with inactivated (TIV) or live attenuated (LAIV) influenza vaccines. TIV induced greater antibody titers and enhanced numbers of plasmablasts than LAIV. In TIV vaccinees, early molecular signatures correlated with, and accurately predicted, later antibody titers in two independent trials. Interestingly, the expression of Calcium/calmodulin-dependent kinase IV (CamkIV) at day 3 was inversely correlated with later antibody titers. Vaccination of CamkIV −/− mice with TIV induced enhanced antigen-specific antibody titers, demonstrating an unappreciated role for CaMKIV in the regulation of antibody responses. Thus systems approaches can predict immunogenicity, and reveal new mechanistic insights about vaccines. PMID:21743478
Shen, Zhenwei; Lei, Han
Human β-defensin-2 (hBD-2) is an antimicrobial peptide with high activity and broad spectrum activity. hBD-2 expression may be highly elevated by microorganisms and inflammation. We reported that the majority of common vaccines used, including 23-valent pneumococcal polysaccharide vaccine, Haemophilus influenzae type b vaccine and split influenza virus vaccine, could induce the expression of hBD-2 in epithelial cells. Among them, the 23-valent pneumococcal polysaccharide vaccine was effective at a lower concentration (0.5 µg/ml), while Haemophilus influenzae type b vaccine and split influenza virus vaccine were effective at the concentration of 1 µg/ml. However, bacteriostatic experiments revealed that the split influenza virus vaccine was capable of inducing the highest antimicrobial activity. The medium of the 23-valent pneumococcal polysaccharide vaccine treatment group had a higher antimicrobial activity than the medium of the Haemophilus influenzae type b vaccine treatment group. The transcriptional regulator of hBD-2, that is, the NF-κB subunit, had a high level of activity, while the normal epithelial cells showed barely detectable activity, indicating that these vaccines have potential for clinical application.
Gill, Harvinder S; Kang, Sang-Moo; Quan, Fu-Shi; Compans, Richard W
Introduction Most vaccines are administered by intramuscular injection using a hypodermic needle and syringe. Some limitations of this procedure include reluctance to be immunized because of fear of needlesticks, and concerns associated with the safe disposal of needles after their use. Skin delivery is an alternate route of vaccination that has potential to be painless and could even lead to dose reduction of vaccines. Recently, microneedles have emerged as a novel painless approach for delivery of influenza vaccines via the skin. Areas covered In this review, we briefly summarize the approaches and devices used for skin vaccination, and then focus on studies of skin immunization with influenza vaccines using microneedles. We discuss both the functional immune response and the nature of this immune response following vaccination with microneedles. Expert opinion The cutaneous administration of influenza vaccines using microneedles offers several advantages: it is painless, elicits stronger immune responses in preclinical studies and could improve responses in high-risk populations. These dry formulations of vaccines provide enhanced stability, a property of high importance in enabling their rapid global distribution in response to possible outbreaks of pandemic influenza and newly emerging infectious diseases. PMID:24521050
Li, Chengjun; Bu, Zhigao; Chen, Hualan
H5N1 avian influenza viruses (AIVs) have spread widely to more than 60 countries spanning three continents. To control the disease, vaccination of poultry is implemented in many of the affected countries, especially in those where H5N1 viruses have become enzootic in poultry and wild birds. Recently, considerable progress has been made toward the development of novel avian influenza (AI) vaccines, especially recombinant virus vector vaccines and DNA vaccines. Here, we will discuss the recent advances in vaccine development and use against H5N1 AIV in poultry. Understanding the properties of the available, novel vaccines will allow for the establishment of rational vaccination protocols, which in turn will help the effective control and prevention of H5N1 AI.
Grijalva, Carlos G.; Zhu, Yuwei; Williams, Derek J.; Self, Wesley H.; Ampofo, Krow; Pavia, Andrew T.; Stockmann, Chris R.; McCullers, Jonathan; Arnold, Sandra R.; Wunderink, Richard G.; Anderson, Evan J.; Lindstrom, Stephen; Fry, Alicia M.; Foppa, Ivo M.; Finelli, Lyn; Bramley, Anna M.; Jain, Seema; Griffin, Marie R.; Edwards, Kathryn M.
Importance Few studies have evaluated the relationship between influenza vaccination and pneumonia, a serious complication of influenza infection. Objective Assess the association between influenza vaccination status and hospitalization for community-acquired laboratory-confirmed influenza pneumonia. Design, Setting and Participants The Etiology of Pneumonia in the Community (EPIC) study was a prospective observational multicenter study of hospitalizations for community-acquired pneumonia conducted from January 2010 through June 2012 in four US sites. We used EPIC study data from patients ≥6 months of age with laboratory-confirmed influenza infection and verified vaccination status during the influenza seasons, and excluded patients with recent hospitalization, from chronic care residential facilities, and with severe immunosuppression. Logistic regression was used to calculate odds ratios, comparing the odds of vaccination between influenza-positive (cases) and influenza-negative (controls) pneumonia patients, controlling for demographics, co-morbidities, season, study site and timing of disease onset. Vaccine effectiveness was estimated as (1-odds ratio) × 100%. Exposure Influenza vaccination, verified through record review. Outcome Influenza pneumonia, confirmed by real-time reverse transcription-polymerase chain reaction performed on nasal/oropharyngeal swabs. Results Overall, 2767 patients hospitalized for pneumonia were eligible for the study; 162 (5.9%) were influenza positive. Twenty-eight (17%) of 162 cases with influenza-associated pneumonia and 766 (29%) of 2605 controls with influenza-negative pneumonia had been vaccinated. The adjusted odds ratio of prior influenza vaccination between cases and controls was 0.43 (95% CI 0.28–0.68 [estimated vaccine effectiveness 56.7% (95% CI 31.9–72.5)]). Conclusions and relevance Among children and adults hospitalized with community-acquired pneumonia, those with laboratory confirmed influenza
Swayne, David E
Avian influenza vaccines for poultry are based on hemagglutinin proteins, and protection is specific to the vaccine subtype. Over 113 billion doses have been used between 2002 and 2010 for high pathogenicity avian influenza control. No universal vaccines are currently available. The majority of avian influenza vaccines are inactivated whole influenza viruses that are grown in embryonating eggs, inactivated, emulsified in oil adjuvant systems, and injected into chickens. Live virus-vectored vaccines such as recombinant viruses of fowl pox, Newcastle disease, herpesvirus of turkeys and duck enteritis containing inserts of avian influenza virus hemagglutinin genes have been used on a more limited basis. In studies to evaluate vaccine efficacy and potency, the protocol design and its implementation should address the biosafety level needed for the work, provide information required for approval by Institutional Biosafety and Animal Care Committees, contain information on seed strain selection, provide needed information on animal subjects and their relevant parameters, and address the selection and use of challenge viruses. Various metrics have been used to directly measure vaccine induced protection. These include prevention of death, clinical signs, and lesions; prevention of decreases in egg production and alterations in egg quality; quantification of the reduction in virus replication and shedding from the respiratory tract and gastrointestinal tracts; and prevention of contact transmission in in vivo poultry experiments. In addition, indirect measures of vaccine potency and protection can be developed and validated against the direct measures and include serological assays in vaccinated poultry and assessment of the content of hemagglutinin antigen in the vaccine. These indirect assessments of protection are useful in determining if vaccine batches have a consistent ability to protect. For adequate potency, vaccines should contain 50 mean protective doses of
Rodríguez-Fernández, R; Martínez-López, A B; Pérez-Moreno, J; González-Sánchez, M I; González-Martínez, F; Hernández-Sampelayo, T; Mejias, A
Influenza vaccination has been shown to be the most effective preventive strategy to reduce influenza-related morbidity and mortality in high-risk groups. Despite healthcare personnel (HCP) being considered part of such high-risk groups, their vaccination coverage is low in Europe. In January 2012, we distributed an 18-question survey regarding influenza vaccination to HCP at Gregorio Marañon Paediatric Hospital, in Madrid, Spain. After we documented that only ~30% of HCP were vaccinated an educational programme was implemented in October 2012 before the next influenza season. In January 2013, the same survey delivered again to all HCP documented a significant increase in vaccination rates (from 30% to 40%, P = 0·007) mainly among physicians and for patients' protection. In summary we found that a simple and inexpensive educational programme significantly improved the uptake of influenza vaccination in HCP in our centre. Nevertheless, vaccination rates remained low, and broader and updated campaigns are needed to overcome perception barriers.
Hamidi, Ahd; Verdijk, Pauline; Kreeftenberg, Hans
Introduction of Haemophilus influenzae type b (Hib) vaccine in low- and middle-income countries has been limited by cost and availability of Hib conjugate vaccines for a long time. It was previously recognized by the Institute for Translational Vaccinology (Intravacc, originating from the former Vaccinology Unit of the National Institute of Public Health [RIVM] and the Netherlands Vaccine Institute [NVI]) that local production of a Hib conjugate vaccine would increase the affordability and sustainability of the vaccine and thereby help to speed up Hib introduction in these countries. A new affordable and a non-infringing production process for a Hib conjugate vaccine was developed, including relevant quality control tests, and the technology was transferred to a number of vaccine manufacturers in India, Indonesia, and China. As part of the Hib technology transfer project managed by Intravacc, a preclinical toxicity study was conducted in the Netherlands to test the safety and immunogenicity of this new Hib conjugate vaccine. The data generated by this study were used by the technology transfer partners to accelerate the clinical development of the new Hib conjugate vaccine. A repeated dose toxicity and local tolerance study in rats was performed to assess the reactogenicity and immunogenicity of a new Hib conjugate vaccine compared to a licensed vaccine. The results showed that the vaccine was well tolerated and immunogenic in rats, no major differences in both safety and immunogenicity in rats were found between the vaccine produced according to the production process developed by Intravacc and the licensed one. Rats may be useful to verify the immunogenicity of Hib conjugate vaccines and for preclinical evaluation. In general, nonclinical evaluation of the new Hib conjugate vaccine, including this proof of concept (safety and immunogenicity study in rats), made it possible for technology transfer partners, having implemented the original process with no changes
Hamidi, Ahd; Verdijk, Pauline; Kreeftenberg, Hans
Introduction of Haemophilus influenzae type b (Hib) vaccine in low- and middle-income countries has been limited by cost and availability of Hib conjugate vaccines for a long time. It was previously recognized by the Institute for Translational Vaccinology (Intravacc, originating from the former Vaccinology Unit of the National Institute of Public Health [RIVM] and the Netherlands Vaccine Institute [NVI]) that local production of a Hib conjugate vaccine would increase the affordability and sustainability of the vaccine and thereby help to speed up Hib introduction in these countries. A new affordable and a non-infringing production process for a Hib conjugate vaccine was developed, including relevant quality control tests, and the technology was transferred to a number of vaccine manufacturers in India, Indonesia, and China. As part of the Hib technology transfer project managed by Intravacc, a preclinical toxicity study was conducted in the Netherlands to test the safety and immunogenicity of this new Hib conjugate vaccine. The data generated by this study were used by the technology transfer partners to accelerate the clinical development of the new Hib conjugate vaccine. A repeated dose toxicity and local tolerance study in rats was performed to assess the reactogenicity and immunogenicity of a new Hib conjugate vaccine compared to a licensed vaccine. The results showed that the vaccine was well tolerated and immunogenic in rats, no major differences in both safety and immunogenicity in rats were found between the vaccine produced according to the production process developed by Intravacc and the licensed one. Rats may be useful to verify the immunogenicity of Hib conjugate vaccines and for preclinical evaluation. In general, nonclinical evaluation of the new Hib conjugate vaccine, including this proof of concept (safety and immunogenicity study in rats), made it possible for technology transfer partners, having implemented the original process with no changes
Background Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. Methods Surveillance of respiratory viruses was conducted in JIA patients during ARI season (March to August) in two consecutive years: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. Results During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. Conclusion ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients. PMID:23510667
Black, Carla L; Yue, Xin; Ball, Sarah W; Donahue, Sara M A; Izrael, David; de Perio, Marie A; Laney, A Scott; Williams, Walter W; Lindley, Megan C; Graitcer, Samuel B; Lu, Peng-Jun; DiSogra, Charles; Devlin, Rebecca; Walker, Deborah K; Greby, Stacie M
The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all health care personnel to reduce influenza-related morbidity and mortality among both health care personnel and their patients (1-4). To estimate influenza vaccination coverage among U.S. health care personnel for the 2015-16 influenza season, CDC conducted an opt-in Internet panel survey of 2,258 health care personnel during March 28-April 14, 2016. Overall, 79.0% of survey participants reported receiving an influenza vaccination during the 2015-16 season, similar to the 77.3% coverage reported for the 2014-15 season (5). Coverage in long-term care settings increased by 5.3 percentage points compared with the previous season. Vaccination coverage continued to be higher among health care personnel working in hospitals (91.2%) and lower among health care personnel working in ambulatory (79.8%) and long-term care settings (69.2%). Coverage continued to be highest among physicians (95.6%) and lowest among assistants and aides (64.1%), and highest overall among health care personnel who were required by their employer to be vaccinated (96.5%). Among health care personnel working in settings where vaccination was neither required, promoted, nor offered onsite, vaccination coverage continued to be low (44.9%). An increased percentage of health care personnel reporting a vaccination requirement or onsite vaccination availability compared with earlier influenza seasons might have contributed to the overall increase in vaccination coverage during the past 6 influenza seasons.
In response to the influenza vaccine shortage in the United States, the Connecticut Department of Public Health (DPH) operated a telephone hotline during October 22, 2004-January 15, 2005. The purpose of the hotline was to address questions from the public regarding the availability of influenza vaccine, reduce the number of telephone inquiries to physicians and local health departments (LHDs), and advise callers regarding which groups were most at risk and in need of influenza vaccination. Caller information was collected and shared daily with LHDs, which were encouraged to follow up with callers as their resources allowed. This report summarizes results of a retrospective survey of callers to the DPH influenza vaccine hotline during November 2004. The results indicated that vaccination coverage varied by age group and that persons receiving follow-up calls from LHDs were more likely to receive vaccination. State health departments might consider a hotline as a method for educating the public regarding influenza vaccination and a follow-up system as a means to improve vaccination coverage, especially among those at greatest risk.
The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV),...
Galvao, Tais F.; Silva, Marcus T.; Zimmermann, Ivan R.; Lopes, Luiz Antonio B.; Bernardo, Eneida F.; Pereira, Mauricio G.
Objective. To assess the effects of the inactivated influenza virus vaccine on influenza outcomes in pregnant women and their infants. Methods. We performed a systematic review of the literature. We searched for randomized controlled trials and cohort studies in the MEDLINE, Embase, and other relevant databases (inception to September 2013). Two researchers selected studies and extracted the data independently. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the quality of the evidence. Results. We included eight studies out of 1,967 retrieved records. Influenza vaccination in pregnant women significantly reduced the incidence of influenza-like illness in mothers and their infants when compared with control groups (high-quality evidence) and reduced the incidence of laboratory-confirmed influenza in infants (moderate-quality evidence). No difference was found with regard to influenza-like illness with fever higher than 38°C (moderate-quality evidence) or upper respiratory infection (very-low-quality evidence) in mothers and infants. Conclusions. Maternal vaccination against influenza was shown to prevent influenza-like illness in women and infants; no differences were found for other outcomes. As the quality of evidence was not high overall, further research is needed to increase confidence and could possibly change these estimates. PMID:24971194
Stewart, Alexandra M; Cox, Marisa A
Nosocomial influenza outbreaks, attributed to the unvaccinated health care workforce, have contributed to patient complications or death, worker illness and absenteeism, and increased economic costs to the health care system. Since 1981, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has recommended that all HCP receive an annual influenza vaccination. Health care employers (HCE) have adopted various strategies to encourage health care personnel (HCP) to voluntarily receive influenza vaccination, including: sponsoring educational and promotional campaigns, increasing access to seasonal influenza vaccine, permitting the use of declination statements, and combining multiple approaches. However, these measures failed to significantly increase uptake among HCP. As a result, beginning in 2004, health care facilities and local health departments began to require certain HCP to receive influenza vaccination as a condition of employment and annually. Today, hundreds of facilities throughout the country have developed and implemented similar policies. Mandatory vaccination programs have been endorsed by professional and non-profit organizations, state health departments, and public health. These programs have been more effective at increasing coverage rates than any voluntary strategy, with some health systems reporting coverage rates up to 99.3%. Several states have enacted laws requiring HCEs to implement vaccination programs for the workforce. These laws present an example of how states will respond to threats to the public's health and constrain personal choice in order to protect vulnerable populations. This study analyzes laws in twenty states that address influenza vaccination requirements for HCP who practice in acute or long-term care facilities in the United States. The laws vary in the extent to which they incorporate the six elements of a mandatory HCP influenza vaccination program. Four of the
Cook, Ian F
A 76-year-old male presented with subacromial/subdeltoid bursitis following influenza vaccine administration into the left deltoid muscle. This shoulder injury related to vaccine administration (SIRVA) could have been prevented by the use of a safe, evidence based protocol for the intramuscular injection of the deltoid muscle.
