Safety and Immunogenicity of Unadjuvanted Subvirion Monovalent Inactivated Influenza H3N2 Variant (H3N2v) Vaccine in Children and Adolescents

Publication Type
Journal Article
Year of Publication
2019
Authors
Munoz, Flor M; Anderson, Evan J; Bernstein, David I; Harrison, Christopher J; Pahud, Barbara; Anderson, Edwin; Creech, C Buddy; Berry, Andrea A; Kotloff, Karen L; Walter, Emmanuel B; Atmar, Robert L; Bellamy, Abbie R; Chang, Soju; Keitel, Wendy A
Secondary
Vaccine
Volume
37
Start Page
5161
Pagination
5161-5170
Date Published
08/2019
Keywords
Adolescents; children; Cross-reactive antibodies; H3N2 variant; Immunogenicity; influenza; safety
Abstract

OBJECTIVE: In response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children.

STUDY DESIGN: This multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21 days apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6-35 months of age received 7.5mcg or 15mcg of hemagglutinin (HA)/dose; children 3-17 years of age received 15mcg HA/dose. Safety and reactogenicity were assessed by measuring the occurrence of solicited injection site and systemic reactions in the 7 days after each vaccination; adverse events were assessed for 42 days and serious adverse events for 7 months after the first vaccination. Immunogenicity was evaluated by measuring hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies to H3N2v prior to and 21 days after each vaccination. Cross-reactivity against seasonal H3N2 strains was evaluated.

RESULTS: The H3N2v vaccine was well tolerated. Transient mild to moderate injection site tenderness, pain and erythema was observed, with the most commonly reported systemic reactogenicity being irritability in children 6-35 months, and headache and fatigue in children 9-17 years old. Children 6-35 months old, whether they received 7.5mcg or 15mcg/dose, had low HAI and Neut antibody responses after two doses compared to older children. Children under 9 years of age required two doses of vaccine to demonstrate a response, while 9-17 year olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 9-17 years of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses.

CONCLUSION: The H3N2v vaccine was safe and immunogenic in children and adolescents. Age-related increases in immunogenicity against H3N2v and seasonal H3N2 viruses were observed, suggesting prior priming via infection and/or immunization. Clinical trial registry: The trial is registered with clinicaltrial.gov: NCT02100436.