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. Issue 15 (4th April 2017)

• Record Type: Journal Article
• Authors: Treanor, John T.; Albano, Frank R.; Sawlwin, Daphne C.; Graves Jones, Alison; Airey, Jolanta; Formica, Neil; Matassa, Vince; Leong, Jane
• Is Part Of: Vaccine. Volume 35:Issue 15(2017)
• Page Start: 1856
• Page End: 1864
• Publication Date: 2017-04-04
• Subjects: Immunogenicity -- Inactivated -- Influenza vaccine -- Noninferiority -- Quadrivalent -- Safety; AE adverse event -- CI confidence interval -- DSMB Data and Safety Monitoring Board -- FAS full analysis set -- GMFI geometric mean fold increase -- GMT geometric mean titer -- HI hemagglutination inhibition -- IIV3 trivalent inactivated influenza vaccine -- IIV4 quadrivalent inactivated influenza vaccine -- LS least square -- SAE serious adverse event -- SCR seroconversion rate -- SD standard deviation -- SPR seroprotection rate -- US United States -- VIC Victoria -- YAM Yamagata; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.02.066
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Seqirus IIV4 was compared to two IIV3 comparators with alternate B lineage strains. Seqirus IIV4 was immunologically noninferior to both IIV3 comparators. The immunogenicity of IIV4 was superior for the IIV3 unmatched B strain. IIV4 was well tolerated, with a similar safety profile to IIV3 comparators. Abstract: Background: Vaccination 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 ≥18 years. Methods: Participants (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 7 days postvaccination, AEs recorded for 28 days postvaccination, and serious AEs for 6 months postvaccination. Results: IIV4 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%). Conclusions: IIV4 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 .