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

Background. Influenza 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. Methods. In 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. Results. Six 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. Conclusions. In 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.