title: A randomized, double-blind noninferiority study of quadrivalent live attenuated influenza vaccine in adults.
abstract: BACKGROUND
  Trivalent seasonal influenza vaccines contain 2 A strains and 1 B strain. B strains of 2 antigenically distinct lineages, Yamagata and Victoria, have been co-circulating annually, and the B strain included in vaccines often has not been a lineage match to the major circulating strain. Thus, a vaccine containing B strains from both lineages could broaden protection against influenza. Quadrivalent live attenuated influenza vaccine (Q/LAIV) is an investigational 4-strain formulation of LAIV that contains 2 A strains, A/H1N1 and A/H3N2, and 2 B strains, 1 from each lineage.
  
  
  METHODS
  A randomized, double-blind, active-controlled study of Q/LAIV was conducted in 1800 adults aged 18-49 years to compare the immunogenicity and safety of Q/LAIV to trivalent LAIV (T/LAIV). Subjects were randomized 4:1:1 to receive an intranasal dose of Q/LAIV (n=1200) or 1 of 2 matching T/LAIV vaccines, each containing 1 of the B strains included in Q/LAIV (n=600 total). The primary endpoint was the comparison of the post-vaccination strain-specific geometric mean titers (GMT) of hemagglutination inhibition antibody in Q/LAIV recipients to those in T/LAIV recipients, with immunologic noninferiority of Q/LAIV to be demonstrated if the upper bound of the 2-sided 95% confidence interval (CI) for the ratio of the GMTs [T/LAIV divided by Q/LAIV] was ≤1.5 for all strains.
  
  
  CONCLUSIONS
  Q/LAIV met the criteria for noninferiority: the ratios of the GMTs for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.09 (95% CI, 1.01-1.18), 1.05 (95% CI, 0.96-1.14), 1.10 (95% CI, 0.97-1.25), and 0.92 (95% CI, 0.82-1.03), respectively. Solicited symptoms and adverse events were similar in the Q/LAIV and T/LAIV arms. Q/LAIV may confer increased protection against influenza by targeting B strains from both lineages.
authors: Kentucky Pediatric and Adult Research, 201 South 5th Street, Bardstown, KY 40004-1142, USA. slblock@pol.net
authors: Stan L
authors: SL
authors: Block
authors: Tingting
authors: T
authors: Yi
authors: Eric
authors: E
authors: Sheldon
authors: Filip
authors: F
authors: Dubovsky
authors: Judith
authors: J
authors: Falloon
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D004311:Double-Blind Method; D023381:Endpoint Determination; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008875:Middle Aged; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated