title: 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: 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 ≥18years.
  
  
  
  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 7days postvaccination, AEs recorded for 28days postvaccination, and serious AEs for 6months postvaccination.
  
  
  
  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%).
  
  
  
  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.
  
  
  
  Seqirus; Clinicaltrials.gov: NCT02214225.
authors.affiliation: University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, United States.
authors.forename: John T
authors.initials: JT
authors.lastname: Treanor
authors.affiliation: Clinical Development, Seqirus Pty Ltd, Parkville, Victoria, Australia. Electronic address: frank.albano@seqirus.com.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Albano
authors.affiliation: Pharmacovigilance and Risk Management, Seqirus Pty Ltd, Parkville, Victoria, Australia.
authors.forename: Daphne C
authors.initials: DC
authors.lastname: Sawlwin
authors.affiliation: Pharmacovigilance and Risk Management, Seqirus Pty Ltd, Parkville, Victoria, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Graves Jones
authors.affiliation: Clinical Development, Seqirus Pty Ltd, Parkville, Victoria, Australia.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Airey
authors.affiliation: Clinical Development, Seqirus Pty Ltd, Parkville, Victoria, Australia.
authors.forename: Neil
authors.initials: N
authors.lastname: Formica
authors.affiliation: Clinical Development, Seqirus Pty Ltd, Parkville, Victoria, Australia.
authors.forename: Vince
authors.initials: V
authors.lastname: Matassa
authors.affiliation: Medical Affairs, Seqirus Pty Ltd, Parkville, Victoria, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Leong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014481:United States; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Immunogenicity; Inactivated; Influenza vaccine; Noninferiority; Quadrivalent; Safety