Safety and immunogenicity of unadjuvanted subvirion monovalent inactivated influenza H3N2 variant (H3N2v) vaccine in children and adolescents.

Abstract

OBJECTIVE\nIn response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children.\n\n\nSTUDY DESIGN\nThis multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21\u202fdays apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6-35\u202fmonths of age received 7.5mcg or 15mcg of hemagglutinin (HA)/dose; children 3-17\u202fyears 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\u202fdays after each vaccination; adverse events were assessed for 42\u202fdays and serious adverse events for 7\u202fmonths after the first vaccination. Immunogenicity was evaluated by measuring hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies to H3N2v prior to and 21\u202fdays after each vaccination. Cross-reactivity against seasonal H3N2 strains was evaluated.\n\n\nRESULTS\nThe 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\u202fmonths, and headache and fatigue in children 9-17\u202fyears old. Children 6-35\u202fmonths 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\u202fyears of age required two doses of vaccine to demonstrate a response, while 9-17\u202fyear olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 9-17\u202fyears of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses.\n\n\nCONCLUSION\nThe 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.