title: Relative efficacy of AS03-adjuvanted pandemic influenza A(H1N1) vaccine in children: results of a controlled, randomized efficacy trial.
abstract: BACKGROUND
  The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010-2011.
  
  
  METHODS
  A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed.
  
  
  RESULTS
  There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%-93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group.
  
  
  CONCLUSIONS
  The 4-8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661.
authors.affiliation: Murdoch Children's Research Institute Melbourne School of Population and Global Health, University of Melbourne, Carlton, Australia.
authors.forename: Terry
authors.initials: T
authors.lastname: Nolan
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.
authors.forename: Sumita
authors.initials: S
authors.lastname: Roy-Ghanta
authors.affiliation: Department of Pediatrics, Mary Chiles General Hospital, Manila.
authors.forename: May
authors.initials: M
authors.lastname: Montellano
authors.affiliation: Pediatric Infectious Diseases, Department of Pediatrics, Universidade Federal de São Paulo.
authors.forename: Lily
authors.initials: L
authors.lastname: Weckx
authors.affiliation: Instituto Costarricense de Investigaciones Clínicas, San José, Costa Rica.
authors.forename: Rolando
authors.initials: R
authors.lastname: Ulloa-Gutierrez
authors.affiliation: National Institute of Public Health of Mexico, Cuernavaca Morelos.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lazcano-Ponce
authors.affiliation: Infectious Diseases Unit, Department of Pediatrics, Phramongkutklao Hospital, Bangkok.
authors.forename: Angkool
authors.initials: A
authors.lastname: Kerdpanich
authors.affiliation: Department of Pediatrics, Faculdade de Ciências Médicas da Santa Casa de São Paulo Associação Fundo de Incentivo à Pesquisa, São Paulo, Brazil.
authors.forename: Marco Aurélio Palazzi
authors.initials: MA
authors.lastname: Safadi
authors.affiliation: National Institute of Public Health of Mexico, Cuernavaca Morelos.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cruz-Valdez
authors.affiliation: Department of Pediatrics, De La Salle Health Sciences Institute, Dasmariñas City.
authors.forename: Sandra
authors.initials: S
authors.lastname: Litao
authors.affiliation: National Healthcare Group Polyclinics, Singapore.
authors.forename: Fong Seng
authors.initials: FS
authors.lastname: Lim
authors.affiliation: Servicios Medicos Universidad Autonoma de Nuevo Leon, Monterrey.
authors.forename: Abiel Mascareñas
authors.initials: AM
authors.lastname: de Los Santos
authors.affiliation: Instituto Nacional de Pediatría de Mexico, Ciudad e Mexico.
authors.forename: Miguel Angel Rodriguez
authors.initials: MA
authors.lastname: Weber
authors.affiliation: Hospital General de Durango, Durango, Mexico.
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Tinoco
authors.affiliation: Instituto Costarricense de Investigaciones Clínicas, San José, Costa Rica.
authors.forename: Marcela Hernandez-de
authors.initials: MH
authors.lastname: Mezerville
authors.affiliation: Instituto Costarricense de Investigaciones Clínicas, San José, Costa Rica.
authors.forename: Idis
authors.initials: I
authors.lastname: Faingezicht
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Pensri
authors.initials: P
authors.lastname: Kosuwon
authors.affiliation: Centro de Estudios en Infectologia Pediatrica, Cali, Colombia.
authors.forename: Pio
authors.initials: P
authors.lastname: Lopez
authors.affiliation: Department of Health, Research Institute for Tropical Medicine, Muntinlupa, Philippines.
authors.forename: Charissa
authors.initials: C
authors.lastname: Borja-Tabora
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: GlaxoSmithKline Vaccines, Wavre.
authors.forename: Serge
authors.initials: S
authors.lastname: Durviaux
authors.affiliation: Novavax, Rockville, Maryland.
authors.forename: Louis
authors.initials: L
authors.lastname: Fries
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
authors.affiliation: GlaxoSmithKline Vaccines, Wavre.
authors.forename: Thomas
authors.initials: T
authors.lastname: Breuer
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D011446:Prospective Studies; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: H1N1; children; efficacy; influenza virus; pandemic influenza vaccine