Salk, Jonas; Salk, Darrell
Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)
Cook, Ian F
A 76-year-old male presented with subacromial/subdeltoid bursitis following influenza vaccine administration into the left deltoid muscle. This shoulder injury related to vaccine administration (SIRVA) could have been prevented by the use of a safe, evidence based protocol for the intramuscular injection of the deltoid muscle. PMID:24284281
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…
Kidd, Francine; Wones, Robert; Momper, Adam; Bechtle, Mavis; Lewis, Margaret
We believe we are the first union hospital to succeed in mandating the seasonal influenza vaccine for employees and physicians. We relate the process that we used to achieve this success. Our main purpose is to share our success with other colleagues in the health care industry who are facing similar opposition to mandatory vaccination.
Ahmed, S. Sohail; Steinman, Lawrence
ABSTRACT We previously reported an increased frequency of antibodies to hypocretin (HCRT) receptor 2 in sera obtained from narcoleptic patients who received the European AS03-adjuvanted vaccine Pandemrix (GlaxoSmithKline Biologicals, s.a.) for the global influenza A H1N1 pandemic in 2009 [A(H1N1)pdm09]. These antibodies cross-reacted with a particular fragment of influenza nucleoprotein (NP) – one of the proteins naturally contained in the virus used to make seasonal influenza vaccine and pandemic influenza vaccines. The purpose of this commentary is to provide additional insights and interpretations of the findings and share additional data not presented in the original paper to help the reader appreciate the key messages of that publication. First, a brief background to narcolepsy and vaccine-induced narcolepsy will be provided. Then, additional insights and clarification will be provided on the following topics: 1) the critical difference identified in the adjuvanted A(H1N1)pdm09 vaccines, 2) the contributing factor likely for the discordant association of narcolepsy between the AS03-adjuvanted pandemic vaccines Pandemrix and Arepanrix (GlaxoSmithKline Biologicals, s.a.), 3) the significance of detecting HCRT receptor 2 (HCRTr2) antibodies in some Finnish control subjects, 4) the approach used for the detection of HCRTr2 antibodies in vaccine-associated narcolepsy, and 5) the plausibility of the proposed mechanism involving HCRTr2 modulation in vaccine-associated narcolepsy. PMID:27031682
... taken in its entirety from the CDC Inactivated Influenza Vaccine Information Statement (VIS) www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.html CDC review information for Inactivated Influenza VIS: ...
... entirety from the CDC Hib (Haemophilus Influenzae Type b) Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... CDC review information for Hib (Haemophilus Influenzae Type b) VIS: Page last reviewed: April 2, 2015 Page ...
Huang, Qiu Sue; Turner, Nikki; Baker, Michael G; Williamson, Deborah A; Wong, Conroy; Webby, Richard; Widdowson, Marc-Alain
The 2009 influenza A(H1N1)pdm09 pandemic highlighted the need for improved scientific knowledge to support better pandemic preparedness and seasonal influenza control. The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project, a 5-year (2012-2016) multiagency and multidisciplinary collaboration, aimed to measure disease burden, epidemiology, aetiology, risk factors, immunology, effectiveness of vaccination and other prevention strategies for influenza and other respiratory infectious diseases of public health importance. Two active, prospective, population-based surveillance systems were established for monitoring influenza and other respiratory pathogens among those hospitalized patients with acute respiratory illness and those enrolled patients seeking consultations at sentinel general practices. In 2015, a sero-epidemiological study will use a sample of patients from the same practices. These data will provide a full picture of the disease burden and risk factors from asymptomatic infections to severe hospitalized disease and deaths and related economic burden. The results during the first 2 years (2012-2013) provided scientific evidence to (a) support a change to NZ's vaccination policy for young children due to high influenza hospitalizations in these children; (b) contribute to the revision of the World Health Organization's case definition for severe acute respiratory illness for global influenza surveillance; and (c) contribute in part to vaccine strain selection using vaccine effectiveness assessment in the prevention of influenza-related consultations and hospitalizations. In summary, SHIVERS provides valuable international platforms for supporting seasonal influenza control and pandemic preparedness, and responding to other emerging/endemic respiratory-related infections.
Pellegrino, Paolo; Carnovale, Carla; Perrone, Valentina; Pozzi, Marco; Antoniazzi, Stefania; Radice, Sonia; Clementi, Emilio
Multiple sclerosis is a chronic progressive demyelinating disease affecting over 2.1 million patients worldwide. Patients affected by MS are exposed to an increased risk of infection from communicable diseases, which may lead to severe disease relapses. Studies have analysed the issue of vaccination of MS-affected patients. These studies, however, deal mostly with safety-related issues documenting that most vaccines have been proven to be safe in MS patients and that vaccination is not associated with an increased risk of relapses. By contrast, evidence on the efficacy is comparatively scant and not yet systematised in a comprehensive picture. This aspect is however important, as both MS and its treatment alter the immune responses, a situation that may be associated with a reduced vaccine efficacy. We have now reviewed the literature and assessed the effects of the therapy for MS on vaccine efficacy; we focused on the vaccine against influenza as for the other vaccines the information is still too scant. The majority of drugs appear not associated with a reduced response to vaccination against influenza, with the notable exception of mitoxantrone and glatiramer acetate. For a few drugs, among which natalizumab, information is not sufficiently clear and additional studies are needed to draw a definite conclusion. These results highlight the importance to evaluate the efficacy of vaccination in patients treated with immunosuppressant drugs.
Gross, P A; Weksler, M E; Quinnan, G V; Douglas, R G; Gaerlan, P F; Denning, C R
A total of 104 elderly patients were immunized with one or two doses of the commercial 1985-1986 inactivated influenza vaccine formulation. Two types of vaccines (split virus [SV] vaccine and whole virus [WV] vaccine) and one or two doses 1 month apart were given. No difference in local or systemic reactions was noted among the four groups. The reciprocal geometric mean hemagglutination inhibition antibody titers against influenza A/Philippines/82 (H3N2) after one or two doses were: 78 for SV vaccine (one dose), 65 for SV vaccine (two doses), 55 for WV vaccine (one dose), and 51 for WV vaccine (two doses). Similar nonsignificant differences were observed for the other two antigens contained in the vaccine. The percentage with a hemagglutination inhibition titer of greater than or equal to 1:40 also did not differ after one or two doses. We then compared the postvaccination hemagglutination inhibition titers in young and old patients from previous studies in which apparent differences had appeared. We retested all sera simultaneously on the same day with the same reagents. No significant differences were apparent among age groups. In summary, the humoral immune response to inactivated influenza vaccine in healthy ambulatory elderly patients who have been previously immunized may not differ significantly from that of children and young adults. A booster dose 1 month after the first dose does not enhance immune responses in the elderly.
Wen, Yingxia; Han, Liqun; Palladino, Giuseppe; Ferrari, Annette; Xie, Yuhong; Carfi, Andrea; Dormitzer, Philip R; Settembre, Ethan C
Influenza vaccines are the primary intervention for reducing the substantial health burden from pandemic and seasonal influenza. Hemagglutinin (HA) is the most important influenza vaccine antigen. Subunit and split influenza vaccines are formulated, released for clinical use, and tested for stability based on an in vitro potency assay, single-radial immunodiffusion (SRID), which selectively detects HA that is immunologically active (capable of eliciting neutralizing or hemagglutination inhibiting antibodies in an immunized subject). The time consuming generation of strain-specific sheep antisera and calibrated antigen standards for SRID can delay vaccine release. The limitation in generating SRID reagents was evident during the early days of the 2009 pandemic, prompting efforts to develop more practical, alternative, quantitative assays for immunologically active HA. Here we demonstrate that, under native conditions, trypsin selectively digests HA produced from egg or mammalian cell in monovalent vaccines that is altered by stress conditions such as reduced pH, elevated temperature, or deamidation, leaving native, pre-fusion HA, intact. Subsequent reverse-phase high pressure liquid chromatography (RP-HPLC) can separate trypsin-resistant HA from the digested HA. Integration of the resulting RP-HPLC peak yields HA quantities that match well the values obtained by SRID. Therefore, trypsin digestion, to pre-select immunologically active HA, followed by quantification by RP-HPLC is a promising alternative in vitro potency assay for influenza vaccines.
Leiderman, Eduardo; Mogabgab, William J.
An experimental vaccine prepared from influenza virus strains propagated in bovine kidney cell cultures, purified by zonal centrifugation, and further treated with ether was studied in man for the incidence of clinical reactions and hemagglutination-inhibition antibody levels induced. The results were equivalent to those obtained in a simultaneous study made with a commercially licensed influenza vaccine derived from viruses propagated in the embryonated egg and also purified by zonal centrifugation, but not treated with ether. Comparison of the macromethod and the micromethod for determination of hemagglutination-inhibition antibody titers revealed that lower initial titers and lesser increments in antibody levels following vaccination were obtained by the microtechnique. PMID:4905036
Virk, Ramandeep Kaur; Gunalan, Vithiagaran; Tambyah, Paul Anantharajah
Influenza is a ubiquitous infection with a spectrum ranging from mild to severe. The mystery regarding such variability in the clinical spectrum has not been fully unravelled, although a role for the complex interplay among virus characteristics, host immune response and environmental factors has been suggested. Antivirals and current vaccines have a limited role in prophylaxis and treatment because they primarily target surface glycoproteins which undergo antigenic/genetic changes under host immune pressure. Targeting conserved internal proteins could lead the way to a universal vaccine which can be used against various types/subtypes. However, this is on the distant horizon, so in the meantime, developing improved vaccines should be given high priority. In this review, we discuss where the current influenza research stands in terms of vaccines, adjuvants, and how we can better predict the vaccine strains for upcoming influenza seasons by understanding complex phenomena which drive the continuous antigenic evolution.
Moreno-Pérez, D; Arístegui Fernández, J; Ruiz-Contreras, J; Alvarez García, F J; Merino Moína, M; González-Hachero, J; Corretger Rauet, J M; Hernández-Sampelayo Matos, T; Ortigosa del Castillo, L; Cilleruelo Ortega, M J; Barrio Corrales, F
The Advisory Committee on Vaccines of the Spanish Association of Paediatrics establishes annual recommendations on influenza vaccination in childhood before the onset of influenza season. Routine influenza vaccination is particularly beneficial when the strategy is aimed at children older than 6 months of age with high-risk conditions and their home contacts. The recommendation of influenza vaccination in health workers with children is also emphasized.
Shahrabani, Shosh; Benzion, Uri
The study examined the factors affecting the decision to be vaccinated against influenza among employees in Israel. The research, conducted in 2007/2008, included 616 employees aged 18−65 at various workplaces in Israel, among them companies that offered their employees influenza vaccination. The research questionnaire included socio-demographic characteristics, and the Health Belief Model principles. The results show that the significant factors affecting vaccination compliance include a vaccination program at workplaces, vaccinations in the past, higher levels of vaccine’s perceived benefits, and lower levels of barriers to getting the vaccine. We conclude that vaccine compliance is larger at companies with workplace vaccination programs providing easier accessibility to vaccination. PMID:20617008
Song, Langzhou; Liu, Ge; Umlauf, Scott; Liu, Xiangyu; Li, Hong; Tian, Haijun; Reiserova, Lucia; Hou, Fuxiang; Bell, Rodney; Tussey, Lynda
Previously, we demonstrated that for H1N1 and H5N1 influenza strains, the globular head of the hemagglutinin (HA) antigen fused to flagellin of Salmonella typhimurium fljB (STF2) is highly immunogenic in preclinical models and man (Song et al. (2008) ; Song et al. (2009) ; Taylor et al. (2012) ). Further we showed that the vaccine format, or point of attachment of the vaccine antigen to flagellin, can dramatically affect the immunogenicity and safety profile of the vaccine. However, Influenza B vaccines based on these formats are poor triggers of TLR5 and consequently are poorly immunogenic. Through rational design, here we show that we have identified a fusion position within domain 3 of flagellin that improves TLR5 signaling and consequently, immunogenicity of multiple influenza B vaccines. Our results demonstrate that, similar to influenza A strains, the protective subunit of the influenza B HA can be fused to flagellin and produced in a standard prokaryotic expression system thereby allowing for cost and time efficient production of multivalent seasonal influenza vaccines.
Safety of the 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines.
Prymula, Roman; Chlibek, Roman; Splino, Miroslav; Kaliskova, Eva; Kohl, Igor; Lommel, Patricia; Schuerman, Lode
This randomized (1:1), double-blind, multicenter study, included 4,968 healthy infants to receive either the 11-valent pneumococcal protein D (PD)-conjugate study vaccine or the hepatitis A vaccine (HAV) (control) at 3, 4, 5, and 12-15 months of age. The three-dose primary course of both vaccines was co-administered with combined hexavalent DTPa-HBV-IPV/Hib vaccine. The pneumococcal PD-conjugate study vaccine did not impact the immune response of co-administered hexavalent vaccine and the control HAV vaccine induced seropositivity (antibodies >or=15 mIU/mL) in all infants. The incidence of solicited symptoms was higher with the 11-valent pneumococcal PD-conjugate study vaccine, yet similar to that induced by concomitant DTPa-HBV-IPV/Hib vaccine. Overall, the reactogenicity and safety profile of the 11-valent pneumococcal PD-conjugate vaccine when co-administered with the hexavalent DTPa-HBV-IPV/Hib vaccine, as well as the immunogenicity of the co-administered hexavalent vaccine, were consistent with previous reports for the licensed DTPa-HBV-IPV/Hib and pneumococcal conjugate vaccines.
... Influenza Vaccination Week, 2010 8472 Proclamation 8472 Presidential Documents Proclamations Proclamation 8472 of January 8, 2010 Proc. 8472 National Influenza Vaccination Week, 2010By the President of the... complications, resulting in hospitalization or even death. We know that influenza vaccination is the best way...
Safety, reactogenicity and immunogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children in the second year of life: Results from an open study.
Dicko, Alassane; Dicko, Yahia; Barry, Amadou; Sidibe, Youssoufa; Mahamar, Almahamoudou; Santara, Gaoussou; Dolo, Amagana; Diallo, Aminata; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Strezova, Ana; Borys, Dorota; Schuerman, Lode
Pneumonia is still the leading cause of death among African children with pneumococcal serotypes 1 and 5 being dominant in the below 5 y of age group. The present study assessed the safety, reactogenicity and immunogenicity of a 2-dose catch-up vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) in Malian children. This phase III, open-label study (NCT00985465) was conducted in Ouelessebougou, Mali, between November 2009 and July 2010. The study population consisted of PHiD-CV unprimed Malian children previously enrolled in the control group of study NCT00678301 receiving a 2-dose catch-up vaccination with PHiD-CV in the second year of life. Adverse events were recorded following each PHiD-CV dose. Antibody responses and opsonophagocytic activity (OPA) were measured pre-vaccination and after the second PHiD-CV catch-up dose. Swelling and fever (axillary temperature ≥ 37.5°C) were the most frequently reported solicited symptoms following either PHiD-CV dose. Few grade 3 solicited symptoms were reported. Large swelling reactions and serious adverse events were not reported. Post-catch-up vaccination, for each vaccine pneumococcal serotype, at least 94.7% of subjects had antibody concentrations ≥ 0.2 μg/ml, except for serotypes 6B (82.5%) and 23F (87.7%). At least 94.0% of subjects had OPA titres ≥ 8, except for serotype 19F (89.4%). The geometric mean concentration for antibodies against protein D was 839.3 (95% CI: 643.5-1094.6) EL.U/ml. Two-dose PHiD-CV catch-up regimen in the second year of life was well-tolerated and immunogenic for all vaccine pneumococcal serotypes and NTHi protein D when administered to Malian children.
Safety, reactogenicity and immunogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children in the second year of life: Results from an open study
Dicko, Alassane; Dicko, Yahia; Barry, Amadou; Sidibe, Youssoufa; Mahamar, Almahamoudou; Santara, Gaoussou; Dolo, Amagana; Diallo, Aminata; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Strezova, Ana; Borys, Dorota; Schuerman, Lode
Pneumonia is still the leading cause of death among African children with pneumococcal serotypes 1 and 5 being dominant in the below 5 y of age group. The present study assessed the safety, reactogenicity and immunogenicity of a 2-dose catch-up vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) in Malian children. This phase III, open-label study (NCT00985465) was conducted in Ouelessebougou, Mali, between November 2009 and July 2010. The study population consisted of PHiD-CV unprimed Malian children previously enrolled in the control group of study NCT00678301 receiving a 2-dose catch-up vaccination with PHiD-CV in the second year of life. Adverse events were recorded following each PHiD-CV dose. Antibody responses and opsonophagocytic activity (OPA) were measured pre-vaccination and after the second PHiD-CV catch-up dose. Swelling and fever (axillary temperature ≥ 37.5°C) were the most frequently reported solicited symptoms following either PHiD-CV dose. Few grade 3 solicited symptoms were reported. Large swelling reactions and serious adverse events were not reported. Post-catch-up vaccination, for each vaccine pneumococcal serotype, at least 94.7% of subjects had antibody concentrations ≥ 0.2 μg/ml, except for serotypes 6B (82.5%) and 23F (87.7%). At least 94.0% of subjects had OPA titres ≥ 8, except for serotype 19F (89.4%). The geometric mean concentration for antibodies against protein D was 839.3 (95% CI: 643.5-1094.6) EL.U/ml. Two-dose PHiD-CV catch-up regimen in the second year of life was well-tolerated and immunogenic for all vaccine pneumococcal serotypes and NTHi protein D when administered to Malian children PMID:26020101
Goel, M K; Goel, M; Khanna, P; Mittal, K
The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 countries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO) announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009) virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.
Black, Steven; Nicolay, Uwe; Del Giudice, Giuseppe; Rappuoli, Rino
Influenza vaccination strategies have targeted elderly individuals because they are at high risk of disease complications and mortality. Statins are a class of drugs used to treat hypercholesterolemia and are frequently used in the elderly population to reduce the risk of cardiovascular disease. However, statins are also known to have immunomodulatory effects that could impact influenza vaccine response. In a post hoc analysis, we performed a cross-sectional observational study nested within a comparative immunogenicity clinical trial of adjuvanted versus unadjuvanted influenza vaccine in elderly persons to evaluate the influence of statin therapy on the immune response to vaccination. Overall, data on >5000 trial participants were available for analysis. Comparison of hemagglutination-inhibiting geometric mean titers to influenza A(H1N1), A(H3N2), and B strains revealed that titers were 38% (95% confidence interval [CI], 27%-50%), 67% (95% CI, 54%-80%), and 38% (95% CI, 28%-29%) lower, respectively, in subjects receiving chronic statin therapy, compared with those not receiving chronic statin therapy. This apparent immunosuppressive effect of statins on the vaccine immune response was most dramatic in individuals receiving synthetic statins. These effects were seen in both the adjuvanted and unadjuvanted vaccine groups in the clinical trial. These results, if confirmed, could have implications both for future clinical trials design, as well as for vaccine use recommendations for elderly individuals.
de PAULA, Stéfano Ivani; de PAULA, Gustavo Ivani; CUNEGUNDES, Kelly Simone Almeida; de MORAES-PINTO, Maria Isabel
SUMMARY This study evaluated the adherence to influenza vaccination among medical students in 2010 and 2011. From August to December 2011, a questionnaire was used to record the influenza vaccination in 2010 and 2011, reasons for acceptance of the influenza vaccine and knowledge of healthcare workers about the influenza vaccine recommendation. One hundred and forty-four students from the 2ndto the 6th years of the medical school were interviewed. A great adherence to pandemic influenza vaccine was noted in 2010, (91% of the students), with "self-protection" being the most common reason cited for vaccination. Other determinants for the vaccination during pandemic were "convenient access to vaccine" and "encouragement by peers and teachers in workplaces and at the university". However, there was a great decay in the acceptance to vaccine in the next influenza season (2011). Only 42% of the students received the vaccine. They claimed "lack of time" and "have forgotten to take the vaccine" as the main reasons. The "knowledge on the recommendation of influenza vaccine to healthcare workers" increased when the students come to attend the last year of the medical school, but that was an insufficient motivator for vaccination. Strategies to increase vaccination should be based on the abovementioned aspects for the adoption of effective measures in both, pandemic and seasonal periods. PMID:27828623
Paula, Stéfano Ivani de; Paula, Gustavo Ivani de; Cunegundes, Kelly Simone Almeida; Moraes-Pinto, Maria Isabel de
This study evaluated the adherence to influenza vaccination among medical students in 2010 and 2011. From August to December 2011, a questionnaire was used to record the influenza vaccination in 2010 and 2011, reasons for acceptance of the influenza vaccine and knowledge of healthcare workers about the influenza vaccine recommendation. One hundred and forty-four students from the 2ndto the 6th years of the medical school were interviewed. A great adherence to pandemic influenza vaccine was noted in 2010, (91% of the students), with "self-protection" being the most common reason cited for vaccination. Other determinants for the vaccination during pandemic were "convenient access to vaccine" and "encouragement by peers and teachers in workplaces and at the university". However, there was a great decay in the acceptance to vaccine in the next influenza season (2011). Only 42% of the students received the vaccine. They claimed "lack of time" and "have forgotten to take the vaccine" as the main reasons. The "knowledge on the recommendation of influenza vaccine to healthcare workers" increased when the students come to attend the last year of the medical school, but that was an insufficient motivator for vaccination. Strategies to increase vaccination should be based on the abovementioned aspects for the adoption of effective measures in both, pandemic and seasonal periods.
Zholobak, Nadezhda M; Mironenko, Alla P; Shcherbakov, Alexander B; Shydlovska, Olga A; Spivak, Mykola Ya; Radchenko, Larysa V; Marinin, Andrey I; Ivanova, Olga S; Baranchikov, Alexander E; Ivanov, Vladimir K
We have demonstrated the influence of cerium dioxide nanoparticles on the immunogenicity of the influenza vaccine on an example of liquid split inactivated Vaxigrip vaccine. Antibody titers were analyzed using the hemagglutination inhibition (HI) assay. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. The effect of nano-ceria surface stabilizer on the enhancement of immunogenicity was shown. The vaccine modified by citrate-stabilized nano-ceria, in contrast to a non-modified Vaxigrip vaccine, did not provide an adequate level of seroprotection, and seroconversion after vaccination was 66.7% on days 49-63 for virus strain А(H1N1) and 100% on day 49 for virus strain B/Yamagata. For the low immunogenic influenza B virus, the rise in antibody titers (GMT/IF) was 24.38/3.28 after the first injection and 50.40/6.79 on day 49. For the vaccine modified by non-stabilized nano-ceria, for all virus strains under study, on day 63, upon immunization notable levels of seroprotection, seroconversion and GMT/IF were registered (higher than for the non-modified Vaxigrip vaccine). The successful attempt to modify the influenza vaccine demonstrates the possible ways of increasing the specific activity of vaccines using nano-ceria.
Rocchi, G.; Ragona, G.; Piga, C.; Pelosio, A.; Volpi, A.; Vella, S.; Legniti, N.; de Felici, A.
Immunization procedures with live attenuated and inactivated vaccines were carried out on a group of young recruits at the beginning of an outbreak of infection due to an A/Victoria/3/75-related virus strain, which occurred in February 1977 in a military camp. A retrospective investigation on protection from clinical influenza was then performed in order to investigate whether immunization with live virus vaccines, administered at the beginning of an epidemic, could provide early protection from the disease. In the course of the two weeks following vaccination, laboratory-confirmed clinical influenza cases occurred in 4 subjects among the 110 volunteers of the control group which received placebo, and in 8, 7 and 4 subjects respectively of the 3 groups of about 125 individuals, each of which received one of the following vaccine preparations: (a), live attenuated A/Victoria/3/75 influenza virus oral vaccine, grown on chick embryo kidney culture; (b), live attenuated nasal vaccine, a recombinant of A/Puerto Rico/8/34 with A/Victoria/3/75 virus; and (c), inactivated A/Victoria/3/75 virus intramuscular vaccine. These data do not support the hypothesis that, during an epidemic of infection, early protection from clinical influenza can be achieved through immunization with live attenuated or inactivated influenza virus vaccines, in spite of the high immunizing capability of the vaccine preparations. PMID:512351
Kashirina, O S; Vasil'ev, Iu M
Comparative evaluation of live attenuated and inactivated influenza vaccines based on data from direct comparative studies is necessary for ensuring the most effective and safe vaccination against influenza. Analysis of direct comparative preclinical and clinical studies of inactivated and live cold-adapted (ca) influenza vaccines showed that published data are inconsistent and limited for some population groups. Live ca vaccines may be promising as an alternative or addition to inactivated vaccines especially for mass vaccination against influenza in children as well as in the elderly when combined with inactivated vaccines. Further studies of inactivated and live ca influenza vaccines in direct comparative studies that control the administration route and vaccine strain production as well as development and confirmation of objective criteria of live attenuated influenza vaccine effectiveness evaluation are necessary.
Castilla, Jesús; Guevara, Marcela; Martínez-Baz, Iván; Ezpeleta, Carmen; Delfrade, Josu; Irisarri, Fátima; Moreno-Iribas, Conchi
Abstract Mortality is a major end-point in the evaluation of influenza vaccine effectiveness. However, this effect is not well known, since most previous studies failed to show good control of biases. We aimed to estimate the effectiveness of influenza vaccination in preventing all-cause mortality in community-dwelling seniors. Since 2009, a population-based cohort study using healthcare databases has been conducted in Navarra, Spain. In 2 late influenza seasons, 2011/2012 and 2012/2013, all-cause mortality in the period January to May was compared between seniors (65 years or over) who received the trivalent influenza vaccine and those who were unvaccinated, adjusting for demographics, major chronic conditions, dependence, previous hospitalization, and pneumococcal vaccination. The cohort included 103,156 seniors in the 2011/2012 season and 105,140 in the 2012/2013 season (58% vaccinated). Seniors vaccinated in the previous season who discontinued vaccination (6% of the total) had excess mortality and were excluded to prevent frailty bias. The final analysis included 80,730 person-years and 2778 deaths. Vaccinated seniors had 16% less all-cause mortality than those unvaccinated (adjusted rate ratio [RR] = 0.84; 95% confidence interval 0.76–0.93). This association disappeared in the post-influenza period (adjusted RR = 0.96; 95% confidence interval 0.85–1.09). A similar comparison did not find an association in January to May of the 2009/2010 pandemic season (adjusted RR = 0.98; 95% confidence interval 0.84–1.14), when no effect of the seasonal vaccine was expected. On average, 1 death was prevented for every 328 seniors vaccinated: 1 for every 649 in the 65 to 74 year age group and 1 for every 251 among those aged 75 and over. These results suggest a moderate preventive effect and a high potential impact of the seasonal influenza vaccine against all-cause mortality. This reinforces the recommendation of annual influenza vaccination in seniors
Hadler, James L
In order to consider the ethical issues around vaccine distribution during an influenza pandemic, it is critical to have an understanding of the role of influenza vaccine in a pandemic, the rate at which vaccine is likely to be come available, who will likely produce and "own" the vaccine, how vaccine distribution and administration might be accomplished, and which are the groups that might be deemed highest priority to be vaccinated against influenza. The United States and Connecticut have been considering the more challenging of these issues and have learned from Canada, which previously discussed and made decisions on the challenges related to vaccine distribution. Although there is still some critical advance thinking that needs to be done, planning for the response to an influenza pandemic is now at an advanced stage. The keys to preparedness at this stage are to be aware of the vaccine distribution options, to know the benefits and limitations of each option, and to be flexible but nimble in dealing with a real pandemic.
Milián, Ernest; Kamen, Amine A.
Annually, influenza virus infects millions of people worldwide. Vaccination programs against seasonal influenza infections require the production of hundreds of million doses within a very short period of time. The influenza vaccine is currently produced using a technology developed in the 1940s that relies on replicating the virus in embryonated hens' eggs. The monovalent viral preparation is inactivated and purified before being formulated in trivalent or tetravalent influenza vaccines. The production process has depended on a continuous supply of eggs. In the case of pandemic outbreaks, this mode of production might be problematic because of a possible drastic reduction in the egg supply and the low flexibility of the manufacturing process resulting in a lack of supply of the required vaccine doses in a timely fashion. Novel production systems using mammalian or insect cell cultures have emerged to overcome the limitations of the egg-based production system. These industrially well-established production systems have been primarily selected for a faster and more flexible response to pandemic threats. Here, we review the most important cell culture manufacturing processes that have been developed in recent years for mass production of influenza vaccines. PMID:25815321
Jang, Yo Han; Seong, Baik Lin
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.
Report on the first WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Hong Kong SAR, China, 24-26 January 2013.
Girard, Marc P; Tam, John S; Pervikov, Yuri; Katz, Jacqueline M
On January 24-26, 2013, the World Health Organization convened the first integrated meeting on "The development and clinical trials of vaccines that induce broadly protective and long-lasting immune responses" to review the current status of development and clinical evaluation of novel influenza vaccines as well as strategies to produce and deliver vaccines in novel ways. Special attention was given to the development of possible universal influenza vaccines. Other topics that were addressed included an update on clinical trials of pandemic and seasonal influenza vaccines in high-risk groups and vaccine safety, as well as regulatory issues.
Lee, Vernon J.; Tok, Mei Yin; Chow, Vincent T.; Phua, Kai Hong; Ooi, Eng Eong; Tambyah, Paul A.; Chen, Mark I.
Background All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. Methodology We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. Principal Findings The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4–0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. Conclusions The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines. PMID:19771173
Background Influenza vaccination is the most efficient and cost-effective method to prevent influenza. To increase vaccination coverage, health authorities use various intervention programs (IPs), such as cost subsidies or placing vaccination centers in malls to make vaccination more accessible. Nevertheless, vaccination coverage has been sub-optimal in most developed countries, including in Israel. Methods To determine possible drivers of individual vaccination uptake and to examine the effectiveness of different IPs in increasing vaccination, we analyzed a telephone survey of a representative sample of the Israeli population conducted in March 2011 (n = 470), and paper questionnaires at the work place and at homes during April-July 2011 to several sub-populations : soldiers (n = 81), medical staff (n = 107), ultra-orthodox Jews (n = 72), Israeli Arabs (n = 87) and students (n = 85). Results The population can be stratified into three sub-groups: Acceptors, who receive vaccination regardless of IPs (22%), Conditional Acceptors, who are only vaccinated because of IP implementation (44%) and Non-Acceptors, who are not vaccinated despite IP implementation (34%). Our analysis shows that the risk perception towards influenza relative to vaccination is higher in the Acceptors than in the Conditional Acceptors, with the Non-Acceptors showing the lowest risk perception (P < 0.01). For Conditional Acceptors, physician recommendation is the most effective IP, regardless of the sub-population tested (P = 0.04). Students and low-income participants were more prone than any others to be persuaded to receive vaccination following IPs. In addition, financial incentives were more effective for ultra-religious orthodox Jews and students; vaccinations in more accessible areas were more effective for the ultra-religious orthodox, soldiers, and medical personnel; and TV and radio advertisements were more effective for people above 50 relative to other
Flannery, Brendan; Chung, Jessie R; Thaker, Swathi N; Monto, Arnold S; Martin, Emily T; Belongia, Edward A; McLean, Huong Q; Gaglani, Manjusha; Murthy, Kempapura; Zimmerman, Richard K; Nowalk, Mary Patricia; Jackson, Michael L; Jackson, Lisa A; Foust, Angie; Sessions, Wendy; Berman, LaShondra; Spencer, Sarah; Fry, Alicia M
In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). Each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent influenza-associated, medically attended, acute respiratory illness (ARI). This report uses data, as of February 4, 2017, from 3,144 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 28, 2016-February 4, 2017, to estimate an interim adjusted effectiveness of seasonal influenza vaccine for preventing laboratory-confirmed influenza virus infection associated with medically attended ARI. During this period, overall vaccine effectiveness (VE) (adjusted for study site, age group, sex, race/ethnicity, self-rated general health, and days from illness onset to enrollment) against influenza A and influenza B virus infection associated with medically attended ARI was 48% (95% confidence interval [CI] = 37%-57%). Most influenza infections were caused by A (H3N2) viruses. VE was estimated to be 43% (CI = 29%-54%) against illness caused by influenza A (H3N2) virus and 73% (CI = 54%-84%) against influenza B virus. These interim VE estimates indicate that influenza vaccination reduced the risk for outpatient medical visits by almost half. Because influenza activity remains elevated (2), CDC and the Advisory Committee on Immunization Practices recommend that annual influenza vaccination efforts continue as long as influenza viruses are circulating (1). Vaccination with 2016-17 influenza vaccines will reduce the number of infections with most currently circulating influenza viruses. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated as soon as possible.
"Immunization Safety" (i.e., ensuring and monitoring the safety of all aspects of immunization, including vaccine quality, storage and handling, vaccine administration and the disposal of sharps) remains a major challenge. Any vaccine safety issue, real or perceived, may lead to rumors and undermine confidence in vaccination and, ultimately, have dramatic consequences for immunization coverage and disease incidence. In 1999, WHO's Department of Vaccines and Biologicals launched the Immunization Safety Priority Project to establish a comprehensive system to ensure the safety of all immunizations given in national immunization programmes. The project aims at strengthening each country's capacity. The principal areas of activity of the project include: research and development of safer vaccines and safer and simpler vaccine delivery technologies; assurance of vaccine safety through quality control procedures and quality specifications; implementation of tools to ensure vaccine quality up to vaccine administration; access to safe and efficient vaccine administration technologies and their disposal; and identification and management of risks related to immunization. This report focuses on the latter area and highlights challenges and critical factors in establishing a safety profile for a vaccine and the importance and limits of post market surveillance. It presents some of WHO's supporting activities among which the establishment of a Global Advisory Committee on Vaccine Safety to provide an independent scientific assessment of vaccine safety issues. WHO has a role to play not only because of its technical and normative role but also because of its privileged relation with country authorities and its global vision and mandate and being perceived as neutral and free of conflicts of interest.
Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A.; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L.; Van Hoeven, Neal; Vedvick, Thomas S.; Huynh, Chuong; O'Hara, Michael K.; Noah, Diana L.; Fox, Christopher B.
abstract Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness. PMID:26618392
Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.
Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B
Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.
Huang, Kuan-Ying A.; Chang, Shih-Cheng; Huang, Yhu-Chering; Chiu, Cheng-Hsun; Lin, Tzou-Yien
Inactivated influenza vaccination induces a hemagglutinin-specific antibody response to the strain used for immunization. Annual vaccination is strongly recommended for health care personnel. However, it is debatable if repeated vaccination would affect the antibody response to inactivated influenza vaccine through the time. We enrolled health care personnel who had repeated and first trivalent inactivated influenza vaccination in 2005–2008. Serological antibody responses were measured by hemagglutination-inhibition (HI) test. Subjects with repeated vaccination had higher pre-vaccination and lower post-vaccination HI titer than those with first vaccination, although serological responses between groups might vary with different antigen types and while the drifted strain was introduced in the vaccine. Higher fold rise in the HI titer was observed in the group with first than repeated vaccination and the fold increase in the HI titer was inversely correlated with pre-vaccination titer in 2007 and 2008. Nevertheless, no significant difference in the day 28 seroprotection rate was observed between groups with repeated and first vaccination in most circumstances. Further studies are needed to understand the long-term effect of repeated vaccination on the antibody response both at the serological and repertoire levels among health care personnel. PMID:28098157
Mossad, Sherif B
FluMist--a cold-adapted, live-attenuated, trivalent, intranasal influenza virus vaccine approved by the US Food and Drug Administration on June 17, 2003--has been shown to be safe and effective, but its role in the general prevention of influenza is yet to be defined. Intranasal administration is expected to be more acceptable than parenteral, particularly in children, but the potential for the shedding of live virus may pose a risk to anyone with a compromised immune system.
Shoji, Yoko; Chichester, Jessica A; Jones, Mark; Manceva, Slobodanka D; Damon, Emily; Mett, Vadim; Musiychuk, Konstantin; Bi, Hong; Farrance, Christine; Shamloul, Moneim; Kushnir, Natasha; Sharma, Satish; Yusibov, Vidadi
In 2009, a novel H1N1 swine influenza virus was isolated from infected humans in Mexico and the United States, and rapidly spread around the world. Another virus, a highly pathogenic avian influenza virus of the H5N1 subtype, identified by the World Health Organization as a potential pandemic threat in 1997, continues to be a significant risk. While vaccination is the preferred strategy for the prevention and control of influenza infections, the traditional egg-based approach to producing influenza vaccines does not provide sufficient capacity and adequate speed to satisfy global needs to combat newly emerging strains, seasonal or potentially pandemic. Significant efforts are underway to develop and implement new cell substrates with improved efficiency for influenza vaccine development and manufacturing. In recent years, plants have been used to produce recombinant proteins including subunit vaccines and antibodies. The main advantages of using plant systems for the production of vaccine antigens against influenza are their independence from pathogenic viruses, and cost and time efficiency. Here, we describe the large-scale production of recombinant hemagglutinin proteins from A/California/04/09 (H1N1) and A/Indonesia/05/05 (H5N1) strains of influenza virus in Nicotiana benthamiana plants, and their immunogenicity (serum hemagglutination inhibition and virus neutralizing antibodies), and safety in animal models. These results support the testing of these candidate vaccines in human volunteers and also the utility of our plant expression system for large-scale recombinant influenza vaccine production.
François, Guido; Duclos, Philippe; Margolis, Harold; Lavanchy, Daniel; Siegrist, Claire-Anne; Meheus, André; Lambert, Paul-Henri; Emiroğlu, Nedret; Badur, Selim; Van Damme, Pierre
In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine "scares" continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.
Spackman, Erica; Pantin-Jackwood, Mary J
Although little has changed in vaccine technology for avian influenza virus (AIV) in the past 20 years, the approach to vaccination of poultry (chickens, turkeys and ducks) for avian influenza has evolved as highly pathogenic AIV has become endemic in several regions of the world. Vaccination for low pathogenicity AIV is also becoming routine in regions where there is a high level of field challenge. In contrast, some countries will not use vaccination at all and some will only use it on an emergency basis during eradication efforts (i.e. stamping-out). There are pros and cons to each approach and, since every outbreak situation is different, no one method will work equally well in all situations. Numerous practical aspects must be considered when developing an AIV control program with vaccination as a component, such as: (1) the goals of vaccination must be defined; (2) the population to be vaccinated must be clearly identified; (3) there must be a plan to obtain and administer good quality vaccine in a timely manner and to achieve adequate coverage with the available resources; (4) risk factors for vaccine failure should be mitigated as much as possible; and, most importantly, (5) biosecurity must be maintained as much as possible, if not enhanced, during the vaccination period.
Scheminske, Megan; Henninger, Michelle; Irving, Stephanie A.; Thompson, Mark; Williams, Jenny; Shifflett, Pat; Ball, Sarah W.; Avalos, Lyndsay Ammon; Naleway, Allison L.
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…
de Castro, Breno Augusto Campos; Pereira, Juliana Milagres Macedo; Meyer, Renata Leal Bregunci; Trindade, Fernanda Marques; Pedrosa, Moises Salgado; Piancastelli, André Costa Cruz
The etiology of pityriasis lichenoides is unknown. One of the accepted theories admits that PL is an inflammatory response to extrinsic antigens such as infectious agents, drugs and vaccines. In recent medical literature, only the MMR vaccine (Measles, Mumps and Rubella) was associated with the occurrence of this disease. We present a case of a male, 12 year old healthy patient who, five days after Infl uenza vaccination, developed erythematous papules on the trunk, abdomen and limbs, some with adherent crusts and associated systemic symptoms. This case report is notable for describing the first case of pityriasis lichenoides et varioliformis acuta associated with the vaccine against Influenza. PMID:26312710
Curran, T; McCaughey, C; Ellis, J; Mitchell, S J; Feeney, S A; Watt, A P; Mitchell, F; Fairley, D; Crawford, L; McKenna, J; Coyle, P V
False-positive PCR results usually occur as a consequence of specimen-to-specimen or amplicon-to-specimen contamination within the laboratory. Evidence of contamination at time of specimen collection linked to influenza vaccine administration in the same location as influenza sampling is described. Clinical, circumstantial and laboratory evidence was gathered for each of five cases of influenza-like illness (ILI) with unusual patterns of PCR reactivity for seasonal H1N1, H3N2, H1N1 (2009) and influenza B viruses. Two 2010 trivalent influenza vaccines and environmental swabs of a hospital influenza vaccination room were also tested for influenza RNA. Sequencing of influenza A matrix (M) gene amplicons from the five cases and vaccines was undertaken. Four 2009 general practitioner (GP) specimens were seasonal H1N1, H3N2 and influenza B PCR positive. One 2010 GP specimen was H1N1 (2009), H3N2 and influenza B positive. PCR of 2010 trivalent vaccines showed high loads of detectable influenza A and B RNA. Sequencing of the five specimens and vaccines showed greatest homology with the M gene sequence of Influenza A/Puerto Rico/8/1934 H1N1 virus (used in generation of influenza vaccine strains). Environmental swabs had detectable influenza A and B RNA. RNA detection studies demonstrated vaccine RNA still detectable for at least 66 days. Administration of influenza vaccines and clinical sampling in the same room resulted in the contamination with vaccine strains of surveillance swabs collected from patients with ILI. Vaccine contamination should therefore be considered, particularly where multiple influenza virus RNA PCR positive signals (e.g. H1N1, H3N2 and influenza B) are detected in the same specimen.
Lambach, Philipp; Alvarez, Alba Maria Ropero; Hirve, Siddhivinayak; Ortiz, Justin R; Hombach, Joachim; Verweij, Marcel; Hendriks, Jan; Palkonyay, Laszlo; Pfleiderer, Michael
There is potential for influenza vaccine programmes to make a substantial impact on severe disease in low-resource settings, however questions around vaccine composition and programmatic issues will require special attention. Some countries may benefit from immunization programmes that provide year-round supply of vaccine; however the best way to ensure adequate vaccine supply has yet to be determined. In this report, we discuss vaccine composition, availability, and programmatic issues that must be considered when developing year-round influenza immunization programmes. We then explore how these considerations have influenced immunization practices in the Latin American region as a case study. We identify three different approaches to achieve year-round supply: (1) alternating between Northern Hemisphere and Southern Hemisphere formulations, (2) extending the expiration date to permit extended use of a single hemisphere formulation, and (3) local vaccine manufacture with production timelines that align with local epidemiology. Each approach has its challenges and opportunities. The growing data suggesting high influenza disease burden in low resource countries underscores the compelling public health need to determine the best strategies for vaccine delivery.
Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M. Carolina; Ruiz-Matus, Cuauhtémoc
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
GAMOH, Koichiro; NAKAMURA, Shigeyuki
Japan established a vaccine selection system, in which a committee evaluates veterinary influenza vaccines to determine if the vaccine should be updated. In 2013, it was concluded that the present equine influenza vaccine strains did not have to be updated, but clade 2 (Fc2) viruses of the Florida sublineage should be included. We collected three Fc2 viruses as candidates and conducted comparative tests. Results indicated that A/equine/Carlow/2011 (H3N8) is not suitable, because of its unstable antigenic characteristics. A comparison between A/equine/Richmond/1/2007 (H3N8) (Richmond/07) and A/equine/Yokohama/aq13/2010 (H3N8) (Yokohama/10) in eggs showed that they shared equal growth properties. Immunogenicity test in mice showed that Yokohama/10 induced higher HI antibody titers than Richmond/07. Therefore, we concluded that Yokohama/10 was the most suitable strain. PMID:28163276
Vaccines are the best defense available against infectious diseases. Vaccine safety is of major focus for regulatory bodies, vaccine manufacturers, public health authorities, health care providers and the public as vaccines are often given to healthy children and adults as well as to pregnant woman. Safety assessment is critical at all stages of vaccine development. Effective, clear and consistent communication of the risks and benefits of vaccines and advocacy during all stages of clinical research (including the preparation, approvals, conduct of clinical trials through the post marketing phase) is critically important. This needs to be done for all major stakeholders (e.g. community members, Study Team, Health Care Providers, Ministry of Health, Regulators, Ethics Committee members, Public Health Authorities and Policy Makers). Improved stakeholder alignment would help to address some of the concerns that may affect the clinical research, licensing of vaccines and their wide-spread use in immunization programs around the world.
Ormen, Bahar; Türker, Nesrin; Vardar, Ilknur; Kaptan, Figen; El, Sibel; Ural, Serap; Kaya, Fatih; Coşkun, Nejat Ali
The aims of this study were to evaluate the attitudes towards H1N1 vaccination and to determine the safety and side effects following 2009 pandemic influenza A (H1N1) vaccination. Pandemic influenza vaccine had been administered to the healthcare personnel in our research and training hospital in December 2009. The rate being vaccinated was established as 40% (800/2000). Four months following vaccination, the opinions about vaccination were asked to the healthcare workers, and also side effects were questioned to the vaccinated group. Two different questionnaires (for vaccinated and unvaccinated subjects) were delivered to the volunteers who agreed to participate in the study. Demographic features, reasons related to being vaccinated or not, were questioned. The vaccinated group was also questioned for the presence of chronic diseases, previous vaccinations (pandemic/seasonal influenza), local or systemic reactions that develop after vaccination. A total of 332 volunteers participated in the questionnaire. Of them 247 (74.4%) were vaccinated and 85 (25.6%) were unvaccinated. Male/female ratio of the participants was 1.2, and 55.7% of them were older than 30-year-old. Most of the participants (82.8%) were highly educated (high school and faculty-graduated). Vaccination rates were found statistically significant in advanced age group compared to young adults (p= 0.042); in male gender compared to females (p= 0.001) and in parents compared to subjects who didn't have children (p= 0.021). Vaccination rates were observed to be higher (57.5%) in non-medical staff (cleaning employers, administrative personnel, etc.) than the physicians (29.1%) and nurses (13.4%), and the rate was also high (54.7%) in personnel who worked in intensive care units, emergency department and administrative units than the personnel who worked in the clinics of internal medicine (22.3%) and surgery (23.1%) (p= 0.001). The most important causes of rejecting vaccination were being afraid of the
Evans, David; Cauchemez, Simon; Hayden, Frederick G
The availability of immunogenic, licensed H5N1 vaccines and the anticipated development of vaccines against "swine" influenza A(H1N1) have stimulated debate about the possible use of these vaccines for protection of those exposed to potential pandemic influenza viruses and for immunization or "priming" of populations in the so-called "prepandemic" (interpandemic) era. However, the safety of such vaccines is a critical issue in policy development for wide-scale application of vaccines in the interpandemic period. For example, wide-scale interpandemic use of H5N1 vaccines could lead to millions of persons receiving vaccines of uncertain efficacy potentially associated with rare severe adverse events and against a virus that may not cause a pandemic. Here, we first review aspects of the 1976 National Influenza Immunization Programme against "swine flu" and its well-documented association with Guillain-Barré syndrome as a case study illustration of a suspected vaccine-associated severe adverse event in a mass interpandemic immunization setting. This case study is especially timely, given the recent spread of a novel influenza A(H1N1) virus in humans in Mexico and beyond. Following this, we examine available safety data from clinical trials of H5N1 vaccines and briefly discuss how vaccine safety could be monitored in a postmarketing surveillance setting.
Poland, Gregory A; Fleming, Douglas M; Treanor, John J; Maraskovsky, Eugene; Luke, Thomas C; Ball, Emma M A; Poland, Caroline M
Both seasonal and pandemic influenza cause considerable morbidity and mortality globally. In addition, the ongoing threat of new, unpredictable influenza pandemics from emerging variant strains cannot be underestimated. Recently bioCSL (previously known as CSL Biotherapies) sponsored a symposium 'New Wisdom to Defy an Old Enemy' at the 4th Influenza Vaccines for the World Congress in Valencia, Spain. This symposium brought together a renowned faculty of experts to discuss lessons from past experience, novel influenza vaccine developments, and new methods to increase vaccine acceptance and coverage. Specific topics reviewed and discussed included new vaccine development efforts focused on improving efficacy via alternative administration routes, dose modifications, improved adjuvants, and the use of master donor viruses. Improved safety was also discussed, particularly the new finding of an excess of febrile reactions isolated to children who received the 2010 Southern Hemisphere (SH) trivalent inactivated influenza vaccine (TIV). Significant work has been done to both identify the cause and minimize the risk of febrile reactions in children. Other novel prophylactic and therapeutic advances were discussed including immunotherapy. Standard IVIg and hIVIg have been used in ferret studies and human case reports with promising results. New adjuvants, such as ISCOMATRIX™ adjuvant, were noted to provide single-dose, prolonged protection with seasonal vaccine after lethal H5N1 virus challenge in a ferret model of human influenza disease. The data suggest that adjuvanted seasonal influenza vaccines may provide broader protection than unadjuvanted vaccines. The use of an antigen-formulated vaccine to induce broad protection between pandemics that could bridge the gap between pandemic declaration and the production of a homologous vaccine was also discussed. Finally, despite the availability of effective vaccines, most current efforts to increase influenza vaccine coverage
We evaluated protection conferred by mucosal vaccination with replication competent adenovirus (RCA)-free recombinant adenovirus expressing a codon-optimized avian influenza (AI) H5 gene (AdTW68.H5ck). Commercial layer-type chicken groups were singly vaccinated ocularly at 5 days of age, or singly v...
A comprehensive review of avian influenza (AI) control methods has been completed. From 2002-2010, over 113 billion doses of AI vaccine were used in poultry in 15 countries. The majority of vaccine (over 90%) was used in China while significant amounts were used in Egypt, Indonesia, and Vietnam. ...
more seasonal vaccine than any other country, some stakeholders told us that low vaccination rates can decrease incentives for manufacturers to...of U.S.-Licensed Manufacturers of Seasonal Influenza Vaccine and Number of Doses Produced and Distributed for the 2000–01 through 2010–11 Influenza... Seasons 24 Table 7: Influenza Vaccine Production Process Using Egg-Based Technology 38 Table 8: Additional Potential Benefits of Adjuvants 43
As Product Development Partnerships (PDPs) emerge and evolve in response to the need for vaccines, this paper re-examines the oldest and most successful PDP in the vaccine field; that which year after year, produces and reinvents influenza vaccines. This paper describes the influenza vaccine production and innovation system and reviews some of its most recent major innovations. Innovation in this system is a result of collaborative partnerships between various actors from both the public and private sector. It is argued that the influenza vaccine innovation system is a Product Development Partnership (PDP), be it an unconventional one, with a central coordination role allocated to the WHO rather than a private company or charitable/not for profit entity. The unusual structure of this PDP overcomes some of the organizational issues surrounding vaccine research and production faced by other documented PDPs. These are first, the need to coordinate knowledge flow via an effective knowledge broker. Second, the need to build in-house capacity and fund essential research and elements of production where private partners find involvement too risky or costly.
Ping, Jihui; Lopes, Tiago J.S.; Nidom, Chairul A.; Ghedin, Elodie; Macken, Catherine A.; Fitch, Adam; Imai, Masaki; Maher, Eileen A.; Neumann, Gabriele; Kawaoka, Yoshihiro
Vaccination is one of the most cost-effective ways to prevent infection. Influenza vaccines propagated in cultured cells are approved for use in humans, but their yields are often suboptimal. Here, we screened A/Puerto Rico/8/34 (PR8) virus mutant libraries to develop vaccine backbones (defined here as the six viral RNA segments not encoding haemagglutinin and neuraminidase) that support high yield in cell culture. We also tested mutations in the coding and regulatory regions of the virus, and chimeric haemagglutinin and neuraminidase genes. A combination of high-yield mutations from these screens led to a PR8 backbone that improved the titres of H1N1, H3N2, H5N1 and H7N9 vaccine viruses in African green monkey kidney and Madin–Darby canine kidney cells. This PR8 backbone also improves titres in embryonated chicken eggs, a common propagation system for influenza viruses. This PR8 vaccine backbone thus represents an advance in seasonal and pandemic influenza vaccine development. PMID:26334134
Randomized, controlled, multicenter study of the immunogenicity and safety of a fully liquid combination diphtheria-tetanus toxoid-five-component acellular pertussis (DTaP5), inactivated poliovirus (IPV), and haemophilus influenzae type b (Hib) vaccine compared with a DTaP3-IPV/Hib vaccine administered at 3, 5, and 12 months of age.
Vesikari, Timo; Silfverdal, Sven Arne; Boisnard, Florence; Thomas, Stéphane; Mwawasi, Grace; Reynolds, Donna
This study compared the levels of immunogenicity and safety of diphtheria-tetanus toxoid-five-component acellular pertussis (DTaP(5)), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) (DTaP(5)-IPV-Hib) and DTaP(3)-IPV/Hib vaccines for study participants 3, 5, and 12 months of age. Post-dose 3 noninferiority criteria comparing DTaP(5)-IPV-Hib to DTaP(3)-IPV/Hib using rates of seroprotection were demonstrated against diphtheria, tetanus, and polio types 1 to 3, but not for polyribosylribitol phosphate (PRP). While PRP did not meet noninferiority criteria, the seroprotection rate and geometric mean concentration (GMC) were high, indicating a clinically robust immune response. GMCs or titers for other antigens (including pertussis) and the safety profiles were generally similar between groups. Fully liquid DTaP(5)-IPV-Hib can be administered using the 3-, 5-, and 12-month vaccination schedule. (This study has been registered at ClinicalTrials.gov under registration no. NCT00287092.).
Randomized, Controlled, Multicenter Study of the Immunogenicity and Safety of a Fully Liquid Combination Diphtheria–Tetanus Toxoid–Five-Component Acellular Pertussis (DTaP5), Inactivated Poliovirus (IPV), and Haemophilus influenzae Type b (Hib) Vaccine Compared with a DTaP3-IPV/Hib Vaccine Administered at 3, 5, and 12 Months of Age
Silfverdal, Sven Arne; Boisnard, Florence; Thomas, Stéphane; Mwawasi, Grace; Reynolds, Donna
This study compared the levels of immunogenicity and safety of diphtheria–tetanus toxoid–five-component acellular pertussis (DTaP5), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) (DTaP5-IPV-Hib) and DTaP3-IPV/Hib vaccines for study participants 3, 5, and 12 months of age. Post-dose 3 noninferiority criteria comparing DTaP5-IPV-Hib to DTaP3-IPV/Hib using rates of seroprotection were demonstrated against diphtheria, tetanus, and polio types 1 to 3, but not for polyribosylribitol phosphate (PRP). While PRP did not meet noninferiority criteria, the seroprotection rate and geometric mean concentration (GMC) were high, indicating a clinically robust immune response. GMCs or titers for other antigens (including pertussis) and the safety profiles were generally similar between groups. Fully liquid DTaP5-IPV-Hib can be administered using the 3-, 5-, and 12-month vaccination schedule. (This study has been registered at ClinicalTrials.gov under registration no. NCT00287092.) PMID:23966556
Chan, Candice Yuen-Yue; Tambyah, Paul Anantharajah
Vaccination is the principal means to reduce the impact of influenza infection. Effective vaccination programs require a reliable and safe production system. Traditionally, influenza vaccines are produced in embryonated chicken eggs. Over the last two decades, new cell culture-derived vaccines have been licensed and manufactured, and other vaccines are still in various phases of development. Vero cells have been used for the development of a wide variety of vaccines including influenza vaccines. Pandemic and avian influenza vaccines derived from Vero cells have been shown to be well tolerated and immunogenic in animal and Phase I-II clinical studies. A Phase III randomized, double-blind, placebo-controlled trial of a trivalent influenza vaccine produced in Vero-cell culture was conducted in 7250 adults aged 18-49 years. Overall protective efficacy for antigenically matched influenza vaccine was 78.5%. The vaccine was well tolerated with no treatment-related serious adverse events and compared favorably with egg-derived vaccines from previous trials. Vero-cell-derived influenza vaccines have the potential to be an important parts of the influenza vaccine strategy, especially if an avian-derived strain becomes predominant or the demand outstrips the capacity of egg-based production systems.
Moore, Dorothy L
The Canadian Paediatric Society continues to encourage annual influenza vaccination for ALL children and youth ≥6 months of age. Recommendations from the National Advisory Committee on Immunization for the 2015/2016 influenza season include some important changes: Children and adolescents with neurological or neurodevelopmental disorders were added to the list of individuals considered to be at high risk for severe influenza.Quadrivalent influenza vaccines are recommended preferentially over trivalent vaccines for use in children and youth.An adjuvanted trivalent inactivated influenza vaccine is now available for use in children six to 23 months of age. PMID:26526862
Montomoli, Emanuele; Khadang, Baharak; Piccirella, Simona; Trombetta, Claudia; Mennitto, Elisa; Manini, Ilaria; Stanzani, Valerio; Lapini, Giulia
In the 20th century, three influenza pandemics killed approximately 100 million people. The traditional method of influenza vaccine manufacturing is based on using chicken eggs. However, the necessity of the availability of millions of fertile eggs in the event of a pandemic has led research to focus on the development of cell culture-derived vaccines, which offer shorter lead-in times and greater flexibility of production. So far, the cell substrates being evaluated and in use include Vero, Madin-Darby canine kidney, PER.C6 and insect cells. However, Vero cells are the most widely accepted among others. This review introduces briefly the concepts of advanced cell culture-derived influenza vaccine production and highlights the advantages of these vaccines in terms of efficiency, speed and immunogenicity based on the clinical data obtained from different studies.
... Biological Products for Swine Influenza Vaccines AGENCY: National Institutes of Health, Public Health Service... methods of use as Veterinary Influenza Vaccines. Sustained outbreaks of highly pathogenic influenza in animals increase the risk of reassortment and adaption to humans. This technology describes DNA...
Peltola, Heikki; Pelkonen, Tuula; Bernardino, Luis; Monteiro, Lurdes; Silvestre, Silvia da Conceição; Anjos, Elizabete; Cruzeiro, Manuel Leite; Pitkäranta, Anne; Roine, Irmeli
In Angola during 2003-2012, we detected Haemophilus influenzae in 18% of 2,634 and 26% of 2,996 bacteriologically positive pleural or cerebrospinal fluid samples, respectively, from children. After vaccination launch in 2006, H. influenzae empyema declined by 83% and meningitis by 86%. Severe H. influenzae pneumonia and meningitis are preventable by vaccination.
Tamas, Ferenc; Jankovics, Istvan
With the recent pandemic of influenza A (H1N1) and vaccine shortages, there has been considerable interest in developing influenza vaccines with reduced doses, allowing for increased production capacity. Here we report a prospective, randomized, double-blind, single-center clinical trial of a reduced-dose whole-virion inactivated, adjuvanted influenza vaccine in adult and elderly volunteers. A total of 234 subjects, including 120 adults (18 to 60 years of age) and 114 elderly subjects (>60 years of age) were enrolled to receive either 6 μg or the conventional 15-μg dose of seasonal trivalent influenza vaccines. The subjects were followed for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition testing. The subjects developed antibody responses against the seasonal influenza A virus H1N1 and H3N2 strains, as well as the seasonal influenza B virus included in the vaccines. Single doses of 6 μg fulfilled licensing criteria for seasonal influenza vaccines. No significant differences in rates of seroconversion or seroprotection or in geometric mean titers were found between the two dosage levels. All adverse events were rare, mild, and transient. We found that the present reduced-dose vaccine is safe and immunogenic in healthy adult and elderly subjects and triggers immune responses that comply with licensing criteria. PMID:22219315
Shropshire, Ali M.; Brent-Hotchkiss, Renee; Andrews, Urkovia K.
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…
characterization capabilities within the DoD • Culture, HAI , PCR (battery), Sequencing, Serology (HI, MN) – Rapid sharing of results with CDC and/or...unspecified vaccination types Collect 2 Swabs from Each Pt with “Influenza-Like Illness” (ILI) Follow DoD case definition for ILI: • FEVER ≥100.5°F
Alberta-Wszolek, Lauren; Mousette, Alyse M; Mahalingam, Meera; Levin, Nikki A
Linear IgA Bullous Dermatosis (LABD) is an immune-mediated subepidermal vesiculobullous eruption characterized by linear deposits of IgA at the basement membrane zone. Most cases are idiopathic but medications, infections, and malignancies have also been reported to induce LABD. We report the case of a 54-year-old woman who developed LABD shortly after receiving an influenza vaccination.
Wahlen, Mongeon Kari J; Bessette, Richard R; Bernard, Matthew E; Springer, Donna J; Benson, Catherine A
Vaccine distribution is an essential component of any healthcare organization's pandemic influenza plan. Variables surrounding distribution in these circumstances are often difficult to anticipate and require careful consideration. The 2009 H1N1 influenza pandemic provided organizations with an opportunity to test current models and overall organizational readiness for the next influenza pandemic. This article describes the experiences at a large, midwestern, multispecialty medical system in responding to the unique circumstances surrounding distribution of the 2009 H1N1 influenza vaccine. We discuss challenges, variables to consider when choosing a vaccine distribution model, institutional response, and lessons learned.
Inactivated influenza vaccines do not provide cross-protection to diverse antigenic strains that could be circulating or suddenly arise in a population. It is desirable to vaccinate at a young age to provide maximum protection from influenza; however, maternally-derived factors (antibody or cells) c...
Recently, a new avian influenza vaccine was licensed by USDA for use in the United States for protection of commercial poultry. The vaccine is a recombinant herpes virus of turkeys expressing the hemagglutinin gene of an H5 subtype avian influenza virus belonging to the 2.2 clade of the H5N1 highly ...
Subramanian, Rahul; Graham, Andrea L.; Grenfell, Bryan T.; Arinaminpathy, Nimalan
Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to be updated continually to keep up to date with this antigenic change, but emerging ‘universal’ vaccines—targeting more conserved components of the influenza virus—offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, in terms of cumulative incidence and rates of antigenic evolution of seasonal influenza? What are their potential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenic evolution of influenza in a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage, the duration and breadth of immunity raised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in vaccination
Zarnitsyn, Vladimir G.; Sullivan, Sean P.; Compans, Richard W.; Prausnitz, Mark R.; Skountzou, Ioanna
Background Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN) coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge. Methodology/Principal Findings Inactivated A/Aichi/2/68 (H3N2) influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5×LD50 of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM) reference immunization. Conclusions/Significance The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a
Ellis, T M; Sims, L D; Wong, H K H; Wong, C W; Dyrting, K C; Chow, K W; Leung, C; Peiris, J S M
Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) that occurred in Hong Kong up until February/March 2002 were controlled by stamping out. With endemic presence of the virus in the region and large daily importation of poultry to Hong Kong, the Administration considered that further risk management measures, in addition to improved biosecurity and enhanced surveillance, were necessary to prevent outbreaks. Vaccination using a killed H5N2 vaccine was evaluated over a 12-month period in the district with the last HPAI cases in the early 2002 outbreak. The vaccination trial showed that farmer-administered killed H5N2 vaccine produced suitable flock antibody responses; vaccinated birds were protected against H5N1 HPAI virus challenge and excreted significantly less H5N1 virus; and vaccination was able to control virus excretion in flocks during field outbreaks. Universal vaccination of local chicken farms was introduced in June 2003 and by the end of 2003 all chickens entering the live poultry markets in Hong Kong were vaccinated by killed H5N2 vaccine. In addition to vaccination, an enhanced biosecurity programme on farms and in live poultry markets and a comprehensive surveillance programme in poultry, wild birds, recreation park birds and pet birds were in place. Vaccination use and performance is closely monitored. This programme was successful in protecting local farms and live poultry markets from H5N1 outbreaks during the regional H5N1 outbreaks in 2004.
Kassianos, George; Blank, Patricia; Falup-Pecurariu, Oana; Kuchar, Ernest; Kyncl, Jan; De Lejarazu, Raul Ortiz; Nitsch-Osuch, Aneta; van Essen, Gerrit A
Currently there is no influenza vaccination guidance for European general practitioners. Furthermore, although the European Council recommends a target seasonal influenza vaccination rate of 75% in the elderly (65 years and above) and in anyone aged >6 months with a chronic medical condition, there remain wide discrepancies throughout Europe. A harmonised guideline regarding not only vaccination strategy but also for the consistent diagnosis of influenza across Europe is essential to support a common approach for the implementation of seasonal influenza vaccination across Europe. This document is based on pre-existing guidelines available in the UK and Netherlands and has been approved by a group of European experts for use throughout Europe. As well as providing a standardised influenza diagnosis, it also reviews the current recommendations for influenza vaccination, the types of vaccine available, the contraindications, vaccine use in special populations (in pregnancy, children, and in those with egg allergy), and concomitant administration with other vaccines. The effectiveness, safety, and timing of the seasonal influenza vaccine are also reviewed. A second section provides practical guidance for general practitioners for the implementation of a seasonal influenza vaccination program, including the selection and notification of those eligible for vaccination, as well as suggestions for the organisation of a vaccination programme. Finally, suggested responses to common patient misconceptions and frequently asked questions are included. The aim of this article is to harmonise the diagnosis of seasonal influenza and the approach of European general practitioners to seasonal influenza vaccination in order to better identify influenza outbreaks and to move towards reaching the target vaccination rate of 75% throughout Europe.
Kassianos, George; Blank, Patricia; Falup-Pecurariu, Oana; Kuchar, Ernest; Kyncl, Jan; De Lejarazu, Raul Ortiz; Nitsch-Osuch, Aneta; van Essen, Gerrit A
Currently there is no influenza vaccination guidance for European general practitioners. Furthermore, although the European Council recommends a target seasonal influenza vaccination rate of 75% in the elderly (65 years and above) and in anyone aged >6 months with a chronic medical condition, there remain wide discrepancies throughout Europe. A harmonised guideline regarding not only vaccination strategy but also for the consistent diagnosis of influenza across Europe is essential to support a common approach for the implementation of seasonal influenza vaccination across Europe. This document is based on pre-existing guidelines available in the UK and Netherlands and has been approved by a group of European experts for use throughout Europe. As well as providing a standardised influenza diagnosis, it also reviews the current recommendations for influenza vaccination, the types of vaccine available, the contraindications, vaccine use in special populations (in pregnancy, children, and in those with egg allergy), and concomitant administration with other vaccines. The effectiveness, safety, and timing of the seasonal influenza vaccine are also reviewed. A second section provides practical guidance for general practitioners for the implementation of a seasonal influenza vaccination program, including the selection and notification of those eligible for vaccination, as well as suggestions for the organisation of a vaccination programme. Finally, suggested responses to common patient misconceptions and frequently asked questions are included. The aim of this article is to harmonise the diagnosis of seasonal influenza and the approach of European general practitioners to seasonal influenza vaccination in order to better identify influenza outbreaks and to move towards reaching the target vaccination rate of 75% throughout Europe. PMID:27540408
Hofstetter, Annika M; Barrett, Angela; Stockwell, Melissa S
The Advisory Committee on Immunization Practices (ACIP) recommends that certain children under 9 years of age receive two influenza vaccine doses in a season for optimal protection. Recent data indicate that many of these children fail to receive one or both of these needed doses. Contributing factors to under-vaccination of this population remain unclear. Caregivers of children aged 6 months-8 years requiring two influenza vaccine doses in the 2010-2011 season were identified from households enrolled in four urban Head Start programs. Recruitment and survey administration were conducted between March and June 2011. The impact of caregiver, provider, and practice-based factors on influenza vaccine receipt was assessed using bivariate and multivariable logistic regression analyses. Caregivers (n = 128) were predominantly mothers, Latina, Spanish-speaking, and non-U.S. born. Few children received one (31 %) or both (7 %) influenza vaccine doses. Caregivers who discussed influenza vaccination with providers were more likely to know their child needed two doses (55 vs. 35 %, p < 0.05) and have a fully vaccinated child (11 vs. 0 %, p < 0.05). Among caregivers whose child received the first dose, those who reported being told when to return for the second dose were also more likely to have a fully vaccinated child (35 vs. 0 %, p = 0.05). Belief in influenza vaccine effectiveness was positively associated with vaccination (p < 0.001), while safety concerns were negatively associated (p < 0.05). This study highlights the importance of provider-family communication about the two-dose regimen as well as influenza vaccine effectiveness and safety.
Gicquelais, Rachel E.; Safi, Haytham; Butler, Sandra; Smith, Nathaniel; Haselow, Dirk T.
Background: Influenza is a major cause of seasonal viral respiratory illness among school-aged children. Accordingly, the Arkansas Department of Health (ADH) coordinates >800 school-based influenza immunization clinics before each influenza season. We quantified the relationship between student influenza vaccination in Arkansas public schools…
Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.
Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse
In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.
Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi
Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Areas covered: Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Expert opinion: Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence. PMID:25689872
Wiersma, Lidewij C. M.; Rimmelzwaan, Guus F.; de Vries, Rory D.
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
Cheng, Allen C; Brown, Simon; Waterer, Grant; Holmes, Mark; Senenayake, Sanjaya; Friedman, N Deborah; Hewagama, Saliya; Simpson, Graham; Wark, Peter; Upham, John; Korman, Tony; Dwyer, Dominic; Wood-Baker, Richard; Irving, Louis; Bowler, Simon; Kotsimbos, Tom; Kelly, Paul
Influenza is mostly a mild, self-limiting infection and severe infection requiring hospitalisation is uncommon. Immunisation aims to reduce serious morbidity and mortality. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 15 sites across all states and territories in Australia. This study reports on the epidemiology of hospitalisation with confirmed influenza, estimate vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2012 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with influenza confirmed by nucleic acid detection. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 9 April to 31 October 2012, 1,231 patients were admitted with confirmed influenza at the 15 FluCAN sentinel hospitals. Of these, 47% were more than 65 years of age, 8% were Indigenous Australians, 3% were pregnant and 76% had chronic co-morbidities. Influenza A was detected in 83% of patients. Vaccination coverage was calculated from the vaccination status of 1,216 test negative controls and was estimated at 77% in patients 65 years or over and 61% in patients with chronic comorbidities. Vaccination effectiveness was estimated at 41% (95% CI: 28%, 51%, P<0.001). Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. The study results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza during the 2012 season.
García, Amos; Ortiz de Lejarazu, Raúl; Reina, Jordi; Callejo, Daniel; Cuervo, Jesús; Morano Larragueta, Raúl
ABSTRACT Influenza has a major impact on healthcare systems and society, but can be prevented using vaccination. The World Health Organization (WHO) currently recommends that influenza vaccines should include at least two virus A and one virus B lineage (trivalent vaccine; TIV). A new quadrivalent vaccine (QIV), which includes an additional B virus strain, received regulatory approval and is now recommended by several countries. The present study estimates the cost-effectiveness of replacing TIVs with QIV for risk groups and elderly population in Spain. A static, lifetime, multi-cohort Markov model with a one-year cycle time was adapted to assess the costs and health outcomes associated with a switch from TIV to QIV. The model followed a cohort vaccinated each year according to health authority recommendations, for the duration of their lives. National epidemiological data allowed the determination of whether the B strain included in TIVs matched the circulating one. Societal perspective was considered, costs and outcomes were discounted at 3% and one-way and probabilistic sensitivity analyses were performed. Compared to TIVs, QIV reduced more influenza cases and influenza-related complications and deaths during periods of B-mismatch strains in the TIV. The incremental cost-effectiveness ratio (ICER) was 8,748€/quality-adjusted life year (QALY). One-way sensitivity analysis showed mismatch with the B lineage included in the TIV was the main driver for ICER. Probabilistic sensitivity analysis shows ICER below 30,000€/QALY in 96% of simulations. Replacing TIVs with QIV in Spain could improve influenza prevention by avoiding B virus mismatch and provide a cost-effective healthcare intervention. PMID:27184622
Heikkinen, Terho; Booy, Robert; Campins, Magda; Finn, Adam; Olcén, Per; Peltola, Heikki; Rodrigo, Carlos; Schmitt, Heinz-Josef; Schumacher, Fabian; Teo, Stephen; Weil-Olivier, Catherine
Influenza is often regarded as an illness of the elderly portion of the population because most of the excess mortality associated with influenza epidemics occurs in that age group. However, evidence derived from a large number of clinical studies carried out in different countries and various settings has clearly demonstrated that the burden of influenza is also substantial in children. The attack rates of influenza during annual epidemics are consistently highest in children, and young children are hospitalized for influenza-related illnesses at rates comparable to those for adults with high-risk conditions. Especially among children younger than 3 years of age, influenza frequently predisposes the patient to bacterial complications such as acute otitis media. Children also serve as the main transmitters of influenza in the community. A safe and effective vaccine against influenza has been available for decades, but the vaccine is rarely used even for children with high-risk conditions. Despite several existing problems related to influenza vaccination of children, the current evidence indicates that the advantages of vaccinating young children would clearly outweigh the disadvantages. Considering the total burden of influenza in children, children younger than 3 years of age should be regarded as a high-risk group for influenza, analogously with the age-based definition of high risk among persons 65 years of age or older. Annual influenza vaccination should be recommended to all children from 6 months to 3 years of age.
The negative impact of high pathogenicity avian influenza virus (HPAIV) infection on egg production and deposition of virus in eggs, as well as any protective effect of vaccination, is unknown. Individually housed non-vaccinated, sham-vaccinated and inactivated H5N9 vaccinated once or twice adult Wh...
Furman, David; Jojic, Vladimir; Kidd, Brian; Shen-Orr, Shai; Price, Jordan; Jarrell, Justin; Tse, Tiffany; Huang, Huang; Lund, Peder; Maecker, Holden T; Utz, Paul J; Dekker, Cornelia L; Koller, Daphne; Davis, Mark M
Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to identifying such markers, we used influenza vaccination in 30 young (20–30 years) and 59 older subjects (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation. Using machine learning, we identified nine variables that predict the antibody response with 84% accuracy. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health. PMID:23591775
Zhang, Yan-Yang; Tang, Xue-Feng; Du, Chang-Hui; Wang, Bin-Bing; Bi, Zhen-Wang; Dong, Bi-Rong
ABSTRACT The purpose of this study was to perform a meta-analysis comparing the effectiveness of influenza vaccination alone versus influenza plus pneumococcal dual vaccination for the prevention of pneumonia and mortality in adults ≥ 65 years of age. Medline, Cochrane, CENTRAL, EMBASE, and Google Scholar databases were searched. Inclusion criteria were: 1) Randomized controlled trials (RCTs), 2-arm prospective studies, or retrospective cohort studies; 2) Patients were ≥ 65 years of age with or without chronic respiratory disease; 3) Patients received the influenza vaccine alone or dual pneumococcal and influenza vaccination; 4) Results included incidence of recurrent respiratory tract infections, length of hospital stay, and overall mortality rate. The outcomes were pneumonia and all-cause mortality rates. Of 142 studies identified in the database searches, 6 were ultimately included in the systematic review, and 5 were included in meta-analysis. The number of patients that received the influenza vaccination alone ranged from 211 to 29,346 (total = 53,107), and the number that received influenza+pneumococcal vaccination ranged from 246 to 72,107 (total = 102,068). Influenza+pneumococcal vaccination was associated with a significantly lower pneumonia rate than influenza vaccination alone (relative risk [RR] = 0.835, 95% confidence interval [CI]: 0.718–0.971, P = 0.019), and with a significantly lower all-cause mortality rate than influenza vaccination alone (relative risk [RR] = 0.771, 95% confidence interval [CI]: 0.707–0.842, P = 0.001). In conclusion, the results of this study support concomitant pneumococcal and influenza vaccination of the elderly as a dual vaccination strategy is associated with lower pneumonia and all-cause mortality rates. PMID:27629584
Ibuka, Yoko; Ohkusa, Yasushi; Sugawara, Tamie; Chapman, Gretchen B; Yamin, Dan; Atkins, Katherine E; Taniguchi, Kiyosu; Okabe, Nobuhiko; Galvani, Alison P
Background Contact patterns and vaccination decisions are fundamental to transmission dynamics of infectious diseases. We report on age-specific contact patterns in Japan and their effect on influenza vaccination behaviour. Methods Japanese adults (N=3146) were surveyed in Spring 2011 to assess the number of their social contacts within a 24 h period, defined as face-to-face conversations within 2 m, and gain insight into their influenza-related behaviour. We analysed the duration and location of contacts according to age. Additionally, we analysed the probability of vaccination and influenza infection in relation to the number of contacts controlling for individual's characteristics. Results The mean and median reported numbers of daily contacts were 15.3 and 12.0, respectively. School-aged children and young adults reported the greatest number of daily contacts, and individuals had the most contacts with those in the same age group. The age-specific contact patterns were different between men and women, and differed between weekdays and weekends. Children had fewer contacts between the same age groups during weekends than during weekdays, due to reduced contacts at school. The probability of vaccination increased with the number of contacts, controlling for age and household size. Influenza infection among unvaccinated individuals was higher than for those vaccinated, and increased with the number of contacts. Conclusions Contact patterns in Japan are age and gender specific. These contact patterns, as well as their interplay with vaccination decisions and infection risks, can help inform the parameterisation of mathematical models of disease transmission and the design of public health policies, to control disease transmission. PMID:26424846
... Swine Influenza Vaccine, RNA AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice... test, an unlicensed Swine Influenza Vaccine, RNA. The environmental assessment, which is based on a risk analysis prepared to assess the risks associated with the field testing of this vaccine,...
Alfred, Norma J.; Turner, James C.; David, Felicita; DeLozier, David M.; Strikas, Raymond A.
The United States experienced a shortage of influenza vaccine for the 2004-2005 influenza season. The authors surveyed college health programs to determine whether they had targeted vaccine to priority groups and knew how to reallocate remaining vaccine. They used an electronic message to distribute a Web-based survey to the members of 3…
Bulanov, V E; Ivanov, A V; Shostak, G R
Explore information about the incidence of employees of enterprises of the oil and gas industry with the influenza (SARS). The degree of influence of vaccination on the incidence of influenza, the number and structure of complications as a result of vaccination and their impact on efficiency. Evaluation of the cost-effectiveness of vaccination.
Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of cross-reactive, non-neutralizing antibody to the challenge I...
Vaccine associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with whole-inactivated influenza virus (WIV) following infection with heterologous influenza A virus (IAV). WIV vaccination elicits production of non-neutralizing antibody that is cross-reactive to the chal...
Huston, Jane E.; Mekaru, Sumiko R.; Kluberg, Sheryl; Brownstein, John S.
Objectives The goal of the HealthMap Vaccine Finder is to provide a free, comprehensive, online service where users can search for locations that offer immunizations. In this article, we describe the data and systems underlying the HealthMap Vaccine Finder (HVF) and summarize the project’s first year of operations. Methods We collected data on vaccination services from a variety of providers for 2012–2013. Data are used to populate an online, public, searchable map. Results In its first year, HVF collected information from 1256 providers representing 46 381 locations. The public Web site received 625 124 visits during the 2012–2013 influenza vaccination season. Conclusions HVF is a unique tool that connects the public to vaccine providers in their communities. During the 2012–2013 influenza season, HVF experienced significant usage and was able to respond to user feedback with new features. PMID:25880945
Feldstein, Leora R; Matrajt, Laura; Elizabeth Halloran, M; Keitel, Wendy A; Longini, Ira M
Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: (1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and (2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48-0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32-0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15mcg had the highest estimated theoretical vaccine efficacy: Dose (1) 45% (95% CI: 36-57%), 53% (95% CI: 42-63%) and 55% (95% CI: 44-64%), respectively and Dose (2) 93% (95% CI: 89-96%), 97% (95% CI: 95-98%) and 97% (95% CI: 96-100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals
Meliopoulos, Victoria A.; Wang, Wei; Lin, Xudong; Stucker, Karla M.; Halpin, Rebecca A.; Stockwell, Timothy B.; Schultz-Cherry, Stacey
propagating the virus under well-controlled laboratory conditions, we found that the FluMist vaccine backbone could regain virulence to cause severe disease in mice. The identification of the responsible substitutions and elucidation of the underlying mechanisms provide unique insights into the attenuation of influenza virus, which is important to basic research on vaccines, attenuation reversion, and replication. In addition, this study suggests that the safety of LAIVs should be closely monitored after mass vaccination and that novel strategies to continue to improve LAIV vaccine safety should be investigated. PMID:27440882
An influenza pandemic will place an enormous strain on the world's vaccine production, distribution and administration systems. Following a pandemic declaration, industry's priority will be to deliver as much vaccine in as short a timeframe as possible. In respect to this challenge, manufacturers have successfully developed antigen-sparing strategies and significantly increased production capacity, with further growth planned assuming ongoing rising demand for seasonal vaccines. The combination of these factors has the potential to closer meet global needs for vaccine supply than ever before through increased availability of pandemic and pre-pandemic vaccines. The demonstration of cross-clade reactivity with H5N1 viruses makes the concept of pre-pandemic stockpiling and vaccination a reality for this subtype. Ensuring these vaccines are made available in a timely fashion to those who need them will present significant challenges. For local authorities, national governments and international organisations this means defining vaccine allocation and procurement processes as well as strengthening, and where necessary establishing, the critical health systems and infrastructure required for vaccine deployment. For vaccine producers this means addressing the technical and logistical issues associated with supply. This includes working with regulators to streamline key procedures, including generic labelling and batch release, while establishing flexibility in supply formats, including bulk and finished products, to maximise the speed of delivery. Similarly, the deployment of large quantities of vaccines in an emergency situation requires appropriate transport infrastructure and the distribution of associated medical supplies. As well as addressing these issues, specific consideration must be given to the logistics and storage aspects associated with stockpiling pre-pandemic vaccines. Finally, mutually agreed contractual arrangements between manufacturers and governments
Phippard, Alba E; Kimura, Akiko C; Lopez, Karla; Kriner, Paula
Hispanics are less likely to receive the influenza vaccine compared to other racial and ethnic groups in the US. Hispanic residents of the US-Mexico border region may have differing health beliefs and behaviors, and their cross-border mobility impacts disease control. To assess beliefs and behaviors regarding influenza prevention and control among border populations, surveys were conducted at border clinics. Of 197 respondents, 34 % reported conditions for which vaccination is indicated, and travel to Mexico was common. Few (35 %) believed influenza could make them 'very sick', and 76 % believed they should take antibiotics to treat influenza. Influenza vaccine awareness was high, and considered important, but only 36 % reported recent vaccination. The belief that influenza vaccination is 'very important' was strongly associated with recent vaccination; "Didn't think about it" was the most common reason for being un-vaccinated. Misconceptions about influenza risk, prevention and treatment were common in this Hispanic border population; improved educational efforts and reminder systems could impact vaccination behaviors.
Caini, Saverio; Andrade, Winston; Badur, Selim; Balmaseda, Angel; Barakat, Amal; Bella, Antonino; Bimohuen, Abderrahman; Brammer, Lynnette; Bresee, Joseph; Bruno, Alfredo; Castillo, Leticia; Ciblak, Meral A.; Clara, Alexey W.; Cohen, Cheryl; Cutter, Jeffery; Daouda, Coulibaly; de Lozano, Celina; De Mora, Domenica; Dorji, Kunzang; Emukule, Gideon O.; Fasce, Rodrigo A.; Feng, Luzhao; Ferreira de Almeida, Walquiria Aparecida; Guiomar, Raquel; Heraud, Jean-Michel; Holubka, Olha; Huang, Q. Sue; Kadjo, Herve A.; Kiyanbekova, Lyazzat; Kosasih, Herman; Kusznierz, Gabriela; Lara, Jenny; Li, Ming; Lopez, Liza; Mai Hoang, Phuong Vu; Pessanha Henriques, Cláudio Maierovitch; Matute, Maria Luisa; Mironenko, Alla; Moreno, Brechla; Mott, Joshua A.; Njouom, Richard; Nurhayati; Ospanova, Akerke; Owen, Rhonda; Pebody, Richard; Pennington, Kate; Puzelli, Simona; Quynh Le, Mai thi; Razanajatovo, Norosoa Harline; Rodrigues, Ana; Rudi, Juan Manuel; Tzer Pin Lin, Raymond; Venter, Marietjie; Vernet, Marie-Astrid; Wangchuk, Sonam; Yang, Juan; Yu, Hongjie; Zambon, Maria; Schellevis, François; Paget, John
Introduction Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate. PMID:27031105
Keller-Stanislawski, Brigitte; Englund, Janet A; Kang, Gagandeep; Mangtani, Punam; Neuzil, Kathleen; Nohynek, Hanna; Pless, Robert; Lambach, Philipp; Zuber, Patrick
Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus. This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.
Iqbal, Shahed; Li, Rongxia; Gargiullo, Paul; Vellozzi, Claudia
Some studies reported an increased risk of Guillain-Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000-2009) for GBS, and pneumonia and influenza (P&I) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004-2005 through the 2008-2009 influenza seasons (August-May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and P&I temporal clusters were identified using scan statistics. The association between P&I and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression. Vaccine coverage increased over the years (from 19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly P&I and GBS hospitalizations was observed (Spearman's correlation coefficient=0.7016, p<0.0001). A significant (p=0.001) cluster of P&I hospitalizations during December 2004-March 2005 overlapped a significant (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005. After accounting for effects of monthly vaccine coverage and age, P&I hospitalization was significantly associated (p<0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the
Souza, Thiago Moreno L; Santini-Oliveira, Marilia; Martorelli, Andressa; Luz, Paula M; Vasconcellos, Mauricio T L; Giacoia-Gripp, Carmem B W; Morgado, Mariza; Nunes, Estevão P; Lemos, Alberto S; Ferreira, Ana C G; Moreira, Ronaldo I; Veloso, Valdiléa G; Siqueira, Marilda; Grinsztejn, Beatriz; Camacho, Luiz A B
HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination.
Swayne, David E
There are 30 recorded epizootics of H5 or H7 high pathogenicity avian influenza (HPAI) from 1959 to early 2012. The largest of these epizootics, affecting more birds and countries than the other 29 epizootics combined, has been the H5N1 HPAI, which began in Guangdong China in 1996, and has killed or resulted in culling of over 250 million poultry and/or wild birds in 63 countries. Most countries have used stamping-out programs in poultry to eradicate H5N1 HPAI. However, 15 affected countries have utilized vaccination as a part of the control strategy. Greater than 113 billion doses were used from 2002 to 2010. Five countries have utilized nationwide routine vaccination programs, which account for 99% of vaccine used: 1) China (90.9%), 2) Egypt (4.6%), 3) Indonesia (2.3%), 4) Vietnam (1.4%), and 5) Hong Kong Special Administrative Region (< 0.01%). Mongolia, Kazakhstan, France, The Netherlands, Cote d'Ivoire, Sudan, North Korea, Israel, Russia, and Pakistan used < 1% of the avian influenza (AI) vaccine, and the AI vaccine was targeted to either preventive or emergency vaccination programs. Inactivated AI vaccines have accounted for 95.5% of vaccine used, and live recombinant virus vaccines have accounted for 4.5% of vaccine used. The latter are primarily recombinant Newcastle disease vectored vaccine with H5 influenza gene insert. China, Indonesia, Egypt, and Vietnam implemented vaccination after H5N1 HPAI became enzootic in domestic poultry. Bangladesh and eastern India have enzootic H5N1 HPAI and have not used vaccination in their control programs. Clinical disease and mortality have been prevented in chickens, human cases have been reduced, and rural livelihoods and food security have been maintained by using vaccines during HPAI outbreaks. However, field outbreaks have occurred in vaccinating countries, primarily because of inadequate coverage in the target species, but vaccine failures have occurred following antigenic drift in field viruses within China, Egypt
Kang, Hee Sun; De Gagne, Jennie C; Kim, Jung-Hee
Following our study of attitudes, barriers, and intentions concerning the influenza vaccination among pregnant women in South Korea, we discovered that women displaying a more positive attitude toward the influenza vaccination were more likely to receive it during their pregnancy. We also found that attitudes toward vaccination were more positive among vaccinated pregnant women than among those who were unvaccinated. Furthermore, women showed a greater intention to get vaccinated if a clinician, rather than friends, recommended it. The major perceived barriers to receiving an influenza vaccination were being pregnant, fearing harm to the baby, feeling healthy, and thinking it is unnecessary.
de Perio, Marie A.; Wiegand, Douglas M.; Brueck, Scott E.
BACKGROUND Influenza can spread among students, teachers, and staff in school settings. Vaccination is the most effective method to prevent influenza. We determined 2012–2013 influenza vaccination coverage among school employees, assessed knowledge and attitudes regarding the vaccine, and determined factors associated with vaccine receipt. METHODS We surveyed 412 (49%) of 841 employees at 1 suburban Ohio school district in March 2013. The Web-based survey assessed personal and work characteristics, vaccine receipt, and knowledge and attitudes regarding the vaccine. RESULTS Overall, 238 (58%) respondents reported getting the 2012–2013 influenza vaccine. The most common reason for getting the vaccine was to protect oneself or one’s family (87%). Beliefs that the vaccine was not needed (32%) or that it was not effective (21%) were the most common reasons for not getting it. Factors independently associated with vaccine receipt were having positive attitudes toward the vaccine, feeling external pressure to get it, and feeling personal control over whether to get it. CONCLUSIONS Influenza vaccine coverage among school employees should be improved. Messages encouraging school employees to get the vaccine should address misconceptions about the vaccine. Employers should use methods to maximize employee vaccination as part of a comprehensive influenza prevention program. PMID:25117893
Influenza A (H3N2) viruses were the predominant viruses isolated in the United States and worldwide during 1999-2000. This was the third consecutive year that influenza A/Sydney/05/97-like (H3N2) viruses were the most prevalent viruses isolated in the United States. Influenza activity in the United States was similar to the previous two seasons, although mortality measurements attributed to pneumonia and influenza (P&I) were unusually high. Overall, the 1999-2000 influenza vaccine was well matched to circulating influenza viruses. The 2000-01 influenza season will be the first for which influenza vaccination is recommended for all persons aged > or =50 years. This report summarizes surveillance for influenza in the United States and worldwide during the 1999-2000 influenza season, describes the composition of the 2000-01 influenza vaccine, and highlights changes in the recommendations for prevention and control of influenza.
Hensley, Scott E.
Seasonal influenza vaccine strains are routinely updated when influenza viruses acquire mutations in exposed regions of the hemagglutinin and neuraminidase glycoproteins. Ironically, although thousands of viral isolates are sequenced each year, today's influenza surveillance community places less emphasis on viral genetic information and more emphasis on classical serological assays when choosing vaccine strains. Here, I argue that these classical serological assays are oversimplified and that they fail to detect influenza mutations that facilitate escape of particular types of human antibodies. I propose that influenza vaccine strains should be updated more frequently even when classical serological assays fail to detect significant antigenic alterations. PMID:25108824
McAnerney, Johanna M; Walaza, Sibongile; Tempia, Stefano; Blumberg, Lucille; Treurnicht, Florette K; Madhi, Shabir A; Valley-Omar, Ziyaad; Cohen, Cheryl
Trivalent seasonal influenza vaccine effectiveness during the 2015 season in South Africa was assessed using a test-negative case control study design. Influenza A(H1N1)pdm09 was the dominant circulating strain. Overall influenza vaccine coverage was 3.2% (29/899). The vaccine effectiveness estimate, against any influenza virus infection, adjusted for age, underlying conditions and timing within season was 46.2% (95% CI: -23.5 to 76.5), and 53.6% (95% CI: -62.6 to 80.3) against influenza A(H1N1)pdm09.
Edwards, Frances; Masick, Kevin D; Armellino, Donna
Achieving high vaccination rates of health care personnel (HCP) is critical in preventing influenza transmission from HCP to patients and from patients to HCP; however, acceptance rates remain low. In 2013, New York State adopted the flu mask regulation, requiring unvaccinated HCP to wear a mask when in areas where patients are present. The purpose of this study assessed the impact of the flu mask regulation on the HCP influenza vaccination rate. A 13-question survey was distributed electronically and manually to the HCP to examine their knowledge of influenza transmission and the influenza vaccine and their personal vaccine acceptance history and perception about the use of the mask while working if not vaccinated. There were 1,905 respondents; 87% accepted the influenza vaccine, and 63% were first-time recipients who agreed the regulation influenced their vaccination decision. Of the respondents who declined the vaccine, 72% acknowledge HCP are at risk for transmitting influenza to patients, and 56% reported they did not receive enough information to make an educated decision. The flu mask protocol may have influenced HCP's choice to be vaccinated versus wearing a mask. The study findings supported that HCP may not have adequate knowledge on the morbidity and mortality associated with influenza. Regulatory agencies need to consider an alternative approach to increase HCP vaccination, such as mandating the influenza vaccine for HCP.
Palache, Abraham; Oriol-Mathieu, Valerie; Fino, Mireli; Xydia-Charmanta, Margarita
Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults ≥65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine
Maroof, Asher; Yorgensen, Yvonne M.; Li, Yufeng; Evans, Jay T.
Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2)) generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4+IL-17A+TNFα+). Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development PMID:24465206
Prestel, Jürgen; Volkers, Peter; Mentzer, Dirk; Lehmann, Helmar C; Hartung, Hans-Peter; Keller-Stanislawski, Brigitte
Purpose A prospective, epidemiologic study was conducted to assess whether the 2009 pandemic influenza A(H1N1) vaccination in Germany almost exclusively using an AS03-adjuvanted vaccine (Pandemrix) impacts the risk of Guillain–Barré syndrome (GBS) and its variant Fisher syndrome (FS). Methods Potential cases of GBS/FS were reported by 351 participating hospitals throughout Germany. The self-controlled case series methodology was applied to all GBS/FS cases fulfilling the Brighton Collaboration (BC) case definition (levels 1–3 of diagnostic certainty) with symptom onset between 1 November 2009 and 30 September 2010 reported until end of December 2010. Results Out of 676 GBS/FS reports, in 30 cases, GBS/FS (BC levels 1–3) occurred within 150 days following influenza A(H1N1) vaccination. The relative incidence of GBS/FS within the primary risk period (days 5–42 post-vaccination) compared with the control period (days 43–150 post-vaccination) was 4.65 (95%CI [2.17, 9.98]). Similar results were found when stratifying for infections within 3 weeks prior to onset of GBS/FS and when excluding cases with additional seasonal influenza vaccination. The overall result of temporally adjusted analyses supported the primary finding of an increased relative incidence of GBS/FS following influenza A(H1N1) vaccination. Conclusions The results indicate an increased risk of GBS/FS in temporal association with pandemic influenza A(H1N1) vaccination in Germany. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24817531
Wicker, S; Rabenau, H F; Gottschalk, R; Krause, G; McLennan, S
Despite decades of effort to encourage healthcare workers (HCWs) to be immunized against influenza, vaccination levels remain insufficient in Germany, with only one in five HCWs receiving the annual influenza vaccination. To prevent nosocomial influenza outbreaks and to ensure the protection of patients and HCWs, new approaches to increase vaccination rates are needed. The experience in the USA has shown that declination forms have increased vaccination coverage. One possible approach for Germany would be a combination of declination forms with the exclusive use of vaccinated staff in defined areas. This approach would respect a HCWs decision to refuse medical treatment, while at the same time protecting vulnerable patients. In addition, the influenza vaccination rates of HCWs should be collected in order to evaluate the implementation of vaccination policies. Similar to the setting of desired vaccination coverage for the chronically ill, a clearly defined vaccination goal should be established for HCWs.
Gany, Francesca; Rau-Murthy, Rohini; Mujawar, Imran
The Healthy People 2020 influenza immunization goal is 80% for non-institutionalized adults 18-64. However, vaccination rates remain stubbornly low. Culturally tailored approaches to communities with poor vaccine uptake are necessary. Taxi drivers are at risk for influenza and its complications, could serve as vectors for influenza infection, and could be an effective vaccination target to enhance herd immunity of the urban population. To the best of our knowledge, this is the first study related to influenza vaccination among taxi drivers. The NYC Taxi Network surveyed a convenience sample of 53 taxi drivers to understand vaccination barriers. Only 17% had been vaccinated. Results informed a pilot tailored workplace intervention, which resulted in vaccinations for 44% of unvaccinated drivers. The study revealed that older drivers were more likely to be vaccinated than younger drivers, while the most common barrier to immunization was that drivers thought vaccination was 'not necessary'.
Newall, Anthony T; Dehollain, Juan Pablo
It is important to consider the value for money offered by existing elderly influenza vaccination programs, particularly as doubts persist about the magnitude of the effectiveness of such programs. An informative approach to explore the value of vaccination is to consider what vaccine efficacy would be required for a program to be considered cost-effective. To estimate the cost-effectiveness of the current elderly (65+ years) influenza vaccination program in Australia, we modelled how the hypothetical removal of vaccination would increase current disease burden estimates depending on alternative vaccine efficacy assumptions. The base-case results of the analysis found that the existing elderly vaccination program is likely to be cost-effective (under A$50,000 per quality-adjusted life year gained) if the vaccine efficacy is above ∼30%. This study offers reassurance that the influenza vaccination of elderly Australians is likely to offer value for money.
... below are examples of some of the different methods that researchers have used to examine thimerosal safety in vaccines. Researchers have looked at very large groups, such as all children born in a six- ...
Wong, Terianne M; Ross, Ted M
Influenza vaccine design has changed considerably with advancements in bioinformatics and computational biology. Improved surveillance efforts provide up-to-date information about influenza sequence diversity and assist with monitoring the spread of epidemics and vaccine efficacy rates. The advent of next-generation sequencing, epitope scanning and high-throughput analysis all help decipher influenza-associated protein interactions as well as predict immune responsiveness based on host genetic diversity. Computational approaches are utilized in nearly all aspects of vaccine design, from modeling, compatibility predictions, and optimization of antigens in various platforms. This overview discusses how computational techniques strengthen vaccine efforts against highly diverse influenza species.
Mandelboim, Michal; Glatman-Freedman, Aharona; Drori, Yaron; Sherbany, Hilda; Pando, Rakefet; Sefty, Hanna; Zadka, Hila; Shohat, Tamar; Keller, Nathan; Mendelson, Ella
The seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. Nasopharyngeal samples of vaccinated and non-vaccinated patients presenting with Influenza-like-illness (ILI) were collected from over 20 outpatient clinics located in different geographic parts of Israel and were tested for the presence of influenza viruses (influenza A and influenza B). Here we show, that in the 2014-2015 season, the vaccine that included the A/Texas/50/2012 H3N2 virus was ineffective. Significant numbers of individuals vaccinated with the 2014-2015 vaccine, of all ages, were infected with influenza A (H3N2), manifesting similar symptoms as the non-vaccinated group. We further demonstrate that the Israeli circulating influenza A(H3N2) virus was different than that included in the 2014-2015 northern hemisphere vaccine, and that antibodies elicited by this vaccine were significantly less efficient in neutralizing influenza A(H3N2) infection. PMID:26716420
Basta, Nicole E; Chao, Dennis L; Halloran, M Elizabeth; Matrajt, Laura; Longini, Ira M
Vaccinating school-aged children against influenza can reduce age-specific and population-level illness attack rates. Using a stochastic simulation model of influenza transmission, the authors assessed strategies for vaccinating children in the United States, varying the vaccine type, coverage level, and reproductive number R (average number of secondary cases produced by a typical primary case). Results indicated that vaccinating children can substantially reduce population-level illness attack rates over a wide range of scenarios. The greatest absolute reduction in influenza illness cases per season occurred at R values ranging from 1.2 to 1.6 for a given vaccine coverage level. The indirect, total, and overall effects of vaccinating children were strong when transmission intensity was low to intermediate. The indirect effects declined rapidly as transmission intensity increased. In a mild influenza season (R = 1.1), approximately 19 million influenza cases could be prevented by vaccinating 70% of children. At most, nearly 100 million cases of influenza illness could be prevented, depending on the proportion of children vaccinated and the transmission intensity. Given the current worldwide threat of novel influenza A (H1N1), with an estimated R of 1.4-1.6, health officials should consider strategies for vaccinating children against novel influenza A (H1N1) as well as seasonal influenza.
Surichan, Somchaiya; Wirachwong, Ponthip; Supachaturas, Wutichai; Utid, Kanchala; Theerasurakarn, Sompone; Langsanam, Pimsuk; Lakornrach, Pattharachai; Nitisaporn, Ladda; Chansikkakorn, Chanpen; Vangkanonta, Wilak; Kaweepornpoj, Ruangchai; Poopipatpol, Kittisak; Thirapakpoomanunt, Sit; Srichainak, Somchai; Artavatkun, Witit; Chokevivat, Vichai; Wibulpolprasert, Suwit
In 2005, a year after highly pathogenic avian influenza outbreaks in Thailand, the Thai Government issued a National Strategy Plan for Pandemic Influenza Preparedness, a major objective of which was the domestic production of seasonal influenza vaccine. It was considered that sustained influenza vaccine production was the best guarantee of a pandemic vaccine in the event of a future pandemic. The Government decided to provide funds to establish an industrial-scale influenza vaccine production plant, and gave responsibility for this challenging project to the Government Pharmaceutical Organization (GPO). In 2007, with support from the World Health Organization (WHO), the GPO started to develop egg-based, trivalent inactivated influenza vaccine (IIV) in a renovated pilot plant. In early 2009, during the second year of the project, the GPO turned its attention to develop a pandemic live attenuated influenza vaccine (PLAIV) against the influenza A (H1N1) virus. By December 2010, the H1N1 PLAIV had successfully completed Phase II clinical trials and was awaiting registration approval from the Thai Food and Drug Administration (TFDA). The GPO has also started to develop an H5N2 PLAIV, which is expected to enter clinical trials in January 2011. The next step in 2011 will be the development and clinical evaluation of seasonal LAIV. To meet the needs of the national seasonal influenza vaccination programme, the GPO aims to produce 2 million doses of trivalent IIV in 2012 and progressively increase production to the maximum annual capacity of 10 million doses. This article relates how influenza vaccine production capacity was developed and how major challenges are being met in an expeditious manner, with strong local and global commitment.
Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier
Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases.
Ren, Zhenghua; Lu, Zhongzheng; Wang, Lei; Huo, Zeren; Cui, Jianhua; Zheng, Tingting; Dai, Qing; Chen, Cuiling; Qin, Mengying; Chen, Meihua; Yang, Rirong
H9N2 subtype avian influenza viruses are widespread in domestic poultry, and vaccination remains the most effective way to protect the chicken population from avian influenza pandemics. Currently, egg-based H9N2 influenza vaccine production has several disadvantages and mammalian MDCK cells are being investigated as candidates for influenza vaccine production. However, little research has been conducted on low pathogenic avian influenza viruses (LPAIV) such as H9N2 replicating in mammalian cells using microcarrier beads in a bioreactor. In this study, we present a systematic analysis of a safe H9N2 influenza vaccine derived from MDCK cells for protecting chickens against influenza virus infection. In 2008, we isolated two novel H9N2 influenza viruses from chickens raised in southern China, and these H9N2 viruses were adapted to MDCK cells. The H9N2 virus was produced in MDCK cells in a scalable bioreactor, purified, inactivated, and investigated for use as a vaccine. The MDCK-derived H9N2 vaccine was able to induce high titers of neutralizing antibodies in chickens of different ages. Histopathological examination, direct immunofluorescence, HI assay, CD4(+)/CD8(+) ratio test, and cytokine evaluation indicated that the MDCK-derived H9N2 vaccine evoked a rapid and effective immune response to protect chickens from influenza infection. High titers of H9N2-specific antibodies were maintained in chickens for 5 months, and the MDCK-derived H9N2 vaccine had no effects on chicken growth. The use of MDCK cells in bioreactors for LPAIV vaccine production is an attractive option to prevent outbreaks of LPAIV in poultry.
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
Jürgenssen, O; Moritz, A; Liehl, E; Bachmayer, H
A new influenza subunit vaccine which contains only hemagglutinin and neuraminidase antigens was investigated for reactogenicity and immunogenicity in children aged between three and 15 years. Children under six years of age received either 500 IU or 1000 IU of the commercial vaccine, those aged from six to 15 years either 1000 IU or 2000 IU. The vaccines contained the virus strains recommended by the World Health Organisation for the vaccination season 1976/77. In a double blind study the vaccinees were allocated at random to the different dosage groups. The children were examined for reactions by the vaccinating physician 24 hours after vaccination. Serum hemagglutination inhibiting antibody titers were determined before vaccination and four weeks after vaccination. In the younger age-group additional antibody determination was made two weeks after a booster injection. A very low rate of side-reactions was observed in all dosage groups. The increase of the antigen content was not associated with a higher rate of side reactions. After the first vaccination a significant rise of antibody titers could be observed in all children. After the booster injection a further increase of these antibody titers was observed. The response of the younger age group to the dosages 500 and 100 IU did not different significantly. In contrast, in the older age group the increase of the dosage from 1000 to 2000 IU was connected with a better immune response. This was especially marked in the antibody titers against the influenza B-strain virus.
Zielonka, T M; Szymańczak, M; Jakubiak, J; Nitsch-Osuch, A; Życińska, K
Despite intensive recommendations, influenza vaccination rate in medical staff in Poland ranges from about 20 % in physicians to 10 % in nurses. The objective of this work was to assess the influence of hospital influenza vaccination campaign directed toward health care workers, combined with dispensing free of charge vaccine, on vaccination rate. The campaign was conducted by the Hospital Infection Control Team of the Czerniakowski Hospital in Warsaw, Poland, separately for physicians, nurses, and physiotherapists. Overall, 37 % of medical staff were vaccinated, including 55 % of physicians and 21 % of nurses. Concerning physicians, the greatest vaccination rate was in the orthopedic (80 %) and ophthalmology units (73 %), whereas the lowest rate was in the intensive care (22 %) and neurology units (20 %). Concerning nurses, the greatest vaccination rate was in those working in the outpatient (40 %) and emergency units (29 %), whereas the lowest rate was in the ophthalmology (6 %) and surgery units (11 %). We conclude that the professional knowledge campaign combined with the incentive of free of charge vaccine substantially raises the vaccination rate among medical staff.
The history of the 1957/58 Asian flu in Germany is systematically presented for the first time. The focus is on flu vaccination, which is discussed as a yardstick of the perception of the pandemic. International expertise on influenza virology was predominantly based in Anglo-Saxon countries. German microbiologists issued no clear recommendation for preventative vaccination until 1960. Instead, quinine was relied upon as the traditional medicinal prophylaxis. Antibiotics were more frequently administered. In East Germany, little fuss was made over the Asian flu. In line with the authorities' social hygiene orientation, vaccination was accepted as a matter of principle. In the Federal Republic and West Berlin, the population rejected the vaccination largely. It was seen as a scandal that many employees were on sick leave because of the flu, thus adversely affecting the economy.
Simpson, Jacqueline K; Patalay, Rakesh; Francis, Nicholas; Roberts, Nerys
Wells syndrome is a rare disorder of unknown etiology. Precipitants include insect bites, infections, medications, malignancies, and vaccinations. Possible mechanisms include hypersensitivity reactions to antigens. There are four reports in the literature of Wells syndrome precipitated by vaccinations (hepatitis B vaccine, tetanus vaccine, tetanus-diptheria vaccine and triple antigen vaccine). We present a further case of Wells syndrome in a 22-month-old child after influenza vaccine as a novel trigger not previously reported.
Laskowski, M.; Xiao, Y.; Charland, N.; Moghadas, S. M.
Ongoing research and technology developments hold the promise of rapid production and large-scale deployment of strain-specific or cross-protective vaccines for novel influenza viruses. We sought to investigate the impact of early vaccination on age-specific attack rates and evaluate the outcomes of different vaccination strategies that are influenced by the level of single or two-dose vaccine-induced protections. We developed and parameterized an agent-based model for two population demographics of urban and remote areas in Canada. Our results demonstrate that there is a time period before and after the onset of epidemic, during which the outcomes of vaccination strategies may differ significantly and are highly influenced by demographic characteristics. For the urban population, attack rates were lowest for children younger than 5 years of age in all vaccination strategies. However, for the remote population, the lowest attack rates were obtained for adults older than 50 years of age in most strategies. We found that the reduction of attack rates following the start of vaccination campaigns during the epidemic depends critically on the disease transmissibility, suggesting that for a sufficiently high transmissibility, vaccine delivery after the onset of epidemic has little or no effect, regardless of the population demographics. PMID:26658016
The neuraminidase protein of influenza viruses is a surface glycoprotein that has enzymatic activity to remove sialic acid, the viral receptor, from both viral and host proteins. The removal of sialic acid from viral proteins plays a key role in the release of the virus from the cell by preventing ...
Cargnelutti, Diego Esteban; Sánchez, María Victoria; Mattion, Nora Marta; Scodeller, Eduardo Alberto
In pursuit of better influenza vaccines, many strategies are being studied worldwide. An attractive alternative is the generation of a broadly cross-reactive vaccine based on the induction of cytotoxic T-lymphocytes (CTL) directed against conserved internal antigens of influenza A virus. The feasibility of this approach using recombinant viral vectors has recently been demonstrated in mice and humans by several research groups. However, similar results might also be achieved through immunization with viral proteins expressed in a prokaryotic system formulated with the appropriate adjuvants and delivery systems. This approach would be much simpler and less expensive. Recent results from several laboratories seem to confirm this is as a valid option to be considered. PMID:23337287
Jindra, Christoph; Huber, Bettina; Shafti-Keramat, Saeed; Wolschek, Markus; Ferko, Boris; Muster, Thomas; Brandt, Sabine; Kirnbauer, Reinhard
Persistent infection with high-risk human papillomavirus (HPV) types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs)-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live-attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-γ ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c.) prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease. PMID:26381401
Background To optimize the vaccination coverage rates in the general population, the status of coverage rates and the reasons for non-vaccination need to be understood. Therefore, the objective of this study was to assess the changes in influenza vaccination coverage rates in the general population before and after the 2009 influenza pandemic (2008/2009, 2009/2010, and 2010/2011 seasons), and to determine the reasons for non-vaccination. Methods In January 2011 we conducted a multi-stage sampling, retrospective, cross-sectional survey of individuals in Beijing who were ≥ 18 years of age using self-administered, anonymous questionnaires. The questionnaire consisted of three sections: demographics (gender, age, educational level, and residential district name); history of influenza vaccination in the 2008/2009, 2009/2010, and 2010/2011 seasons; and reasons for non-vaccination in all three seasons. The main outcome was the vaccination coverage rate and vaccination frequency. Differences among the subgroups were tested using a Pearson’s chi-square test. Multivariate logistic regression was used to determine possible determinants of influenza vaccination uptake. Results A total of 13002 respondents completed the questionnaires. The vaccination coverage rates were 16.9% in 2008/2009, 21.8% in 2009/2010, and 16.7% in 2010/2011. Compared to 2008/2009 and 2010/2011, the higher rate in 2009/2010 was statistically significant (χ2=138.96, p<0.001), and no significant difference existed between 2008/2009 and 2010/2011 (χ2=1.296, p=0.255). Overall, 9.4% of the respondents received vaccinations in all three seasons, whereas 70% of the respondents did not get a vaccination during the same period. Based on multivariate analysis, older age and higher level of education were independently associated with increased odds of reporting vaccination in 2009/2010 and 2010/2011. Among participants who reported no influenza vaccinations over the previous three seasons, the most commonly
Szyszko, E; Brokstad, K; Cox, R J; Hovden, A-O; Madhun, A; Haaheim, L R
Vaccination provides the most effective method of limiting the impact of influenza. Inactivated influenza vaccines are available in three formulations and more information needs to be generated on how antigen presented in different vaccine formulations influences the subsequent immune response. In the present study, we have investigated the effect of two different influenza vaccine formulations on the resulting antibody and cytokine responses and compared these responses with influenza infection. Mice were vaccinated intramuscularly with one or two doses of whole or split virus vaccine or alternatively intranasally infected with influenza virus. Lymphocytes were isolated from spleen cells and stimulated in vitro for 24 or 72 h for analysis of cytokine profile at the gene expression and at the protein level. Additionally, whole blood was collected and the serum antibody response investigated by haemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA). We found that one dose of whole virus vaccine induced higher antibody and cytokine responses and thus was more immunogenic in unprimed mice than split virus vaccine. Whole virus vaccine induced a strong IFN-gamma (type 1) immune response after one dose of vaccine and a more mixed cytokine response after the second dose. Split virus vaccine induced a type 2 response, particularly after two vaccine doses. Our results show that two doses of vaccine (both vaccine formulation) were more effective in induction of Th2 type of cytokines and thus indicate that both the formulation and also the number of vaccine doses substantially influences the magnitude and quality of the immune response.
Beck, Charles R.; McKenzie, Bruce C.; Hashim, Ahmed B.; Harris, Rebecca C.; Zanuzdana, Arina; Agboado, Gabriel; Orton, Elizabeth; Béchard-Evans, Laura; Morgan, Gemma; Stevenson, Charlotte; Weston, Rachel; Mukaigawara, Mitsuru; Enstone, Joanne; Augustine, Glenda; Butt, Mobasher; Kim, Sophie; Puleston, Richard; Dabke, Girija; Howard, Robert; O'Boyle, Julie; O'Brien, Mary; Ahyow, Lauren; Denness, Helene; Farmer, Siobhan; Figureroa, Jose; Fisher, Paul; Greaves, Felix; Haroon, Munib; Haroon, Sophie; Hird, Caroline; Isba, Rachel; Ishola, David A.; Kerac, Marko; Parish, Vivienne; Roberts, Jonathan; Rosser, Julia; Theaker, Sarah; Wallace, Dean; Wigglesworth, Neil; Lingard, Liz; Vinogradova, Yana; Horiuchi, Hiroshi; Peñalver, Javier; Nguyen-Van-Tam, Jonathan S.
Background Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. Methodology/Principal Findings Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I2 and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR] = 0.23; 95% confidence interval [CI] = 0.16–0.34; p<0.001) and laboratory confirmed influenza infection (OR = 0.15; 95% CI = 0.03–0.63; p = 0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. Conclusions/Significance Infection prevention and control strategies should recommend vaccinating immunocompromised patients
Edwards, Kate M; Burns, Victoria E; Allen, Louise M; McPhee, Jamie S; Bosch, Jos A; Carroll, Douglas; Drayson, Mark; Ring, Christopher
The immune response to vaccination in animals can be enhanced by exposure to acute stress at the time of vaccination. The efficacy of this adjuvant strategy for vaccination in humans requires investigation. The current study employed a randomised controlled trial design to examine the effects of eccentric exercise prior to influenza vaccination on the antibody and cell-mediated responses. Sixty young healthy adults (29 men, 31 women) performed eccentric contractions of the deltoid and biceps brachii muscles of the non-dominant arm (exercise group) or rested quietly (control group), and were vaccinated 6h later in the non-dominant arm. Change in arm circumference and pain were measured to assess the physiological response to exercise. Antibody titres were measured pre-vaccination and at 6- and 20-week follow-ups. Interferon-gamma in response to in vitro stimulation by the whole vaccine, an index of the cell-mediated response, was measured 8 weeks post-vaccination. Interferon-gamma responses were enhanced by exercise in men, whereas antibody titres were enhanced by eccentric exercise in women but not in men. Men showed greater increase in arm circumference after eccentric exercise than women but there was no difference in reported pain. The interferon-gamma response was positively associated with the percentage increase in arm circumference among the exercise group. Eccentric exercise exerted differential effects on the response to vaccination in men and women, with enhancement of the antibody response in women, but enhancement of the cell-mediated response in men. Eccentric exercise of the muscle at the site of vaccine administration should be explored further as a possible behavioural adjuvant to vaccination.
The interruption to the New Zealand influenza vaccine supply in 2005 (caused by a manufacturing error) greatly disrupted the annual influenza vaccination programme. The sole-tendering process used by PHARMAC was blamed by some for the crisis, which may have been alleviated by having more than one supplier. In this article, the author discusses the issues resulting from having limited options of vaccine supply. Supply problems are not limited to influenza vaccine but the tight timelines required for vaccine delivery may make it wise to secure two suppliers in future. Like all health insurance, the cost of supply redundancy will be appreciable.
Influenza A virus (IAV) remains a significant global health issue causing annual epidemics, pandemics, and sporadic human infections with highly pathogenic avian or swine influenza viruses. Current inactivated and live vaccines are the mainstay of the public health response to influenza, although vaccine efficacy is lower against antigenically distinct viral strains. The first pandemic of the twenty-first century underlined the urgent need to develop new vaccines capable of protecting against a broad range of influenza strains. Such “universal” influenza vaccines are based on the idea of heterosubtypic immunity, wherein immune responses to epitopes conserved across IAV strains can confer protection against subsequent infection and disease. T-cells recognizing conserved antigens are a key contributor in reducing viral load and limiting disease severity during heterosubtypic infection in animal models. Recent studies undertaken during the 2009 H1N1 pandemic provided key insights into the role of cross-reactive T-cells in mediating heterosubtypic protection in humans. This review focuses on human influenza to discuss the epidemiological observations that underpin cross-protective immunity, the role of T-cells as key players in mediating heterosubtypic immunity including recent data from natural history cohort studies and the ongoing clinical development of T-cell-inducing universal influenza vaccines. The challenges and knowledge gaps for developing vaccines to generate long-lived protective T-cell responses is discussed. PMID:27242800
Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies
Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse
In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6–35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3–17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4+ T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6–35 months and 3–17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158. PMID:26176592
In 2010, the Advisory Committee on Immunization Practices (ACIP) first recommended annual influenza vaccination for all persons aged ≥6 months in the United States (1). Annual influenza vaccination of all persons aged ≥6 months continues to be recommended. This document 1) describes influenza vaccine virus strains included in the U.S. seasonal influenza vaccine for 2012-13; 2) provides guidance for the use of influenza vaccines during the 2012-13 season, including an updated vaccination schedule for children aged 6 months through 8 years and a description of available vaccine products and indications; 3) discusses febrile seizures associated with administration of influenza and 13-valent pneumococcal conjugate (PCV-13) vaccines; 4) provides vaccination recommendations for persons with a history of egg allergy; and 5) discusses the development of quadrivalent influenza vaccines for use in future influenza seasons. Information regarding issues related to influenza vaccination that are not addressed in this update is available in CDC's Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010 and associated updates (1,2).
Kulkarni, Prasad S; Raut, Sidram K; Dhere, Rajeev M
A live attenuated pandemic H1N1 influenza vaccine was developed in India. A post marketing surveillance was conducted retrospectively in healthy individuals (³ 3 years) who were vaccinated intranasally around one year before. After consent, the subjects recorded adverse events developing within 42 days. Among 7565 individuals (3 - 85 years), a total of 81 solicited adverse reactions (1%) were reported in 49 subjects (0.65%). The reactions included mild to moderate respiratory symptoms. No H1N1 case was encountered during one year postvaccination. The data show the safety of the live attenuated influenza vaccine platform developed in India.