Influenza Vaccine In Young Children Research Articles

Optimal timing of influenza vaccination in young children: population based cohort study

ObjectiveTo assess optimal timing of influenza vaccination in young children.DesignPopulation based cohort study.SettingUnited States.ParticipantsCommercially insured children aged 2-5 years who were vaccinated against influenza during 2011-18.Main outcome measureRates of diagnosis...

Quadrivalent influenza vaccine (Sinovac Biotech) for seasonal influenza prophylaxis

ABSTRACT Introduction Quadrivalent Influenza Vaccine (Sinovac Biotech) is a quadrivalent split-virion-inactivated influenza vaccine approved in China in June 2020 for individuals ≥3 years of age. It contains 15 µg hemagglutinin per strain including A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, which could potentially improve protection against influenza B viruses. Areas covered In this review, we summarize the development of quadrivalent influenza vaccines in China and foreign countries, and assess the immunogenicity and safety from the phase I and III clinical trials of Quadrivalent Influenza Vaccine in individuals ≥3 years of age. We also discuss the potential application of Quadrivalent Influenza Vaccine in young children 6–35 months of age according to the results of the phase III trial. Expert commentary The immunogenicity and safety profiles of Quadrivalent Influenza Vaccine containing two A and two B strains were comparable to the trivalent vaccines for the shared strains. The addition of a second B strain to the trivalent vaccine could induce superior immune responses for the alternate B strain. Since the two B strains co-circulated worldwide, the introduction of quadrivalent influenza vaccines has been expected to be a cost-effective strategy.

Knowledge, beliefs and attitudes of general practitioners and general practice nurses regarding influenza vaccination for young children.

Annual vaccination is effective in reducing the harms associated with seasonal influenza. However, the uptake of influenza vaccine has historically been low in children. This paper reports a descriptive survey that sought to explore the beliefs, attitudes, and knowledge of general practitioners (GPs) and general practice nurses (GPNs) towards influenza vaccination in young children. Both GPs and GPNs working in the Illawarra Shoalhaven Local Health District (ISLHD) in NSW, Australia, were invited via email, fax and social media to participate in the study. A total of 121 participants completed the survey. Most participants had a high level of support and knowledge of influenza immunisation in young children. Barriers to influenza immunisation in young children included perceived hesitancy in parents and competing clinical demands. The participants strongly supported funding of the vaccine, with 90.9% feeling that parents would be less likely to vaccinate their children if the vaccine were no longer free. Both GPs and GPNs differed in the use of influenza vaccination resources. The participants had a positive attitude to influenza immunisation in young children and strongly supported continued funding of the vaccine. Dedicated young children's influenza vaccination clinics run by general practices or in the community could reduce the impact of competing clinical demands.

Influenza-Associated Medical Visits Prevented by Influenza Vaccination in Young Children in Thailand, 2012-2014.

Despite recommendations, few children aged 6-35 months in Thailand receive seasonal influenza vaccination. Using previously estimated incidence and vaccine effectiveness data from the period 2012-2014, we estimate that up to 121 000 medical visits could be prevented each year with 50% coverage and expanded recommendations to children aged <5 years.

The Clinical Importance of a Second Dose of Influenza Vaccination in Young Children

The Clinical Importance of a Second Dose of Influenza Vaccination in Young Children

Timeliness of signal detection for adverse events following influenza vaccination in young children: a simulation case study

ObjectivesTo determine how soon after commencement of the seasonal influenza vaccination programme, the AusVaxSafety active vaccine safety surveillance system, currently in use across Australia, would have detected a safety signal...

Cumulative clinical experience with MF59-adjuvanted trivalent seasonal influenza vaccine in young children

ObjectiveTo demonstrate the potential of an MF59-adjuvanted inactivated trivalent seasonal influenza vaccine (aIIV3; Fluad™) to improve the immune response in young children, we review the immunogenicity, efficacy, and safety/tolerability of aIIV3 from a comprehensive clinical development program in a pediatric population with a specific need for improved influenza vaccines. MethodsData were analyzed from a series of 1 phase Ib, 3 phase II, and 2 phase III studies involving 11,942 children aged 6 months through 5years. ResultsThe clinical data showed that aIIV3 had statistically significantly greater immunogenicity and efficacy in the prevention of influenza compared to conventional inactivated trivalent seasonal influenza vaccines (IIV3s). The safety profile of aIIV3 was generally similar to that of nonadjuvanted IIV3, apart from an increased frequency of solicited adverse events (AEs) following vaccination. The majority of solicited AEs were mild or moderate in severity and resolved within 1 to 3 days. ConclusionsaIIV3 was well tolerated, with immunogenicity and efficacy exceeding that of conventional IIV3 in children 6 months through 5years of age. The MF59-adjuvanted vaccine has the potential to fulfill an unmet clinical need in the prevention of seasonal influenza in this age group.

Modification of the vaccine manufacturing process improves the pyrogenicity profile of inactivated influenza vaccines in young children

BackgroundThere were increased reports of fevers and febrile reactions in young children (particularly children aged <5 years) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively. MethodsFor each study, fever rates (any grade and severe) were determined for the following age subgroups (as applicable), using the fever intensity grading system used in the S-IIV3/S-IIV4 studies: 6 months to <3 years; 3 to <5 years; 5 to <9 years; and 9 to <18 years. ResultsFor each age subgroup, the any grade and severe fever rates were lower in the S-IIV3/S-IIV4 studies than in the historical IIV3 formulation studies, with the greatest differences in fever rates observed in the youngest age groups. In the 6 months to <3 years group, the any grade fever rate was 7.0% (severe fever: 2.5%) in one S-IIV4 study compared with 38.7% to 40.0% (severe fever: 9.6% to 17.8%) in the historical IIV3 formulation studies. In the 3 to <5 years subgroup, the any grade fever rate was 4.9% (severe fever: 1.2%) in one S-IIV4 study compared with 34.1% to 36.0% (severe fever: 6.3% to 16.5%) in the historical IIV3 formulation studies. ConclusionThis analysis provides clinical evidence that the modified manufacturing process improved the fever profile across all pediatric age groups, in particular, in children aged <5 years.

Cumulative clinical experience with MF59-adjuvanted trivalent seasonal influenza vaccine in young children and adults 65 years of age and older

ObjectiveTo assess the long-term safety of MF59-adjuvanted trivalent influenza vaccine (aIIV3; Fluad™) in adults ≥65 years of age. MethodsData from 36 primary vaccination and 7 re-vaccination Phase I through III trials were analyzed; 7532 subjects received aIIV3 and 5198 subjects a nonadjuvanted trivalent inactivated influenza vaccine (IIV3). These trials were evaluated in 2 data poolings: first-dose randomized controlled trials (FD-RCT) and revaccination trials. Spontaneously reported adverse events (AEs) from post-marketing surveillance were also analyzed. ResultsThe percentages of subjects reporting AEs following vaccination were similar between aIIV3 and IIV3: 24.8% for aIIV3 vs 26.7% for IIV3 (relative risk [RR] 0.94; 95% confidence interval [CI] 0.87–1.01). The percentage of subjects with serious AEs was 6.7% for aIIV3 vs 7.0% for IIV3 (RR 0.95; 95% CI 0.82–1.09). Percentages of subjects with AEs leading to withdrawal, hospitalizations, adverse events of special interest (AESIs), and deaths between vaccination groups were similar. There was no signal of disproportionality for AESIs associated with aIIV3 compared to IIV3 in the post-marketing database. ConclusionsThis integrated safety analysis demonstrates an acceptable safety profile for aIIV3 in adults ≥65 years of age.

Efficacy of inactivated influenza vaccines in young children

Efficacy of inactivated influenza vaccines in young children

The effect of antipyretics on immune response and fever following receipt of inactivated influenza vaccine in young children.

Antipyretics reduce fever following childhood vaccinations; after inactivated influenza vaccine (IIV) they might ameliorate fever and thereby decrease febrile seizure risk, but also possibly blunt the immune response. We assessed the effect of antipyretics on immune responses and fever following IIV in children ages 6 through 47 months. Over the course of three seasons, one hundred forty-two children, receiving either a single or the first of 2 recommended doses of IIV, were randomized to receive either oral acetaminophen suspension (n = 59) or placebo (n = 59) (double-blinded) or ibuprofen (n = 24) (open-label) immediately following IIV and every 4-8 h thereafter for 24 h. Blood samples were obtained at enrollment and 4 weeks following the last recommended IIV dose. Responses to IIV were assessed by hemagglutination inhibition assay (HAI). Seroprotection was defined as an HAI titer ≥1:40 and seroconversion as a titer ≥1:40 if baseline titer <1:10 or four-fold rise if baseline titer ≥1:10. Participants were monitored for fever and other solicited symptoms on the day of and day following IIV. Significant differences in seroconversion and post-vaccination seroprotection were not observed between children included in the different antipyretic groups and the placebo group for the vaccine antigens included in IIV over the course of the studies. Frequencies of solicited symptoms, including fever, were similar between treatment groups and the placebo group. Significant blunting of the immune response was not observed when antipyretics were administered to young children receiving IIV. Studies with larger sample sizes are needed to definitively establish the effect of antipyretics on IIV immunogenicity.

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

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

Use of live attenuated influenza vaccines in young children in resource-poor settings.

Use of live attenuated influenza vaccines in young children in resource-poor settings.

Reactogenicity of trivalent inactivated influenza vaccine in young children: Pronounced reactions by previous successive vaccinations

In order to assess factors associated with reactogenicity of trivalent inactivated influenza vaccine (IIV3) among young children, data on 1538 vaccinees aged 0–5 years in a previous vaccine effectiveness study were analyzed.The most frequent reaction was redness (19%), followed by induration, swelling, itching, and pain (6–12%); there were no serious adverse events. For some local reactions, multivariate analyses indicated associations of younger age, preschool attendance, presence of siblings, and allergy with lower risk, and use of thinner needles with higher risk. Most notably, administration of one or more IIV3 vaccines during the previous 3 seasons was positively associated with each local reaction (adjusted odds ratios: 3.6–5.4). For subjects aged ≥3 years, prior successive annual vaccinations were associated with substantially increased local reactions, with clear dose-response relationships (P for trend: <0.001 for each); for example, an 9.8-fold greater risk of swelling following three successive annual vaccinations before the study season.

Immunogenicity and tolerability of an MF59-adjuvanted, egg-derived, A/H1N1 pandemic influenza vaccine in children 6-35 months of age.

Vaccines against pandemic A/H1N1 influenza should provide protective immunity in children, because they are at greater risk of disease than adults. This study was conducted to identify the optimal dose of an MF59®-adjuvanted, egg-derived, A/H1N1 influenza vaccine for young children. Children 6-11 months (N = 144) and 12-35 months (N = 186) of age received vaccine formulations containing either 3.75 μg antigen with half the standard dose of MF59 or 7.5 μg antigen with a standard dose of MF59, or a nonadjuvanted formulation containing 15 μg antigen (children 12-35 months only). Participants were given 2 primary vaccine doses 3 weeks apart, followed by 1 booster dose of MF59-adjuvanted seasonal influenza vaccine 1 year later. Immunogenicity was assessed by hemagglutination inhibition and microneutralization assays. All vaccine formulations were highly immunogenic and met all 3 European licensure criteria after 2 doses. MF59-adjuvanted vaccines met all licensure criteria after 1 dose in both age cohorts, while nonadjuvanted vaccine did not meet all criteria after 1 dose in children 12-35 months. A single booster dose was highly immunogenic, and stable antibody persistence was observed in response to all vaccines. All vaccines were well tolerated. In this study, a single dose of 3.75 μg antigen with half the standard dose of MF59 was shown to be optimal, providing adequate levels of immediate and long-term antibodies in pediatric subjects 6-35 months of age. These data demonstrated that MF59 adjuvant allowed for reduced antigen content and promoted significant long-term antibody persistence in children, with a satisfactory safety profile.

Safety and immunogenicity profiles of an adjuvanted seasonal influenza vaccine in Guatemalan children

The efficacy of non-adjuvanted seasonal influenza vaccine in young children is considered to be suboptimal. This study compared the safety and immunogenicity profiles of MF59-adjuvanted, trivalent, influenza vaccine (ATIV) and non-adjuvanted, trivalent, influenza vaccine (TIV) in Guatemalan children (N = 360) between 6 and < 60 months of age. Children received two doses of ATIV or TIV administered four weeks apart. Solicited adverse reactions were recorded for seven days after each vaccination. Serious adverse events were recorded throughout the entire study period. Antibody responses were assessed by hemagglutination inhibition (HI) assay at baseline, four weeks after administration of the first vaccine dose, and three weeks after administration of the second dose. Both ATIV and TIV were well tolerated, with similar rates of solicited reactions and adverse events observed in response to both vaccines. MF59-adjuvanted vaccine induced considerably higher antibody titers than did TIV. After two doses, the B strain-specific antibody response to TIV was insufficient to meet the Center for Biologics Evaluation and Research (CBER) licensure criterion for seroprotection, whereas responses to the MF59-adjuvanted vaccine met the seroprotection criterion against all three strains. Cross-reactive antibody responses to MF59-adjuvanted vaccine met the CBER seroprotection criterion against all three strains after two doses; B strain-specific heterologous responses to non-adjuvanted TIV were inadequate. The MF59-adjuvanted seasonal influenza vaccine was well-tolerated and highly immunogenic in children 6 to < 60 months of age, inducing seroprotective antibody titers against both the vaccine strains and antigenically distinct heterologous strains.

Adjuvanted versus nonadjuvanted influenza vaccines in young children: comparing results from recent clinical trials

A relatively high burden of influenza is experienced by young children. In order to successfully tackle the burden of influenza in children, effective vaccines are necessary. Accumulated evidence on the efficacy and effectiveness of traditional inactivated split or subunit trivalent influenza vaccines points towards no significant protection in the youngest children, who are largely unprimed. Adjuvanted influenza vaccines have been developed to improve the immune response, and could possibly overcome limitations of traditional influenza vaccines in the youngest age groups. In this review, evidence from recent clinical trials of adjuvanted versus nonadjuvanted influenza vaccines in children younger than 3 years of age will be discussed. Important findings from identified studies will be highlighted, and ongoing challenges concerning the use of adjuvanted influenza vaccine in young children will be discussed.

More on influenza vaccine in young children.

n engl j med 366;26 nejm.org june 28, 2012 2528 formed of the available treatments for multiple sclerosis. They were also reminded of the available treatments and of their right to leave the study during the trial if a relapse or progression of their disability was diagnosed, and they were required to sign a second consent form at this time. Because we instituted these measures, which were reviewed and approved by every ethics committee and competent health authority involved in the study, we are confident that patients were fully aware of the currently available treatment options. Furthermore, it should be considered that many patients were needle-phobic and tended to reject injection therapies, which were the only first-line therapies available at the time the study began. Approximately 38% of the patients in the laquinimod group and 40% of those in the placebo group had received treatments for multiple sclerosis before the study began, and these patients consented to participation.

The safety and efficacy of live attenuated influenza vaccine in young children with asthma or prior wheezing

In the European Union and Canada, an Ann Arbor strain live attenuated influenza vaccine (LAIV) is approved for use in children aged 2–17 years, including those with mild to moderate asthma or prior wheezing. The safety and efficacy of LAIV versus trivalent inactivated influenza vaccine (TIV) in children with asthma aged 6–17 years have been demonstrated. However, few data are available for children younger than 6 years of age with asthma or prior wheezing. Safety and efficacy data were collected for children aged 2–5 years with asthma or prior wheezing from two randomized, multinational trials of LAIV and TIV (N = 1,940). Wheezing, lower respiratory illness, and hospitalization were not significantly increased among children receiving LAIV compared with TIV. Increased upper respiratory symptoms and irritability were observed among LAIV recipients (p < 0.05). Relative efficacies were consistent with the results observed in the overall study populations, which demonstrated fewer cases of culture-confirmed influenza illness in LAIV compared with TIV recipients. Study results support the safety and efficacy of LAIV among children aged 2–17 years with mild to moderate asthma or a history of wheezing. Data regarding LAIV use are limited among individuals with severe asthma or active wheezing within the 7 days before vaccination.

Immunogenicity and Safety of 2 Dose Levels of a Thimerosal-Free Trivalent Seasonal Influenza Vaccine in Children Aged 6-35 Months: A Randomized, Controlled Trial.

Background.Improved influenza vaccine strategies for infants and preschool children are a high priority.Methods.The immunological response and safety of a thimerosal-free trivalent inactivated influenza vaccine at 2 different doses (0.50 mL vs 0.25 mL) was evaluated in children aged 6–35 months. The study was randomized, observer blind, multicenter, and stratified by age (6–23 months and 24–35 months), and it accounted for prior influenza immunization status.Results.Three hundred seventy-four children were in the total vaccinated cohort (study vaccine 0.25-mL dose, n = 164; 0.50-mL dose, n = 167; comparator 0.25 mL, n = 43). Regulatory criteria for immunogenicity of influenza vaccines in adults were met for all virus strains and doses for both age strata. A modest but not statistically significant improvement in immune responses was observed with the higher dose and reactogenicity, and safety of the 2 doses was not significantly different.Conclusions.The 0.5-mL dose of the study vaccine, when administered to children aged 6–35 months, resulted in a modest but not statistically significant improvement in immunogenicity with clinically similar safety and reactogenicity compared with the 0.25-mL dose. Further studies comparing full- and half-dose influenza vaccine in young children are needed.Clinical Trials Registration.NCT00778895.