Immunogenicity and Reactogenicity of an Inactivated Quadrivalent Influenza Vaccine Administered Intramuscularly to Children 6 to 35 Months of Age in 2012–2013: A Randomized, Double-Blind, Controlled, Multicenter, Multicountry, Clinical Trial

Abstract

BackgroundInfluenza attack rates are high in 6- to 35-month-old children; vaccines containing both lineages of influenza B (Yamagata and Victoria), in addition to the H3N2 and H1N1 antigens, may improve protection rates.MethodsIn a randomized double-blind controlled trial, the immunogenicity and reactogenicity of an inactivated quadrivalent influenza vaccine (QIV) and a trivalent control vaccine (TIV) were assessed.ResultsSix hundred one children (QIV, n = 299; TIV, n = 302) were enrolled at 8 sites in 3 countries. The primary immunogenicity objective was met: the lower limit (LL) of the 2-sided 95% confidence interval (CI) for the seroconversion rate in QIV recipients ranged from 66.6% to 81.3%, which was ≥40% against all 4 strains. The immunogenic superiority of the additional B/Victoria strain in the QIV compared to that in the TIV was confirmed: the LL of the 2-sided 95% CI of the geometric mean titer ratio (QIV/TIV) (6.28 [95% CI, 5.32–7.41]) was greater than 1.5, and the LL of the 2-sided 95% CI for the difference in the seroconversion rate (QIV – TIV) (64.19% [95% CI, 57.65%–69.95%]) was greater than 10%. Injection-site pain and irritability/fussiness were the most commonly reported solicited injection-site and general adverse events, respectively, from days 0 to 6 and were similar in frequency between the groups.ConclusionsIn children aged 6 to 35 months, a QIV has superior immunogenicity for the added B strain and acceptable immunogenicity for shared strains, with no notable difference in reactogenicity and safety when compared to a TIV.

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

“…Some previous studies have suggested that pain at the injection site may be modestly increased with QIV compared with TIV or hepatitis A vaccine [25, 30], whereas others report similar levels of pain [21, 23, 26, 27]. The incidence of fever was similar with both vaccines, consistent with previous published studies [25, 30].…”

Evidence update: GlaxoSmithKline’s inactivated quadrivalent influenza vaccines

“…Injection site pain was modestly more common with Q-IIV4 (>30%) than D-IIV3 control (>20%) in children aged 3-17-years after the first dose. 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.…”

“…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).…”

“…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. Based on these results, a phase III randomized controlled study (NCT01711736; 2012-2013 [70]) was conducted in children aged The above clinical trials were performed with a preservative-free formulation of Q-IIV4 presented in pre-filled syringes. In order to offer a multidose vial presentation of Q-IIV4, a formulation in which thimerosal as a preservative was added as a terminal step, had to be tested for acceptable immunogenicity.…”

Fluarix quadrivalent vaccine for influenza

“…Interestingly, GSK has developed two quadrivalent influenza vaccines in parallel, Fluarix and Flulaval, for which immunogenicity data are similar [29][30][31][32], and one VE study using Flulaval was done which showed that the influenza vaccine was efficacious in preventing influenza in children, but failed to show a benefit of quadrivalent compared to trivalent vaccine [33].…”