title: Efficacy and safety of 1 and 2 doses of live attenuated influenza vaccine in vaccine-naive children.
abstract: BACKGROUND
  We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine (LAIV) in influenza vaccine-naive children aged 6 to <36 months.
  
  
  METHODS
  Subjects were randomized to 1 of 4 regimens in year 1: 2 doses LAIV, 1 dose LAIV, excipient placebo, or saline placebo. In year 2, LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo. Because of an unintended treatment allocation error in year 2, 1 block of subjects who were randomized to LAIV received saline placebo and 1 block who were randomized to placebo received LAIV.
  
  
  RESULTS
  In year 1, vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was 73.5% and 57.7%, respectively, against antigenically similar strains. In year 2, absolute efficacy of a single dose of LAIV was 73.6% and 65.2%, respectively, in recipients of 2 and 1 doses of LAIV in year 1. Year 2 efficacy was 57.0% in subjects who received 2 doses of LAIV in year 1 and placebo in year 2. Safety and tolerability of LAIV were consistent with previous studies. Reactogenicity was similar between placebo groups. Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus placebo in years 1 and 2.
  
  
  CONCLUSIONS
  One dose of LAIV provided clinically significant protection against influenza in young children previously unvaccinated against influenza; 2 doses provided additional protection. Protection after 2 doses in year 1 persisted through a second season without revaccination. LAIV excipients were not a major contributor to reactogenicity. These benefits provide support for increased use of LAIV in children > or =2 years of age.
authors.affiliation: Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Humberto
authors.initials: H
authors.lastname: Bracco Neto
authors.forename: Calil K
authors.initials: CK
authors.lastname: Farhat
authors.forename: Miguel Wenceslao
authors.initials: MW
authors.lastname: Tregnaghi
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Ahmad
authors.initials: A
authors.lastname: Razmpour
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palladino
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Small
authors.forename: William C
authors.initials: WC
authors.lastname: Gruber
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Forrest
mesh_terms: D000281:Administration, Intranasal; D001118:Argentina / Q000453:epidemiology; D001938:Brazil / Q000453:epidemiology; D002675:Child, Preschool; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; 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 / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007251:Influenza, Human / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D015337:Multicenter Studies as Topic; D010033:Otitis Media / Q000150:complications; D013019:South Africa / Q000453:epidemiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D014613:Vaccines, Attenuated