Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study

Abstract

BackgroundVaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014–2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18years. MethodsParticipants (n=3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n=1741), IIV3-YAM (n=871), or IIV3-VIC (n=872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI]≤1.5) and seroconversion rate (SCR) difference (IIV3 – IIV4; upper bound of two-sided 95% CI≤10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7days postvaccination, AEs recorded for 28days postvaccination, and serious AEs for 6months postvaccination. ResultsIIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were −1.1 (−4.5, 2.3), −1.7 (−5.0, 1.7), −3.2 (IIV3-YAM; −7.4, 0.9), and −1.6 (IIV3-VIC; −5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%). ConclusionsIIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains not contained in IIV3 comparators. Safety/tolerability profiles were similar across vaccine groups.Funding: Seqirus; Clinicaltrials.gov: NCT02214225.