title: Immunogenicity and safety of a quadrivalent live attenuated influenza vaccine in children.
abstract: BACKGROUND
  Influenza B viruses from 2 lineages cocirculate annually. Because the single B strain contained in trivalent vaccines may not match the major circulating strain, adding a second B virus could enhance protection. This study compared the safety and immunogenicity of an investigational quadrivalent Ann Arbor strain live attenuated influenza vaccine (Q/LAIV) with that of 2 trivalent vaccines (T/LAIV), each containing a B strain from a different lineage.
  
  
  METHODS
  This randomized, double-blind study was designed to demonstrate the immunologic noninferiority of Q/LAIV compared with T/LAIV in children 2-17 years of age by comparing postdose geometric mean titers of hemagglutination inhibition antibodies. Children were randomized 3:1:1 to receive Q/LAIV or 1 of 2 T/LAIV vaccines. Those subjects who were 9-17 years of age received 1 dose, and those 2-8 years of age received 2 doses 1 month apart. Serum immune responses were evaluated 1 month after dose 1 (dose 2 for influenza vaccine-naive subjects aged 2-8 years).
  
  
  RESULTS
  Q/LAIV was noninferior to T/LAIV: upper bounds for all four 95% confidence intervals for the postdose geometric mean titer ratios (T/LAIV divided by Q/LAIV) were ≤1.5, the predefined noninferiority margin. The overall seroresponse rates (4-fold rise) were comparable between treatment groups. Safety events were comparable, except that fever was more common after dose 1 in Q/LAIV subjects (5.1%) than in T/LAIV subjects (3.1%) 2-8 years of age.
  
  
  CONCLUSIONS
  The immunogenicity of Q/LAIV was noninferior to that of T/LAIV in children aged 2-17 years; safety was also comparable. Q/LAIV may broaden the protection against influenza B strains provided by current trivalent influenza vaccines.
authors.affiliation: Kentucky Pediatric and Adult Research, Bardstown, KY, USA.
authors.forename: Stan L
authors.initials: SL
authors.lastname: Block
authors.forename: Judith
authors.initials: J
authors.lastname: Falloon
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hirschfield
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Krilov
authors.forename: Filip
authors.initials: F
authors.lastname: Dubovsky
authors.forename: Tingting
authors.initials: T
authors.lastname: Yi
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated