Protection against influenza hospitalizations from enhanced influenza vaccines among older adults: A systematic review and network meta-analysis.

BACKGROUND: Influenza vaccines are available to help protect persons aged ≥65 years, who experience thousands of influenza hospitalizations annually. Because some influenza vaccines may work better than others, we sought to assess benefit of high-dose (HD), adjuvanted (ADJ), and recombinant (RIV) influenza vaccines ("enhanced influenza vaccines") compared with standard-dose unadjuvanted influenza vaccines (SD) and with one another for prevention of influenza-associated hospitalizations among persons aged ≥65 years. METHODS: We searched MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library to identify randomized or observational studies published between January 1990 and October 2023 and reporting relative vaccine effectiveness (rVE) of HD, ADJ, or RIV for prevention of influenza-associated hospitalizations among adults aged ≥65 years. We extracted study data, assessed risk of bias, and conducted random-effects network meta-analysis and meta-regression. RESULTS: We identified 32 studies with 90 rVE estimates from five randomized and 27 observational studies (71,459,918 vaccinated participants). rVE estimates varied across studies and influenza seasons. Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. In observational studies, ADJ, HD, and RIV conferred modestly increased protection compared with SD (rVE ranging from 10% to 19%), with no significant differences between HD, ADJ, and RIV. With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. Meta-regression of observational studies suggested that those requiring laboratory confirmation of influenza reported greater benefit of enhanced vaccines. CONCLUSIONS: HD, ADJ, and RIV provided stronger protection than SD against influenza hospitalizations among older adults. No differences in benefit were observed in comparisons of enhanced influenza vaccines with one another.

Immunogenicity, Safety, and Efficacy of Influenza Vaccine in T2DM and T2DM with Chronic Kidney Disease.

Patients with Type 2 diabetes mellitus (T2DM) and Chronic Kidney Disease (CKD) face an increased risk of morbidity and mortality after influenza infection. Several studies have shown that the influenza vaccine effectively prevents morbidity and mortality in T2DM patients. However, there has been limited research aimed at assessing the effectiveness of the trivalent influenza vaccine in T2DM-CKD patients. This study aimed to identify Geometric Mean Titers (GMTs), seroprotection, seroconversion, safety, and efficacy. This open-label clinical trial was conducted at AMC Hospital in Bandung, West Java, Indonesia between June 2021 and July 2022. The study subjects consisted of 41 T2DM and 26 T2DM-CKD patients who were administered the trivalent influenza vaccine. There was a significant difference in the average age, with the T2DM-CKD patients being older. Median titers post-vaccination for the B/Washington virus were higher in the T2DM patients compared to the T2DM-CKD patients, and this difference was statistically significant. A majority, comprising 75.6% of the T2DM and 80.8% of the T2DM-CKD patients monitored post-influenza-vaccination, did not experience any adverse reactions. The most common reaction was the sensation of fever, with incidence rates of 12.2% in the T2DM patients and 15.4% in the T2DM-CKD patients. Furthermore, we observed that the incidence of Influenza-like Illness was highest at 7.3% in the T2DM patients and 7.7% in the T2DM-CKD patients. The trivalent influenza vaccine demonstrated equivalent safety and effectiveness in both groups.

Effect of Influenza Vaccination on Rate of Influenza Virus Infection in Chinese Military Personnel, 2015-2016: A Cluster Randomized Trial.

Influenza is a major cause of morbidity and mortality. The protective effect of a trivalent influenza vaccine (TIV) is undetermined in military personnel. We conducted an open-label, cluster randomized trial on active-duty servicemen of Beijing, Tianjin, and Shijiazhuang, who were randomly assigned to receive either a single dose of TIV or no treatment, according to cluster randomized sampling. The subjects were then followed for a maximum of six months to assess the incidence of laboratory-confirmed influenza. A total of 5445 subjects in 114 clusters received one dose of TIV before the 2015/2016 influenza season. Laboratory-confirmed influenza was identified in 18 in the vaccine group compared with 87 in the control group (6031 subjects in 114 clusters), resulting in a vaccine effectiveness (VE) of 76.4% (95%CI: 60.7 to 85.8) against laboratory-confirmed influenza. Influenza-like illness was diagnosed in 132 in the vaccine group compared with 420 in the control group, resulting in a VE of 64.1% (95%CI: 56.2 to 70.6). The estimated VE against influenza B viruses was 80.5% (95%CI: 65.6 to 88.9) and 8.6% (95%CI: -241 to 75.5) against influenza A viruses. In conclusion, the trivalent influenza vaccine is moderately effective, highly immunogenic, and generally safe to use in healthy male military servicemen.

Immunogenicity and safety of seasonal influenza vaccines in children under 3 years of age.

INTRODUCTION: Despite children aged 6-35 months developing more severe influenza infections, not all countries include influenza vaccines in their national immunization programs. AREAS COVERED: This literature review examines the efficacy, immunogenicity, and safety of seasonal trivalent influenza vaccines (TIVs) and quadrivalent influenzae vaccines (QIVs) in children 6-35 months old to determine if greater valency promotes greater protection while maintaining a similar safety profile. EXPERT OPINION: TIVs and QIVs are safe for children under 3 years old. TIVs and QIVs provided good seroprotection, and immunogenicity (GMT, SCR, and SPR) meeting recommended levels set by CHMP (European) and CBER (USA). However, as QIVs carry two influenza B strains and TIVs only one, QIVs has an overall higher seroprotection against particularly influenza B. Vaccines containing adjuncts had better immunogenicity, particularly after the first dose. Seroprotection of all vaccines lasted 12 months. Increasing the dosage from 0.25 mL to 0.5 mL did not cause more systemic or local side-effects. Further comparisons of efficacy, and wider promotion of influenza vaccines in general are required in preschool children.

The Cost-Effectiveness of Vaccination of Older Adults with an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Other Available Quadrivalent Vaccines in Germany.

Enhanced quadrivalent influenza vaccines that include an adjuvant (aQIV) or a high dose of antigen (QIV-HD), which stimulate a stronger immune response in older adults than the standard vaccine (QIVe), are now approved. The objective of this research is to compare available vaccines and determine the cost-effectiveness of immunizing persons aged 65 years and above with aQIV compared to QIVe and QIV-HD in Germany. A compartmental transmission model calibrated to outpatient visits for influenza in Germany was used to predict the number of medically attended infections using the three vaccines. The rates of hospitalizations, deaths, and other economic consequences were estimated with a decision tree using German data where available. Based on meta-analysis, the rVE of -2.5% to 8.9% for aQIV versus QIV-HD, the vaccines are similar clinically, but aQIV is cost saving compared to QIV-HD (unit cost of EUR 40.55). All results were most sensitive to changes in vaccine effectiveness. aQIV may be cost-effective compared to QIVe depending on the willingness to pay for additional benefits in Germany. As aQIV and QIV-HD are similar in terms of effectiveness, aQIV is cost saving compared to QIV-HD at current unit prices.

A Bayesian Network to Predict the Risk of Post Influenza Vaccination Guillain-Barré Syndrome: Development and Validation Study.

BACKGROUND: Identifying the key factors of Guillain-Barré syndrome (GBS) and predicting its occurrence are vital for improving the prognosis of patients with GBS. However, there are scarcely any publications on a forewarning model of GBS. A Bayesian network (BN) model, which is known to be an accurate, interpretable, and interaction-sensitive graph model in many similar domains, is worth trying in GBS risk prediction. OBJECTIVE: The aim of this study is to determine the most significant factors of GBS and further develop and validate a BN model for predicting GBS risk. METHODS: Large-scale influenza vaccine postmarketing surveillance data, including 79,165 US (obtained from the Vaccine Adverse Event Reporting System between 1990 and 2017) and 12,495 European (obtained from the EudraVigilance system between 2003 and 2016) adverse events (AEs) reports, were extracted for model development and validation. GBS, age, gender, and the top 50 prevalent AEs were included for initial BN construction using the R package bnlearn. RESULTS: Age, gender, and 10 AEs were identified as the most significant factors of GBS. The posttest probability of GBS suggested that male vaccinees aged 50-64 years and without erythema should be on the alert or be warned by clinicians about an increased risk of GBS, especially when they also experience symptoms of asthenia, hypesthesia, muscular weakness, or paresthesia. The established BN model achieved an area under the receiver operating characteristic curve of 0.866 (95% CI 0.865-0.867), sensitivity of 0.752 (95% CI 0.749-0.756), specificity of 0.882 (95% CI 0.879-0.885), and accuracy of 0.882 (95% CI 0.879-0.884) for predicting GBS risk during the internal validation and obtained values of 0.829, 0.673, 0.854, and 0.843 for area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy, respectively, during the external validation. CONCLUSIONS: The findings of this study illustrated that a BN model can effectively identify the most significant factors of GBS, improve understanding of the complex interactions among different postvaccination symptoms through its graphical representation, and accurately predict the risk of GBS. The established BN model could further assist clinical decision-making by providing an estimated risk of GBS for a specific vaccinee or be developed into an open-access platform for vaccinees' self-monitoring.

Cost-effectiveness analysis of quadrivalent seasonal influenza vaccines in Beijing: A modeling analysis.

BACKGROUND: Since 2007, Beijing has offered a free trivalent influenza vaccine (TIV) for residents aged ≥ 60 years and school students. The quadrivalent influenza vaccine (QIV) was administered to school children in 2018 and will be administered to elderly adults in the future. In addition, health care workers (HCWs) who are involved in the prevention and control of COVID-19 were included in the program in 2020. This study aimed to analyze the cost-effectiveness of a comprehensive list of combined strategies of TIV and QIV for school children, elderly adults, and HCWs to identify the most cost-effective strategy. METHODS: A decision tree was developed to compare 1-year outcomes of TIV vs. QIV in three risk groups: school children, elderly adults, and HCWs. The outcome was incremental cost per quality-adjusted life-year (QALY). Probabilistic sensitivity analyses and scenario analyses were developed to assess the robustness of the results. RESULTS: From the perspective of society, this study found that the introduction of QIVs can be cost-effective for any and all targeted groups with a willingness-to-pay threshold of 3-fold GDP per capita. Among all programs, program H (all school children, elderly adults, and HCWs received the QIV) showed a 79% probability of being cost-effective with an incremental cost-effectiveness ratio (ICER) of 13,580 (95% CI: 13,294, 13,867) US$/QALY and was the preferred option in the base case scenario. CONCLUSION: The introduction of QIVs to school children, elderly adults, or HCWs is likely to be cost-effective, either separately or collectively. The introduction of QIV to school children, elderly adults, and health care workers simultaneously showed the highest probability of being cost-effective and was the preferred option.

Serologic response to sequential vaccination with enhanced influenza vaccines: Open label randomized trial among adults aged 65-74 years.

BACKGROUND: The effects of sequential vaccination with enhanced influenza vaccines are poorly understood. We conducted an exploratory open-label study to assess serologic response to sequential vaccination in older adults. METHODS: 160 adults aged 65 through 74 years were randomized (1:1:1) to receive trivalent inactivated standard dose (SD), high-dose (HD), or MF59-adjuvanted (AD) vaccine in 2016/17. In 2017/18, HD and AD recipients received the same vaccine; SD recipients were re-randomized to HD or AD. Hemagglutination inhibition assays were performed using turkey erythrocytes against A/California/7/2009(H1N1)-like and B/Brisbane/60/2008(B/Victoria)-like in both seasons, and A/Michigan/45/2015(H1N1)-like in season 2. Microneutralization assays were performed against cell-propagated A/Hong Kong/4801/2014(H3N2)-like using MDCK-SIAT1 cells. Postvaccination geometric mean titer (GMT), percent with titer ≥ 40, and mean fold rise (MFR, ratio of postvaccination versus prevaccination titer) in season 2 were compared across groups, and ratio of MFR in season 2 versus season 1 was assessed for each strain. RESULTS: Analysis included 152 participants (55 HD â†’ HD, 58 AD â†’ AD, 19 SD â†’ HD, and 20 SD â†’ AD). Season 2 postvaccination GMTs and percent with titer ≥ 40 did not differ between HD â†’ HD and AD â†’ AD recipients for vaccine strains examined. However, a higher percent of HD â†’ HD and AD â†’ AD recipients had postvaccination titer ≥ 40 than SD â†’ AD recipients for A/H1N1 (86%-89% versus 60%) and SD â†’ AD and SD â†’ HD recipients for A/H3N2 (83%-87% versus 40%-53%). GMTs were higher in AD â†’ AD versus SD â†’ AD recipients for A/H1N1 (p = .01) and A/H3N2 (p = .002). MFRs in season 2 were low in all groups for A/H3N2 (1.5-2.2) and B/Victoria (1.7-2.3). MFR was lower in season 2 versus 1 for HD â†’ HD and AD â†’ AD recipients for all vaccine strains (1.6-3.7 versus 2.6-6.2). CONCLUSIONS: Sequential vaccination with enhanced vaccines did not reduce immunogenicity in adults aged 65 through 74 years. Serologic response to cell-propagated A/H3N2 was suboptimal for all vaccines. ClinicalTrials.gov identifier. NCT02872311.

Analysis of the adverse events following immunization with inactivated quadrivalent influenza vaccine from 2018 to 2020 in Zhejiang province, with a comparison to trivalent influenza vaccine.

OBJECTIVES: To summarize reports to the national adverse event following immunization surveillance system (NAEFISS) following inactivated quadrivalent influenza vaccine (QIV) in Zhejiang province from 2018 to 2020. METHODS: We analyzed adverse events following immunization (AEFI) reports following QIV, with a comparison, with the AEFI reports following inactivated trivalent influenza vaccine (TIV). Reporting rates of AEFI were calculated by age, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR­1.96SE >1 (standard error [SE]) was considered as positive signal. These reporting rates between vaccine types were compared through chi-square tests. RESULTS: NAEFISS received 514 AEFI reports following QIV and 536 reports following TIV, with a reporting rate of 13.66/100,000 100,000 doses/100,000 doses (χ2 = 7.11, P> .05). Of the 514 reports following QIV, 410 were vaccine product-related reactions and 51 were severe AEFI. Fever/redness/induration was the most frequent clinical diagnosis of the QIV AEFI, with a reporting rate of 12.42/100,000 doses in the age group of 3-17 years, and 12.44/100,000 doses in the age group of ≥18 years. The positive signal of QIV AEFI was observed for the allergic rash and asthma/wheezing. CONCLUSION: The present analysis did not identify any new/unexpected safety concerns. We suggested that NAEFISS continue to monitor the safety of QIV.

Prediction of post-vaccination Guillain-Barré syndrome using data from a passive surveillance system.

PURPOSE: Severe adverse events (AEs), such as Guillain-Barré syndrome (GBS) occur rarely after influenza vaccination. We identify highly associated AEs with GBS and develop prediction models for GBS using the US Vaccine Adverse Event Reporting System (VAERS) reports following trivalent influenza vaccination (FLU3). METHODS: This study analyzed 80 059 reports from the US VAERS between 1990 and 2017. Several AEs were identified as highly associated with GBS and were used to develop the prediction model. Some common and mild AEs that were suspected to be underreported when GBS occurred simultaneously were removed from the final model. The analyses were validated using European influenza vaccine AEs data from EudraVigilance. RESULTS: Of the 80 059 reports, 1185 (1.5%) were annotated as GBS related. Twenty-four AEs were identified as having strong association with GBS. The full prediction model, using age, sex, and all 24 AEs achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 85.4% (90% CI: [83.8%, 86.9%]). After excluding the nine (e.g., pruritus, rash, injection site pain) likely underreported AEs, the final AUC became 77.5% (90% CI: [75.5%, 79.6%]). Two hundred and one (0.25%) reports were predicted as of high risk of GBS (predicted probability >25%) and 84 actually developed GBS. CONCLUSION: The prediction performance demonstrated the potential of developing risk-prediction models utilizing the VAERS cohort. Excluding the likely underreported AEs sacrificed some prediction power but made the model more interpretable and feasible. The high absolute risk of even a small number of AE combinations suggests the promise of GBS prediction within the VAERS dataset.

Immunogenicity and safety of the first indigenously developed Indian tetravalent influenza vaccine (split virion) in healthy children (6 months to 17 years of age): a randomized, multicenter, phase III clinical trial.

This phase III clinical trial was conducted to evaluate the immunogenicity and safety of the Tetravalent Influenza Vaccine (Split virion) I.P. (TetIV), containing two strains each of influenza A and B, developed indigenously in the country for the first time by M/s Cadila Healthcare Limited, India for use in the pediatric population (6 months -17 years of age), and compare it to that of a licensed seasonal Trivalent Influenza Vaccine (TriIV) of Sanofi Pasteur India Private Limited, containing two influenza A and one influenza B strains. Three hundred six subjects of either sex, 6 months to 17 years of age, were randomized in a 1:1 ratio to receive either TetIV or TriIV. Immunogenicity assessments (antibodies against A/H1N1, A/H3N2, B/Phuket, and B/Brisbane) were performed using the hemagglutination inhibition assay at baseline and 28 days after the last vaccination. TetIV was found to fulfill the criteria set by the United States Food and Drug Administration on the requirements of clinical data for licensure of seasonal inactivated influenza vaccines for the pediatric population. The seroconversion rates with TetIV were 94.6% for A/H1N1, 93.9% for A/H3N2, 91.2% for B/Brisbane, and 87.2% for B/Phuket strains. TetIV showed non-inferiority and superiority in immune response, as compared to TriIV, against the shared strains and an additional B strain, respectively. Both the vaccines were tolerated well by all the study participants, and an addition of the fourth strain in TetIV did not compromise the safety as compared to that of TriIV. The most common adverse event reported in both groups was fever.

Vaccine effectiveness of live attenuated and trivalent inactivated influenza vaccination in 2010/11 to 2015/16: the SIVE II record linkage study.

BACKGROUND: There is good evidence of vaccine effectiveness in healthy individuals but less robust evidence for vaccine effectiveness in the populations targeted for influenza vaccination. The live attenuated influenza vaccine (LAIV) has recently been recommended for children in the UK. The trivalent influenza vaccine (TIV) is recommended for all people aged ≥ 65 years and for those aged < 65 years who are at an increased risk of complications from influenza infection (e.g. people with asthma). OBJECTIVE: To examine the vaccine effectiveness of LAIV and TIV. DESIGN: Cohort study and test-negative designs to estimate vaccine effectiveness. A self-case series study to ascertain adverse events associated with vaccination. SETTING: A national linkage of patient-level general practice (GP) data from 230 Scottish GPs to the Scottish Immunisation & Recall Service, Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. PARTICIPANTS: A total of 1,250,000 people. INTERVENTIONS: LAIV for 2- to 11-year-olds and TIV for older people (aged ≥ 65 years) and those aged < 65 years who are at risk of diseases, from 2010/11 to 2015/16. MAIN OUTCOME MEASURES: The main outcome measures include vaccine effectiveness against laboratory-confirmed influenza using real-time reverse-transcription polymerase chain reaction (RT-PCR), influenza-related morbidity and mortality, and adverse events associated with vaccination. RESULTS: Two-fifths (40%) of preschool-aged children and three-fifths (60%) of primary school-aged children registered in study practices were vaccinated. Uptake varied among groups [e.g. most affluent vs. most deprived in 2- to 4-year-olds, odds ratio 1.76, 95% confidence interval (CI) 1.70 to 1.82]. LAIV-adjusted vaccine effectiveness among children (aged 2-11 years) for preventing RT-PCR laboratory-confirmed influenza was 21% (95% CI -19% to 47%) in 2014/15 and 58% (95% CI 39% to 71%) in 2015/16. No significant adverse events were associated with LAIV. Among at-risk 18- to 64-year-olds, significant trivalent influenza vaccine effectiveness was found for four of the six seasons, with the highest vaccine effectiveness in 2010/11 (53%, 95% CI 21% to 72%). The seasons with non-significant vaccine effectiveness had low levels of circulating influenza virus (2011/12, 5%; 2013/14, 9%). Among those people aged ≥ 65 years, TIV effectiveness was positive in all six seasons, but in only one of the six seasons (2013/14) was significance achieved (57%, 95% CI 20% to 76%). CONCLUSIONS: The study found that LAIV was safe and effective in decreasing RT-PCR-confirmed influenza in children. TIV was safe and significantly effective in most seasons for 18- to 64-year-olds, with positive vaccine effectiveness in most seasons for those people aged ≥ 65 years (although this was significant in only one season). FUTURE WORK: The UK Joint Committee on Vaccination and Immunisation has recommended the use of adjuvanted injectable vaccine for those people aged ≥ 65 years from season 2018/19 onwards. A future study will be required to evaluate this vaccine. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88072400. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 67. See the NIHR Journals Library website for further project information.

In Scotland, a new type of influenza vaccine (live attenuated influenza vaccine), administered via the nose, was introduced in 2014/15 for all children aged between 2 and 11 years. It can be difficult to evaluate any changes in health as a result of new immunisation programmes, given that randomised controlled trials of vaccines are impractical and can also be seen as unethical. These changes are therefore typically not evaluated, making it difficult to inform future policy in this field. Observational studies can be used to assess the effects of health-care interventions without influencing the care that is provided or affecting the people who receive it. An evaluation (effectiveness and safety) of this change in the immunisation programme was conducted. The vaccine programme, an inactivated vaccine administered as an injection, for other groups for whom the evidence available is limited was also evaluated [i.e. for people aged ≥ 65 years and people aged < 65 years who have a medical condition (e.g. asthma) that puts them at risk of severe illness from influenza]. The findings support the view that the intranasal vaccine is effective and safe in preventing influenza in children. The injectable vaccine in people aged < 65 years who are more at risk of complications from flu was safe and effective. Lower effectiveness was found in people aged ≥ 65 years. Both the injectable vaccine and the intranasal vaccine have high levels of uptake in the population offered vaccination. When considering these results, the important limitation of bias in observational study designs should be noted [for instance, residual confounding, whereby it is not possible to measure a characteristic of those people receiving the vaccine (e.g. being healthier)], and this is accounted for in this analysis.

A Population-Based Propensity Score-Matched Study to Assess the Impact of Repeated Vaccination on Vaccine Effectiveness for Influenza-Associated Hospitalization Among the Elderly.

BACKGROUND: Influenza is a major cause of morbidity and mortality in the elderly worldwide. Influenza vaccination can prevent morbidity/mortality from influenza infection. A gap of 1-2 years, before an epidemic strain is recommended by the World Health Organization (WHO) to be the vaccine strain in Southeast Asia, has been reported; this results in a high rate of vaccine mismatch and excess influenza-associated morbidity. The aim of the current study was to evaluate the effect of repeated vaccination on vaccine effectiveness (VE) among the elderly in Taiwan, during years with and without early appearance of antigenically drifted strains. METHODS: A historical cohort study was conducted to evaluate the impact of repeated vaccination on the reduction of influenza-associated hospitalization among persons older than 64 years over two influenza seasons: 2007-08, with all circulating virus strains mismatched, and 2008-09, with all virus strains matched with the vaccine strains, considering four exposure effects, namely current vaccine effect, sequential vaccination effect, residual protection effect and no vaccination effect. Propensity score matching on vaccination status was performed to ensure similar baseline characteristics between the groups that received and did not receive vaccination. RESULTS: Only current-year vaccination in combination with prior history of annual revaccination significantly reduced the risk of hospitalization, with adjusted hazard ratios of 0.68 (95% CI: 0.54, 0.85) and 0.74 (95% CI: 0.57, 0.95) during the 2007-08 and 2008-09 influenza seasons, respectively. Further stratification showed that even during the 2007-08 influenza season, when all vaccinations were mismatched with the circulating strains, sequential vaccinations still significantly reduced influenza-associated hospitalization in the female population aged 68-74 and 75-84 years, with adjusted VE of 25.2% (95% CI: -9.6, 49.0%) and 36.9% (95% CI: 17.1, 52.0%), respectively. CONCLUSION: Our study supports the recommendation of annual revaccination against influenza in the elderly, even though the circulating strain of influenza virus was antigenically mismatched with the vaccine strains.

Immunogenicity and safety of MF59-adjuvanted quadrivalent influenza vaccine versus standard and alternate B strain MF59-adjuvanted trivalent influenza vaccines in older adults.

OBJECTIVE: Evaluate whether adjuvanted quadrivalent influenza vaccine (aQIV) elicits a noninferior immune response compared with a licensed adjuvanted trivalent influenza vaccine (aTIV-1; Fluad™) and aTIV-2 containing an alternate B strain, examine whether aQIV had immunological superiority for the B strain absent from aTIV comparators, and evaluate reactogenicity and safety among adults ≥65 years. METHODS: In a multicenter, double-blind, randomized controlled trial, adults ≥65 years were randomized 2:1:1 to vaccination with aQIV (n = 889), aTIV-1 (n = 445), or aTIV-2 (n = 444) during the 2017-2018 influenza season. Immunogenicity was assessed by hemagglutination inhibition (HI) assay conducted on serum samples collected before vaccination and 21 days after vaccination for homologous influenza strains. RESULTS: aQIV met non-inferiority criteria for geometric mean titer ratios (GMT ratios) and seroconversion rate (SCR) differences against aTIV. The upper bounds of the 2-sided 95% confidence interval (CI) for GMT ratios were <1.5 for all 4 strains (A/H1N1 = 1.27, A/H3N2 = 1.09, B-Yamagata = 1.08, B-Victoria = 1.08). The upper bounds of the 95% CI of the SCR differences were <10% for all 4 strains (A/H1N1 = 7.76%, A/H3N2 = 4.96%, B-Yamagata = 3.27%, B-Victoria = 2.55%). aQIV also met superiority criteria (upper bound of 95% CI for GMT ratios <1 and SCR differences <0) for B strain absent from aTIV comparators (B-Yamagata GMT ratio = 0.70, SCR difference = -8.81%; B-Victoria GMT ratio = 0.78, SCR difference = -8.11%). aQIV and aTIV vaccines were immunogenic and well-tolerated. The immunological benefit of aQIV was also demonstrated in age subgroups 65-74 years, 75-84 years, and ≥85 years and in those with high comorbidity risk scores. Reactogenicity profiles were generally comparable. CONCLUSION: aQIV induces a similar immune response as the licensed aTIV vaccine against homologous influenza strains and has a comparable reactogenicity and safety profile. Superior immunogenicity against the additional B strain was observed, indicating that aQIV could provide a broader protection than aTIV against influenza in older adults (NCT03314662).

