title: Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.
abstract: OBJECTIVE
  To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine.
  
  
  METHODS
  A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions.
  
  
  RESULTS
  In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group.
  
  
  CONCLUSIONS
  This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.
authors.affiliation: Department of Medicine, Saint Louis University, St Louis, Missouri, 63110, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Belshe
authors.forename: W C
authors.initials: WC
authors.lastname: Gruber
authors.forename: P M
authors.initials: PM
authors.lastname: Mendelman
authors.forename: I
authors.initials: I
authors.lastname: Cho
authors.forename: K
authors.initials: K
authors.lastname: Reisinger
authors.forename: S L
authors.initials: SL
authors.lastname: Block
authors.forename: J
authors.initials: J
authors.lastname: Wittes
authors.forename: D
authors.initials: D
authors.lastname: Iacuzio
authors.forename: P
authors.initials: P
authors.lastname: Piedra
authors.forename: J
authors.initials: J
authors.lastname: Treanor
authors.forename: J
authors.initials: J
authors.lastname: King
authors.forename: K
authors.initials: K
authors.lastname: Kotloff
authors.forename: D I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: F G
authors.initials: FG
authors.lastname: Hayden
authors.forename: K
authors.initials: K
authors.lastname: Zangwill
authors.forename: L
authors.initials: L
authors.lastname: Yan
authors.forename: M
authors.initials: M
authors.lastname: Wolff
mesh_terms: D000281:Administration, Intranasal; D002648:Child; D002675:Child, Preschool; D003080:Cold Temperature; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D011446:Prospective Studies; D014611:Vaccination; D014613:Vaccines, Attenuated
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated