Immunogenicity of a Monovalent 2009 Influenza A(H1N1) Vaccine in Infants and Children

Abstract

HE DISEASE BURDEN OF SEAsonal influenza in the pediatric population is generally attributed to a combination of immunologic naivety, prolonged virus shedding, and enhanced transmission opportunity in child-care and educational institutions. 1 Consistent with this experience, initial reports of the introduction and indigenous transmission of 2009 influenza A(H1N1) infection in many countries have largely involved children, 2 often attending day or boarding schools. [3][4][5] Serosurveys have demonstrated little or no cross-reactivity of the pediatric sera sample to the new virus strain, under-Context In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children.Objective To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children.Design, Setting, and Participants Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia.Intervention Intramuscular injection of 15 µg or 30 µg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart.Main Outcome Measures Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination. ResultsFollowing the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-µg group (92.5%; 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-µg group (97.7%; 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI,). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity. ConclusionOne 15-µg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity. Trial Registration clinicaltrials.gov Identifier: NCT00940108

Safety and tolerability of a 2009 trivalent inactivated split‐virion influenza vaccine in infants, children and adolescents

“…19 From that same study, dose one values for the control split‐virion vaccine were consistently lower than any of the CSL preparations, including the one used in this study (Table 1). 19 Fever was also more common with the 30 μg (double) dose of CSL's 2009 monovalent influenza A(H1N1) vaccine: in an uncontrolled Australian study, for all participants (≥6 months to <9 years) following dose one any fever occurred in 24% (15 μg haemagglutinin) and 41% (30 μg) of recipients, and following dose two, 18% and 14%, respectively 24. From a placebo‐controlled US study using the same product, the proportion of participants with any fever in Cohort A (≥6 months to <3 years) following dose one or two was 23% (placebo arm), 25% (7·5 μg) and 43% (15 μg), for Cohort B (≥3 to <9 years) 14% (placebo), 19% (7·5 μg) and 20% (15 μg) 25…”

Absence of cross-reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months-9 years: a prospective study

“…Despite study commencement in May 2009, this protocol overlapped the recruitment phase for an urgent pandemic H1N1 vaccine trial, 15 making us ethically obliged to offer parents the choice of participation in one of two influenza vaccine studies. In consequence, only 20 children were enrolled – 3 in Cohort A and 17 in Cohort B.…”

Pre-pandemic and pandemic influenza vaccines

“…Protective immune responses could be achieved in children above 12 years of age. 82 In infants and children below 12 years, lower responses were observed that could be improved by a second dose of vaccine. [83][84][85] In contrast, in the Australian study, a single dose of vaccine was immunogenic in infants and children starting at 6 months of age.…”

“…[83][84][85] In contrast, in the Australian study, a single dose of vaccine was immunogenic in infants and children starting at 6 months of age. 82 These H1N1 trials demonstrated that an adjuvant was not required unlike the immune responses to H5N1 vaccine. While the discrepency between a single dose or two doses for inducing a sufficient immune response in infants and children is yet to be elucidated, the recommendation has been for two doses in children.…”