Cost-effectiveness of quadrivalent versus trivalent influenza vaccine for elderly population in China.

BACKGROUND: Influenza-associated excess death occurred most in the elderly. We aimed to assess the cost-effectiveness of quadrivalent influenza vaccine (QIV) versus trivalent influenza vaccine (TIV) for prevention of influenza infection among elderly population in China. METHODS: A decision-analytic model was developed to compare 1-year clinical and economic outcomes of three influenza vaccination options (no vaccination, TIV, and QIV) in a hypothetical cohort of Chinese elderly aged 69 years. Outcome measures included cost, influenza infection rate, influenza-related mortality rate, quality-adjusted life-years (QALY) loss, and incremental cost-effectiveness ratio (ICER) from societal perspective. Sensitivity analyses were performed to examine the uncertainty of model inputs. RESULTS: Base-case results showed no vaccination was dominated (more costly at higher QALY loss) by TIV and QIV. QIV was more costly (USD56.29 versus USD54.28) with lower influenza infection rate (0.608 versus 0.623), mortality rate (0.00199 versus 0.00204), and QALY loss (0.01213 versus 0.01243) than TIV. QIV was cost-effective compared to TIV with ICER of 6,700 USD/QALY below the willingness-to-pay threshold (29,580 USD/QALY). One-way sensitivity analysis found the cost-effectiveness of QIV was subject to the relative risk of vaccine effectiveness of QIV versus TIV, and TIV would be cost-effective if the relative risk was below 1.05. In 10,000 Monte Carlo simulations, the probabilities of QIV, TIV, and no vaccination to be cost-effective were 86.3%, 13.7%, and 0%, respectively. CONCLUSION: QIV appears to be a cost-effective option compared to TIV and no influenza vaccination for elderly population in China.

Effectiveness of seasonal inactivated influenza vaccination in Japanese schoolchildren: an epidemiologic study at the community level.

Influenza vaccination is the most effective method for preventing influenza virus infection. The incidence of influenza is higher in schoolchildren than other age groups. This study evaluated the effectiveness of seasonal inactivated influenza vaccination (IIV) in a community population of schoolchildren during two seasons. This study was a cross-sectional survey of public schoolchildren based on data collected in the 2012/2013 and 2014/2015 seasons. The questionnaire was distributed to all public schoolchildren of target grade in a survey area, and 7945 respondents were included in the analysis. The vaccination status and influenza onset were defined based on the self-reported questionnaire by parents or guardians. Generalized linear mixed models were used to adjust clustering within schools and individual covariates and calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between vaccination status and influenza onset. The influenza incidence was higher in the 2015 than the 2013 survey (25% versus 17%), although the vaccination rates were comparable between the two seasons. Receiving one- or two-dose vaccination was more protective against influenza than non-vaccination in both the 2013 (OR, 0.77; 95%CI, 0.65-0.92) and 2015 (OR, 0.88; 95%CI, 0.75-1.02) surveys. Full vaccination was also more protective in both the 2013 (OR, 0.75; 95%CI, 0.62-0.89) and 2015 (OR, 0.86; 95%CI, 0.74-1.00) surveys. Seasonal IIV was protective against influenza for Japanese schoolchildren in a community-based real-world setting. The difference in clinical effectiveness of IIV between the two seasons was likely due to the antigenic mismatch between the circulating and vaccine strains.

Safety and immunogenicity of a split-virion quadrivalent influenza vaccine / 预防医学

