Immunogenicity and Safety of an Inactivated Quadrivalent Influenza Vaccine in US Children 6–35 Months of Age During 2013–2014: Results From A Phase II Randomized Trial

BACKGROUND: Viruses from 2 influenza B lineages co-circulate, leading to suboptimal protection with trivalent influenza vaccines (TIV). Quadrivalent influenza vaccines (QIV) containing both lineages offer broader protection. METHODS: We compared inactivated seasonal QIV versus TIV (15 and 7.5 μg hemagglutinin [HA] for each influenza strain, respectively) in a phase II randomized (1 : 1), observer-blind trial in US children 6–35 months of age (identifier NCT01974895). The primary objective was to evaluate immune responses induced by QIV for the 4 vaccine strains 28 days after completion of vaccination. A secondary objective was to demonstrate superiority of QIV versus TIV for the B/Victoria strain contained in QIV but not TIV. Immunogenicity was evaluated in the per-protocol cohort (N = 280), and safety was evaluated in the intent-to-treat cohort (N = 314). RESULTS: Seroconversion rates (SCRs) for QIV were 80.4% (95% confidence interval [CI], 73.0%–86.6%), 72.0% (95% CI, 63.9%–79.2%), 86.0% (95% CI, 79.2%–91.2%), and 66.4% (95% CI, 58.1%–74.1%) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria, respectively. Quadrivalent influenza vaccines demonstrated immunogenic superiority over TIV for B/Victoria with a geometric mean titer ratio of 4.73 (95% CI, 3.73%–5.99%) and SCR difference of 54.02% (95% CI, 43.88%–62.87%). Safety was similar between the vaccine groups despite the QIV's higher antigen content. No serious adverse events were reported related to vaccination. CONCLUSIONS: Quadrivalent influenza vaccine (15 µg HA/strain) was immunogenic with an acceptable safety profile. The next phase of its development in children 6–35 months of age is a phase III trial in countries where it is not yet licensed. In countries where it is already licensed, a switch from TIV to QIV would provide broader protection in this vulnerable group.