Influenza Vaccine In Children Research Articles

P-612. Effectiveness of Live Attenuated and Inactivated Influenza Vaccines in Children: Data from the 2023/24 Influenza Season

Abstract Background Annual vaccination with a live attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV) is the most effective way to protect children from the burden of influenza infection, and to reduce the potential for transmission to family members and the community. Here we report vaccine effectiveness (VE) from data reported globally for LAIV and IIV in children from the 2023/24 influenza season. Methods Quadrivalent LAIV and IIV effectiveness studies conducted in children in the 2023/24 influenza season were identified from published literature and public health websites. Studies from Canada, Finland, the UK, the US, and a European-wide study in 10 countries, reporting VE data for any influenza infection (all strains), by strain type (all influenza A, A/H3N2, and A/H1N1pdm09), and by vaccination setting (primary/outpatient care and hospital) were included. Results In five studies reporting on influenza infections (all strains) in children with ages ranging from 6 months to 19 years across studies, VE estimates for LAIV ranged from 36% (95% CI: 21–48) in Finland to 65% (95% CI: 41–79) in the UK, and for IIV ranged from 59% (95% CI: 48–67) to 67% (95% CI: 48–80) in the US. When analyzed by vaccination setting, VE against any influenza, influenza A, A/H3N2, and A/H1N1pdm09 in all the included countries ranged from 36–65% for LAIV and 46–85% for IIV in children in primary/outpatient care (Figure 1). For hospitalized children, VE against any influenza, influenza A, A/H3N2, and A/H1N1pdm09 in all the included countries ranged from 25–80% for LAIV and 46–61% for IIV (Figure 2). Where available, VE data against influenza A, A/H3N2, and A/H1N1pdm09 were comparable for both LAIV and IIV in children in primary/outpatient care and hospitalized children. Conclusion VE data for the 2023/24 season from global reports show LAIV and IIV demonstrated comparable moderate protection for children against influenza infection. These early VE data were similar across the included healthcare settings of outpatient/primary care and hospitals. Disclosures Allyn R. Bandell, PharmD, AstraZeneca: Stocks/Bonds (Public Company) Chris Barker, PhD, AstraZeneca: Stocks/Bonds (Public Company) Oliver Dibben, PhD, AstraZeneca: Stocks/Bonds (Public Company)

Evaluating Families' Opinions of Routine Influenza Vaccination in Children Under 5 Years of Age in Spain.

Influenza vaccination is the main method for preventing influenza. The objectives of this study are to evaluate the opinions of families on influenza vaccination and to determine the acceptance of influenza vaccination as a routine vaccine in children under 5 years of age. The method used was a descriptive cross-sectional study based on an ad-hoc survey. Between October 2023 and January 2024, an online survey was conducted among families with children between 6 months and 14 years of age attending paediatric consultations at a health centre. A total of 388 families were surveyed. Out of these, 22.68% reported having ever vaccinated their children against influenza. The main reason for having them vaccinated was having received the recommendation from the paediatrician (68.18%). While 53.61% agreed with routine influenza vaccination, 53.09% did not intend to vaccinate their children against influenza in the 2023/24 period. The reasons for not vaccinating in 2023/24 were unawareness of the disease (29.41%), fear of unwanted effects of vaccination (27.94%) and lack of information about vaccination (19.61%). The reasons for vaccination in 2023/24 were protection of the child (81.87%), recommendation by the paediatrician (43.41%) and protection of the general population and susceptible persons (20.33%). Routine influenza vaccination is accepted by half of the parents. A lack of risk perception of the disease, concern about vaccine safety and lack of information are the main reasons for not vaccinating. It is essential to follow the health professionals' recommendation to vaccinate.

Safety and immunogenicity of full-dose quadrivalent influenza vaccine in children 6–35 months of age in China: A randomized, double-blind, clinical trial

ABSTRACT A half-dose influenza vaccine (7.5 μg hemagglutinin per strain) has been used for children under 3 years of age for a long time. However, several studies indicate that a full-dose influenza vaccine (15 μg hemagglutinin per strain) may bring more benefit to this population without increasing the risk of adverse reactions. We conducted a clinical study in children aged 6–35 months in China. Participants were randomized to receive two doses of full-dose quadrivalent influenza vaccine (F-QIV), half-dose quadrivalent vaccine (H-QIV), and two half-dose trivalent vaccines (H-TIV) in a 2:2:1:1 ratio. The safety and tolerability profile of the vaccine was evaluated for 6 months postvaccination. Hemagglutination inhibition (HI) antibody titers were measured for immunogenicity assessment. The primary objective was to assess whether the results of all vaccines met the criteria. A total of 1,980 participants were enrolled in the study. Both H-QIV and F-QIV were well tolerated after vaccination. Although the geometric mean increase (GMI), seroconversion rate (SCR), and seroprotection rate (SPR) for both H-QIV and F-QIV were achieved by the criteria, superior immunogenicity in terms of geometric mean titer (GMT) ratio was observed in F-QIV to H-QIV for A/H3N2 (GMT ratio (95% CI) of 1.37 (1.11 ~ 1.68)) and B/Yamagata (1.21 (1.05 ~ 1.39)). Antibody responses to the QIV were non-inferior to the response to the TIV for the matched strains. In conclusion, F-QIV and H-QIV were both safe and immunogenic for children. F-QIV induced a stronger immune response to influenza viruses and may provide more protection and benefit by promoting the use of F-QIV in children aged 6–35 months.

Influenza vaccination for children in Europe: The health of every child matters.

Influenza vaccination for children in Europe: The health of every child matters.

Estimating Influenza Illnesses Averted by Year-Round and Seasonal Campaign Vaccination for Young Children, Kenya.

In Kenya, influenza virus circulates year-round, raising questions about optimum strategies for vaccination. Given national interest in introducing influenza vaccination for young children 6-23 months of age, we modeled total influenza-associated illnesses (inclusive of hospitalizations, outpatient illnesses, and non‒medically attended illnesses) averted by multiple potential vaccination strategies: year-round versus seasonal-campaign vaccination, and vaccination starting in April (Southern Hemisphere influenza vaccine availability) versus October (Northern Hemisphere availability). We modeled average vaccine effectiveness of 50% and annual vaccination coverage of 60%. In the introduction year, year-round vaccination averted 6,410 total illnesses when introduced in October and 7,202 illnesses when introduced in April, whereas seasonal-campaign vaccination averted 10,236 (October) to 11,612 (April) illnesses. In the year after introduction, both strategies averted comparable numbers of illnesses (10,831-10,868 for year-round, 10,175-11,282 for campaign). Campaign-style vaccination would likely have a greater effect during initial pediatric influenza vaccine introduction in Kenya; however, either strategy could achieve similar longer-term effects.

Parental Hesitancy toward Seasonal Influenza Vaccination for Children under the Age of 18 Years and Its Determinants in the Post-Pandemic Era: A Cross-Sectional Survey among 1175 Parents in China.

Children's susceptibility to influenza increased after COVID-19 control measures were lifted. This study investigated parental hesitancy toward seasonal influenza vaccination (SIV) for children and its determinants in the post-pandemic era. An online survey of full-time adult factory workers was conducted in Shenzhen, China in December 2023. This analysis was based on 1175 parents who had at least one child under the age of 18 years. Among all parents, 37.1% were hesitant to have their index child receive SIV. Mothers exhibited lower parental hesitancy toward SIV compared to fathers (31.9% versus 41.3%, p < 0.001). After adjusting for significant background characteristics, mothers and fathers who were more satisfied with the SIV health promotion materials, perceived more severe consequences of seasonal influenza for their children, and perceived more benefits, cues to action, and self-efficacy related to their children's SIV were less likely to exhibit hesitancy toward SIV. Higher frequency of exposure to information about the increasing number of patients or severe cases due to seasonal influenza and other upper respiratory infections on social media was associated with lower parental hesitancy toward SIV among fathers but not mothers. There is a strong need to address parental hesitancy toward SIV for children in the post-pandemic era.

Effectiveness of inactivated influenza vaccine in children during the 2023/24 season: The first season after relaxation of intensive COVID-19 measures

BackgroundThe annual administration of the influenza vaccine is the most effective method for preventing influenza. We have evaluated the effectiveness of the inactivated influenza vaccine in children aged 6 months to 15 years across the seasons from 2013/2014 to 2022/2023. This study aims to investigate the effectiveness of the inactivated influenza vaccine in the 2023/2024 season, the first year following the easing of strict COVID-19 measures, and possibly the last season when only the inactivated vaccine is available on the market. MethodsAdjusted vaccine effectiveness for the 2023/2024 season was assessed using a test-negative case-control design, with results based on polymerase chain reaction and rapid influenza diagnostic tests. Vaccine effectiveness was calculated by influenza type and patient hospitalization/outpatient status. ResultsA total of 1832 children were recruited. The inactivated influenza vaccine was effective in preventing both symptomatic influenza A and B in both inpatient and outpatient settings. Overall vaccine effectiveness for influenza A was 51% (95% confidence interval [CI], 23%–69%, n = 930) in inpatient settings and 54% (95%CI, 27%–71%, n = 559) in outpatient settings. For influenza B, effectiveness was 60% (95%CI, 22%–79%, n = 859) in inpatient settings and 56% (95%CI, 26%–74%, n = 558) in outpatient settings. Analysis suggested that administering two doses enhanced effectiveness specifically against influenza B. ConclusionsThis is the first study to demonstrate influenza vaccine effectiveness in children after the relaxation of strict COVID-19 measures in Japan (2023/2024). We recommend the current inactivated vaccine for preventing both influenza A and B in children, with consideration for the potential use of two doses to enhance effectiveness against influenza B.

COVID-19 Vaccine Hesitancy in Caregivers of Hospitalized Children From 2020 Through 2023.

Data on US caregiver perceptions on coronavirus disease 2019 (COVID-19) and COVID-19 vaccination are limited. We identified trends in and associations with COVID-19 vaccine hesitancy in caregivers of hospitalized children. Cross-sectional surveys on pediatric COVID-19 disease and vaccine attitudes, behaviors, and beliefs were administered across study years (December 8, 2020-April 5, 2021, November 30, 2021-March 15, 2022, and October 26, 2022-March 15, 2023). English and Spanish-speaking caregivers of hospitalized children ages 6 months to 11 years were included. General vaccine hesitancy was assessed using the Parent Attitudes about Childhood Vaccines survey. Of 1268 caregivers from diverse backgrounds, one-third vaccinated or intended to vaccinate their child. Half endorsed fear of their child receiving the COVID-19 vaccine and were concerned the vaccine was new. Over time, more believed "the COVID-19 vaccine does not work" and fewer agreed "children who are otherwise healthy can die from COVID-19." Study season (2022-2023), older child age, higher income, child receipt of influenza vaccine, caregiver receipt of COVID-19 vaccine, and not being worried about vaccine novelty were positively associated with child vaccination. Intent to vaccinate was negatively associated with study season (2022-2023), Parent Attitudes about Childhood Vaccines score ≥50, lack of child influenza and caregiver COVID-19 vaccination, lack of fear of their child "getting COVID-19" and being "worried that the COVID-19 vaccine is new." The majority who intended to vaccinate were willing to immunize before discharge. Vaccine novelty and perceived lack of need were associated with refusal. Caregiver COVID-19 and child influenza vaccine acceptance were positively associated with COVID-19 vaccine acceptance. The inpatient setting offers the opportunity to improve vaccine uptake.

Parental knowledge, attitudes, and practices toward vaccinating their children against influenza: a cross-sectional study from China.

Influenza infection is a health burden in children, and the influenza vaccine is an important prevention strategy for flu illness. Parents play a crucial role in children's influenza vaccination. The study aimed to assess parental knowledge, attitudes, and practices (KAP) related to influenza illness for their children and explore factors that may impact their decisions. This cross-sectional study was conducted in a tertiary hospital in Guangzhou from November 2022 to April 2023. Answers to KAP questions regarding influenza illness and vaccination were summed, with a total KAP score of 20. Univariate and multivariate logistic regression models and linear regression models were conducted to explore the factors associated with influenza vaccination. The results were presented as odds ratios (ORs), β, and 95% confidence intervals (CIs). Overall, 530 parents were respondents, of whom 162 (30.56%) had vaccinated their children during the past year. The mean KAP score (standard deviation) was 13.40 (3.57). Compared to parents who reported non-vaccinated for their children in the past year, the parents who reported an influenza vaccination have higher knowledge scores, attitude scores, practice scores, and total scores. Child body mass index, parental education level (under college), parental work (part-time), and more than two family members over 60 years old were negatively correlated with knowledge score. Child health condition and knowledge score were positively correlated with attitude score. Parental age was negatively associated with attitude score. Though high awareness about influenza illness and vaccination for parents, the coverage rate of influenza vaccination in children was lower in Guangzhou. Implementing public health policies is necessary to spread knowledge about influenza illness and vaccination and to promote the practice of receiving the influenza vaccine in children. Education campaigns would help change the attitudes of parents toward vaccinating their children against the flu.

The efficacy and safety of a quadrivalent live attenuated influenza nasal vaccine in Japanese children: A phase 3, randomized, placebo-controlled study

BackgroundVaccination is the primary method of preventing influenza infection and complications in young children. We evaluated the efficacy and safety of a single dose of MEDI3250 (intranasal, quadrivalent, live attenuated influenza vaccine) in healthy Japanese children during the 2016/17 influenza season. MethodsIn this multicenter, randomized, double-blind, phase 3 study (jRCT2080223345), participants aged 2–18 years received MEDI3250 or placebo (2:1), stratified by age (2–6 years, 7–18 years). The primary and secondary endpoints were the incidence of confirmed symptomatic onset of influenza caused by a circulating wild-type strain or by a vaccine-matched strain, respectively. Safety outcomes included the incidence of adverse events (AEs) and vaccine-related AEs. ResultsOverall, 910 participants received MEDI3250 (n = 608) or placebo (n = 302). For the primary endpoint (regardless of the influenza subtype), the incidence of influenza onset was 25.5 % (MEDI3250) and 35.9 % (placebo); relative risk reduction, 28.8 % (95 % confidence interval, 12.5 %, 42.0 %). For the secondary endpoint (vaccine-matched strain), the incidence was 10.9 % (MEDI3250) and 17.2 % (placebo); relative risk reduction, 36.6 % (95 % confidence interval, 6.5 %, 56.8 %). Solicited AEs occurred in 67.6 % (MEDI3250) and 63.6 % (placebo). Most events were mild; nasal discharge was most common (59.2 % [MEDI3250] and 52.6 % [placebo]). Unsolicited AEs occurred in 36.0 % (MEDI3250) and 33.1 % (placebo). The most common unsolicited vaccine-related AE was diarrhea (2.3 %, both groups). ConclusionsMEDI3250 had a greater preventive effect against influenza onset in Japanese children than placebo; no new safety signals were observed relative to previous clinical and post-marketing studies of MEDI3250.

A Prediction Model for Identifying Seasonal Influenza Vaccination Uptake Among Children in Wuxi, China: Prospective Observational Study.

Predicting vaccination behaviors accurately could provide insights for health care professionals to develop targeted interventions. The aim of this study was to develop predictive models for influenza vaccination behavior among children in China. We obtained data from a prospective observational study in Wuxi, eastern China. The predicted outcome was individual-level vaccine uptake and covariates included sociodemographics of the child and parent, parental vaccine hesitancy, perceptions of convenience to the clinic, satisfaction with clinic services, and willingness to vaccinate. Bayesian networks, logistic regression, least absolute shrinkage and selection operator (LASSO) regression, support vector machine (SVM), naive Bayes (NB), random forest (RF), and decision tree classifiers were used to construct prediction models. Various performance metrics, including area under the receiver operating characteristic curve (AUC), were used to evaluate the predictive performance of the different models. Receiver operating characteristic curves and calibration plots were used to assess model performance. A total of 2383 participants were included in the study; 83.2% of these children (n=1982) were <5 years old and 6.6% (n=158) had previously received an influenza vaccine. More than half (1356/2383, 56.9%) the parents indicated a willingness to vaccinate their child against influenza. Among the 2383 children, 26.3% (n=627) received influenza vaccination during the 2020-2021 season. Within the training set, the RF model showed the best performance across all metrics. In the validation set, the logistic regression model and NB model had the highest AUC values; the SVM model had the highest precision; the NB model had the highest recall; and the logistic regression model had the highest accuracy, F1 score, and Cohen κ value. The LASSO and logistic regression models were well-calibrated. The developed prediction model can be used to quantify the uptake of seasonal influenza vaccination for children in China. The stepwise logistic regression model may be better suited for prediction purposes.

Epidemiological, clinical characteristics and the association between influenza vaccination, oseltamivir treatment, and complications in children with seasonal influenza

Influenza, a historical and contemporary public health challenge, is an acute respiratory infection caused mainly by influenza A or B viruses. This descriptive case series describes 194 children treated for seasonal influenza at the Department of Pediatrics, 103 Military Hospital, Vietnam Military Medical University, from May 2022 to May 2023. Influenza primarily occurred during winter and early spring, peaking in December and January, 57.2% were aged 12-60 months, boys. Vaccination coverage was limited (36.3%), especially post-COVID-19. Complications were seen in 75.3% of the cases, including febrile seizures (42.3%), bronchopneumonia (40.2%), respiratory failure (8.2%), acute myocarditis, influenza-associated encephalopathy, and septic shock. The study reveals bacterial coinfections, affected 20% of the cases, mainly by Streptococcus pneumoniae and S. aureus, and atypical bacteria Mycoplasma pneumoniae. Non-vaccinated children faced significantly higher risks of complications, oseltamivir within 48 hours reducing the risks of complications. Influenza predominantly affects 12-60 month-olds, males, and peaks annually in winter. Severe conditions stem from bacterial coinfections, emphasizing the importance of vaccination and prompt antiviral treatment to mitigate complications. The study highlights a critical need for increased vaccination, especially in the post-COVID-19 era, to manage influenza in children effectively.

Air pollutants, seasonal influenza, and acute otitis media in children: a population-based analysis using 22-year hospitalization data

BackgroundAcute otitis media (AOM) is a prevalent childhood acute illness, with 13.6 million pediatric office visits annually, often stemming from upper respiratory tract infections (URI) and affected by environmental factors like air pollution and cold seasons.MethodsHerein, we made use of territory-wide hospitalization data to investigate the relationships between meteorological factors, air pollutants, influenza infection, and AOM for children observed from 1998 to 2019 in Hong Kong. Quasi-Poisson generalized additive model, combined with a distributed-lag non-linear model, was employed to examine the relationship between weekly AOM admissions in children and weekly influenza-like illness-positive (ILI +) rates, as well as air pollutants (i.e., oxidant gases, sulfur dioxide, and fine particulate matter), while accounting for meteorological variations.ResultsThere were 21,224 hospital admissions due to AOM for children aged ≤ 15 years throughout a 22-year period. The cumulative adjusted relative risks (ARR) of AOM were 1.15 (95% CI, 1.04–1.28) and 1.07 (95% CI, 0.97–1.18) at the 95th percentile concentration of oxidant gases (65.9 ppm) and fine particulate matter (62.2 μg/m3) respectively, with reference set to their medians of concentration. The ARRs exhibited a monotone increasing trend for all-type and type-specific ILI + rates. Setting the reference to zero, the cumulative ARRs of AOM rose to 1.42 (95% CI, 1.29–1.56) at the 95th percentile of ILI + Total rate, and to 1.07 (95% CI, 1.01–1.14), 1.19 (95% CI, 1.11–1.27), and 1.22 (95% CI, 1.13–1.32) for ILI + A/H1N1, A/H3N2, and B, respectively.ConclusionsOur findings suggested that policy on air pollution control and influenza vaccination for children need to be implemented, which might have significant implications for preventing AOM in children.

Predictors of parental acceptance to live attenuated influenza vaccine for children

ABSTRACT To determine the influencing factors of Chinese parents' intention and behavior for children to receive live attenuated influenza vaccine during the 2022–2023 influenza season. A theoretical model was developed and included seven constructs, and structural equation modeling was used to test 11 hypotheses. From October 2022 to December 2023, a survey was conducted across 38 medical institutions in four Chinese cities and their subordinate districts, counties, and rural areas. Parents who accompanied their children for vaccinations were selected through a randomization process based on their child’s medical card numbers. Measures were taken to minimize method bias, including a diverse geographical representation and random sampling. The survey resulted in the collection of 936 valid responses, exceeding the recommended sample size for structural equation model analysis and providing robust statistical inferences. During the study period, 936 respondents were included in the study. Perceived ease of use was verified to be a predictor of perceived usefulness and perceived value. Perceived usefulness was verified as a predictor of perceived value and behavioral intention. Knowledge was a significant antecedent of perceived value and risk perception of influenza disease. Risk perception of influenza disease was proved to be a significant predictor of perceived value and self-reported vaccination behavior. Perceived value significantly affected behavioral intention, and behavioral intention significantly affected self-reported vaccination behavior. Six demographic variables significantly moderate the theoretical models. The low vaccination coverage of live attenuated influenza vaccine (LAIV) among children in China suggests a need for a deeper understanding of the factors that influence vaccination rates. Particularly, effective strategies are necessary from policymakers and practitioners to elevate childhood LAIV coverage.

‘It's not for the children's sake’: A qualitative inquiry into the barriers and facilitators underlying parents' decision-making for vaccinating children against influenza in Denmark

Recently, the Danish Health Authority began recommending vaccinating children aged 2–6 years against seasonal influenza, underscoring the pivotal role of children in its transmission dynamics within the wider population and the need to protect vulnerable population groups after COVID-19. Under a third followed the recommendation. For the routine Danish childhood vaccine program coverage is usually well above 90%.Through a qualitative in-depth study with 28 key informants during the 2022/2023 influenza season, we investigated the barriers and facilitators of parents' decision-making for vaccinating their children against influenza. We found that parents' decision-making was influenced by a range of factors that present barriers or facilitators at the individual or collective levels, depending on personal antecedents and family situations. We also gained insights on how COVID-19 mass vaccination shaped parents’ attitudes and awareness toward influenza vaccination, explaining why many parents who fully complied with the COVID-19 recommendations elected to opt out of influenza.The implications of these findings extend beyond the concrete context of parent's decision-making regarding influenza vaccination, contributing to our understanding of vaccine confidence in at least two ways. First, the limited public controversy regarding childhood influenza vaccination allows for a perspective onto low vaccine uptake that does not resort to the usual framing of a well-defined “crisis”. Second, the interaction between COVID-19 vaccination and the childhood influenza vaccination reveals how the massive pressure on parents to vaccinate themselves and their children against COVID-19 contributed to an erosion of vaccine confidence in general.

Comparison of the influenza vaccination coverage among high-risk people between the online registration system and walk-in service system in Bangkok, Thailand.

Until recently, the Thai national program of seasonal influenza vaccination for high-risk people has been using a walk-in service system. However, in 2020, an online registration system was introduced in Bangkok to improve vaccine coverage. This study aimed to compare the coverage of influenza vaccination between the walk-in service and online registration systems. The study participants included 374,710 Thai individuals who obtained an influenza vaccination from the national program in the Bangkok health region in 2018 (n = 162,214) and in 2020 (n = 212,496). The registration systems that were examined were the walk-in service system in 2018 and the online registration system in 2020. The characteristics of vaccine recipients and the vaccine coverage in each risk group and health facility level were compared between the two systems. Coverage comparison in Bangkok between the years 2018 and 2020 showed an increase in coverage, particularly among individuals who had an influenza vaccination at health facilities of the primary level and in the elderly and obesity groups. The coverage among children was lowest among all high-risk groups. To improve coverage in Thailand, the online registration system should be introduced in all regions. Additionally, information about influenza vaccination for children should be disseminated to parents using handbooks or by word-of-mouth from healthcare workers.

Interim 2023/2024 Season Influenza Vaccine Effectiveness in Primary and Secondary Care in the United Kingdom.

We report 2023/2024 season interim influenza vaccine effectiveness for three studies, namely, primary care in Great Britain, hospital settings in Scotland and hospital settings in England. A test negative design was used to estimate vaccine effectiveness. Estimated vaccine effectiveness against all influenzas ranged from 63% (95% confidence interval 46 to 75%) to 65% (41 to 79%) among children aged 2-17, from 36% (20 to 49%) to 55% (43 to 65%) among adults 18-64 and from 40% (29 to 50%) to 55% (32 to 70%) among adults aged 65 and over. During a period of co-circulation of influenza A(H1N1)pdm09 and A(H3N2) in the United Kingdom, evidence for effectiveness of the influenza vaccine in both children and adults was found.

Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children

Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered ‘elite influenza controllers’.

Estimating averted illnesses from influenza vaccination for children and pregnant women – El Salvador, Panama, and Peru, 2011–2018

BackgroundEstimating the burden of disease averted by vaccination can assist policymakers to implement, adjust, and communicate the value of vaccination programs. Demonstrating the use of a newly available modeling tool, we estimated the burden of influenza illnesses averted by seasonal influenza vaccination in El Salvador, Panama, and Peru during 2011–2018 among two influenza vaccine target populations: children aged 6–23 months and pregnant women. MethodsWe derived model inputs, including incidence, vaccine coverage, vaccine effectiveness, and multipliers from publicly available country-level influenza surveillance data and cohort studies. We also estimated changes in illnesses averted when countries’ vaccine coverage was achieved using four different vaccine deployment strategies. ResultsAmong children aged 6–23 months, influenza vaccination averted an estimated cumulative 2,161 hospitalizations, 81,907 medically-attended illnesses, and 126,987 overall illnesses during the study period, with a prevented fraction ranging from 0.3 % to 12.5 %. Among pregnant women, influenza vaccination averted an estimated cumulative 173 hospitalizations, 6,122 medically attended illnesses, and 16,412 overall illnesses, with a prevented fraction ranging from 0.2 % to 10.9 %. Compared to an influenza vaccine campaign with equal vaccine distribution during March—June, scenarios in which total cumulative coverage was achieved in March and April consistently resulted in the greatest increase in averted illness (23 %-3,129 % increase among young children and 22 %-3,260 % increase among pregnant women). DiscussionInfluenza vaccination campaigns in El Salvador, Panama, and Peru conducted between 2011 and 2018 prevented hundreds to thousands of influenza-associated hospitalizations and illnesses in young children and pregnant women. Existing vaccination programs could prevent additional illnesses, using the same number of vaccines, by achieving the highest possible coverage within the first two months of an influenza vaccine campaign.

Hemagglutination Inhibition Antibody Titers as Mediators of Influenza Vaccine Efficacy Against Symptomatic Influenza A(H1N1), A(H3N2), and B/Victoria Virus Infections.

The hemagglutination inhibition antibody (HAI) titer contributes only a part of vaccine-induced protection against influenza virus infections. Using causal mediation analysis, we quantified the proportion of vaccine efficacy mediated by postvaccination HAI titers. We conducted causal mediation analyses using data from a randomized, active-comparator controlled, phase III, trial of an inactivated, split-virion seasonal quadrivalent influenza vaccine in children conducted from October 2010 to December 2011 in 8 countries. Vaccine efficacy was estimated using a weighted Cox proportional hazards model. Estimates were decomposed into the direct and indirect effects mediated by postvaccination HAI titers. The proportions of vaccine efficacy mediated by postvaccination HAI titers were estimated to be 22% (95% confidence interval, 18%--47%) for influenza A(H1N1), 20% (16%-39%) for influenza A(H3N2), and 37% (26%-85%) for influenza B/Victoria. HAI titers partially mediate influenza vaccine efficacy against influenza A(H1N1), A(H3N2), and B/Victoria. Our estimates were lower than in previous studies, possibly reflecting expected heterogeneity in antigenic similarity between vaccine and circulating viruses across seasons.