Objective @# To evaluate the safety and immunogenicity of a split-virion quadrivalent influenza vaccine.@*Methods @#The healthy people aged three years or over in Wuyang County and Xiping County of Henan Province were divided into the experimental group, control group 1 and control group 2, and were vaccinated with split-virion quadrivalent influenza vaccines, split-virion trivalent influenza vaccines (without B/Victoria) and a split-virion trivalent influenza vaccines (without B/Yamagata) , respectively. The hemagglutination inhibition (HI) antibodies were detected before and after immunization. The incidence rate of adverse events following immunization (AEFI) , HI antibody positive conversion rate, the protection rate of HI antibodies and the growth of geometric mean titer (GMT) were calculated and compared with the standard of Food and Drug Administration (FDA).@*Results@#Totally 2 924 people were recruited, with 975 in the experimental group, 974 in the control group 1 and 975 in control group 2. The incidence rate of AEFI in the experimental group was 11.7%, higher than 7.9% in control group 1 and 8.8% in control group 2 (P < 0.05) during 30 minutes and 8 days after inoculation. The positive conversion rates of HI antibodies of H1N1, H3N2, By and Bv in the experimental group were 78.5%, 53.3%, 78.3% and 62.9%, respectively. The rate differences of the positive conversion rates of HI antibodies of By between the experimental group and control group 2, and of Bv between the experimental group and control group 1 were 42.1% (95%CI: 38.0%-46.2%) and 33.2% (95%CI: 28.9%-37.5%) , with both lower limits of 95%CI more than -0.10. The GMT increase of HI antibodies was more than 2.5 times in the three groups. The protective rates of HI antibodies of H1N1, H3N2, By and Bv in the experimental group were 87.7%, 98.7%, 93.6% and 77.2%, respectively. The protective rates of HI antibodies of By in control group 2 and Bv in control group 1 were 71.1% and 51.0%, both lower than those in the experimental group (P < 0.05).@*Conclusions @#After the inoculation of the quadrivalent influenza vaccine, the positive conversion rates (>40%) , protection rates (>70%) and GMT increase (>2.5 times) of HI antibodies of H1N1, H3N2, By and Bv all meet the quality standards of FDA. The safety and immunogenicity of the quadrivalent influenza vaccine are not inferior to those of the trivalent influenza vaccine.

Evaluation of Waning Immunity at 6 Months after Both Trivalent and Quadrivalent Influenza Vaccination in Korean Children Aged 6-35 Months.

BACKGROUND: The titer of influenza vaccine-induced antibodies declines over time, and younger children have lower immunogenicity and shorter duration of immunity. This study aimed to compare persistence of antibody at 6 months after influenza vaccination according to influenza virus strains, vaccine type, antigen dose, and primed status in children aged 6 to 35 months. METHODS: A total 124 healthy children aged 6 to 35 months were enrolled from September to December 2016 at 10 hospitals in Korea and randomly assigned to either a full dose of quadrivalent influenza vaccine or a half dose of trivalent influenza vaccine with Victoria B strain group. Hemagglutination inhibition antibody titers (that measure the seroprotection rates) were assessed for the recommended influenza strains at 6 months post vaccination. RESULTS: The seroprotection rates at 6 months for strains A (H1N1), A (H3N2), B/Yamagata, and B/Victoria were 88.7%, 97.4%, 36.6%, and 27.6%, respectively. The seroprotection rates for A (H1N1), A (H3N2) and B (Victoria) were 91.4%, 98.7% and 27.5% in a full dose of quadrivalent vaccine vs. 83.7%, 94.6% and 27.9% in a half dose trivalent vaccine, respectively. The seroprotection rate for the B (Yamagata) strain was 23.8% in the quadrivalent group and 14.0% in the trivalent group. CONCLUSION: Persistence of antibodies at 6 months was more favorable against the influenza A strains than against the B strains. Persistence of antibodies to additional B strain at 6 months was superior in the quadrivalent vaccine group. The immunity of primed children with different B strains was not superior to that of the unprimed group with another B strain.

Pharmacovigilance capacity strengthening for WHO prequalification: The case of the trivalent influenza vaccine manufactured by Instituto Butantan.

Instituto Butantan is a biomedical research center and vaccine manufacturer affiliated with the São Paulo State Secretary of Health in Brazil. In 2013, Instituto Butantan successfully licensed its trivalent influenza vaccine, in order to support the Brazilian National Immunization Program's influenza vaccination strategy, which was introduced in 1999. In order to respond to the increasing influenza vaccine demand worldwide, Instituto Butantan is undergoing prequalification of its trivalent influenza vaccine by the World Health Organization (WHO). A key requirement of the prequalification review was the submission of a pharmacovigilance plan, including an active surveillance evaluation, for the trivalent influenza vaccine, and proof of a functional pharmacovigilance system at Instituto Butantan. The aim of this paper is to describe the capacity strengthening process of the pharmacovigilance system at Instituto Butantan for the WHO prequalification of the trivalent influenza vaccine. This process was supported by PATH and the U.S. Federal Government Biomedical Advanced Research and Development Authority (BARDA). The key strategic axes for this capacity strengthening process included the improvement of organizational structure, human resources training, internal processes and procedures, appropriate documentation, and acquisition of an E2B compliant pharmacovigilance database. The project led to the establishment of a functional pharmacovigilance system compliant with international regulatory requirements.