title: Enhanced and persistent antibody response against homologous and heterologous strains elicited by a MF59-adjuvanted influenza vaccine in infants and young children.
abstract: BACKGROUND
  Non-adjuvanted seasonal influenza vaccines show only modest efficacy in young children. This study compared the immunogenicity, reactogenicity and safety of the MF59-adjuvanted trivalent subunit vaccine (aTIV) with two non-adjuvanted trivalent vaccines, TIV-1, the non-adjuvanted version of aTIV, and TIV-2, a split virion vaccine.
  
  
  METHODS
  6078 children received two doses of aTIV (n=3125), TIV-1 (n=1479), or TIV-2 (n=1474) four weeks apart (Days 1 and 29). Children aged 6 to <36 months and 36 to <72 months received 0.25 mL and 0.50 mL doses, respectively. Immunogenicity was assessed by hemagglutination inhibition (HI) assay (n=2435) on Days 1, 29, 50 and 209. Safety was assessed up to Day 394.
  
  
  RESULTS
  After the second vaccination (Day 50), the aTIV group showed significantly higher geometric mean HI titers and seroconversion rates than the TIV-1 or TIV-2 groups against all homologous and heterologous strains. The difference was enhanced at HI titers ≥110. aTIV elicited a faster, more persistent antibody response, with significantly higher titers in the aTIV group after one vaccination (Day 29) and after six months (Day 209) than in either TIV group. aTIV was more reactogenic than were TIV-1 and TIV-2 but rates of severe adverse events were very low for all three vaccines.
  
  
  CONCLUSIONS
  In infants and young children, the MF59-adjuvanted vaccine induced substantially faster (after one dose), higher, persistent HI titers than the non-adjuvanted vaccines, with consistently higher seroprotection rates at increased threshold HI titers. This trial is registered at clinicaltrials.gov: NCT01346592.
authors.affiliation: Melbourne School of Population and Global Health, and the Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Australia. Electronic address: t.nolan@unimelb.edu.au.
authors.forename: Terry
authors.initials: T
authors.lastname: Nolan
authors.affiliation: Philippine General Hospital, University of the Philippines Manila, Manila, Metro Manila, Philippines.
authors.forename: Lulu
authors.initials: L
authors.lastname: Bravo
authors.affiliation: Instituto Médico Rio Cuarto, Cordoba, Cordoba Province, Argentina.
authors.forename: Ana
authors.initials: A
authors.lastname: Ceballos
authors.affiliation: Newtown Clinical Research Centre, Johannesburg, Gauteng Province, South Africa.
authors.forename: Essack
authors.initials: E
authors.lastname: Mitha
authors.affiliation: Chris Hani Baragwanath Hospital, University of Witwatersrand, Johannesburg, Gauteng Province, South Africa.
authors.forename: Glenda
authors.initials: G
authors.lastname: Gray
authors.affiliation: Research Institute for Tropical Medicine, Muntinlupa, Metro Manila, Philippines.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Quiambao
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA.
authors.forename: Sanjay S
authors.initials: SS
authors.lastname: Patel
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bizjajeva
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Bock
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Nazaire-Bermal
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Forleo-Neto
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA.
authors.forename: Giovanni Della
authors.initials: GD
authors.lastname: Cioppa
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA.
authors.forename: Vas
authors.initials: V
authors.lastname: Narasimhan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D002675:Child, Preschool; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D009981:Influenza B virus; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D022223:Vaccines, Subunit; D013185:Squalene
keywords: (www.clinicaltrials.gov): NCT01346592; Adjuvant; Children; Fluad(®); Influenza vaccine; MF59