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

Abstract

BackgroundViruses 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.MethodsWe 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).ResultsSeroconversion 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.ConclusionsQuadrivalent 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.

Prevention and Control of Seasonal Influenza with Vaccines

“…Most local and general adverse events are temporary and mild to moderate in severity. Among children, the most common safety complaint was a modest increase in injection-site pain (124,126,128,300). The first postlicensure review of VAERS reports covering the 2013-14 and 2014-15 seasons noted that the most common adverse events reported following receipt of IIV4 among children aged 6 months through 17 years were injection-site reactions and fever.…”

Evidence update: GlaxoSmithKline’s inactivated quadrivalent influenza vaccines

“…In the two randomized controlled phase II studies of Q-IIV4 in children aged 6-35 months, [69,70] the frequencies of both injection site and systemic AEs including fever, notable for its link with febrile seizures, following vaccination were comparable in the Q-IIV4 and IIV3 recipients, after dose 1 or 2, and across the age strata (6−17 months and 18 −35 months of age). [71] In all studies, [57,[67][68][69][70][71] regardless of age group, the rates of unsolicited AEs over 21 −28 days after vaccination and of medically attended and SAE during the entire clinical trials were comparable between Q-IIV4 and control groups. These outcomes provided assurance that Q-IIV4 posed no incremental safety risk relative to IIV3s.…”

“…There have been two additional controlled trials of Q-IIV4 in children aged 6−35 months to support its eventual licensure in this group beyond Canada and Mexico. Overall, immunogenicity data are available for adults aged ≥18 years, [67,68] children aged 3-17 years, [69] and children aged 6-35 months [69][70][71] (Supplementary File 3).…”

“…[67] In a phase III trial (NCT01198756; 2010-2011 [69]) conducted in children in stable health aged [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] In an open-label arm of the study conducted in children aged 6-35 months (N = 301), Q-IIV4 was less immunogenic than in children aged 3-17 years, but nevertheless met CBER immunogenicity acceptance criteria. [69] A phase II randomized controlled study (NCT01974895; 2013-2014 [71]) of Q-IIV4 was conducted in US children aged 6-35 months (N = 314) using the only US-licensed IIV3 for this age group as control vaccine. [71] Q-IIV4 was shown to be immunogenic with SCRs of 80.4%, 72.0%, 86.0%, and 66.4% against the A/H1N1, A/H3N2, B/Yamagata, and B/ Victoria strains, respectively; these results met CBER SCR licensure criteria.…”

“…[69] A phase II randomized controlled study (NCT01974895; 2013-2014 [71]) of Q-IIV4 was conducted in US children aged 6-35 months (N = 314) using the only US-licensed IIV3 for this age group as control vaccine. [71] Q-IIV4 was shown to be immunogenic with SCRs of 80.4%, 72.0%, 86.0%, and 66.4% against the A/H1N1, A/H3N2, B/Yamagata, and B/ Victoria strains, respectively; these results met CBER SCR licensure criteria. Notably, Q-IIV4 had similar immunogenicity for the shared vaccine strains relative to the IIV3, formulated with a B/Yamagata strain, and superior immunogenicity for the additional B/Victoria strain.…”