title: MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults.
abstract: BACKGROUND
  Pathogenic avian influenza virus (H5N1) has the potential to cause a major global pandemic in humans. Safe and effective vaccines that induce immunologic memory and broad heterotypic response are needed.
  
  
  RESULTS
  Healthy adults aged 18-60 and > 60 years (n = 313 and n = 173, respectively) were randomized (1:1) to receive two primary and one booster injection of 7.5 microg or 15 microg doses of a subunit MF59-adjuvanted H5N1 (A/Vietnam/1194/2004) (clade 1) vaccine. Safety was monitored until 6 months after booster. Immunogenicity was assessed by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization assays (MN). Mild injection-site pain was the most common adverse reaction. No serious adverse events relating to the vaccine were reported. The humoral immune responses to 7.5 microg and 15 microg doses were comparable. The rates for seroprotection (HI>40; SRH>25 mm(2); MN > or = 40) after the primary vaccination ranged 72-87%. Six months after primary vaccination with the 7.5 microg dose, 18% and 21% of non-elderly and elderly adults were seroprotected; rates increased to 90% and 84%, respectively, after the booster vaccination. In the 15 microg group, seroprotection rates among non-elderly and elderly adults increased from 25% and 62% after primary vaccination to 92% and 88% after booster vaccination, respectively. A heterologous immune response to the H5N1/turkey/Turkey/05 strain was elicited after second and booster vaccinations.
  
  
  CONCLUSIONS
  Both formulations of MF59-adjuvanted influenza H5N1 vaccine were well tolerated. The European Union requirement for licensure for pre-pandemic vaccines was met by the lower dose tested. The presence of cross-reactive antibodies to a clade 2 heterologous strain demonstrates that this vaccine may be appropriate for pre-pandemic programs.
  
  
  BACKGROUND
  (ClinicalTrials.gov) NCT00311480.
authors.affiliation: Novartis Vaccines, Marburg, Germany. angelika.banzhoff@novartis.com
authors.forename: Angelika
authors.initials: A
authors.lastname: Banzhoff
authors.forename: Roberto
authors.initials: R
authors.lastname: Gasparini
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi-Pasini
authors.forename: Tommaso
authors.initials: T
authors.lastname: Staniscia
authors.forename: Paolo
authors.initials: P
authors.lastname: Durando
authors.forename: Emanuele
authors.initials: E
authors.lastname: Montomoli
authors.forename: Pier Leopoldo
authors.initials: PL
authors.lastname: Capecchi
authors.forename: Pamela
authors.initials: P
authors.lastname: Capecchi
authors.forename: Pamela
authors.initials: P
authors.lastname: di Giovanni
authors.forename: Laura
authors.initials: L
authors.lastname: Sticchi
authors.forename: Chiara
authors.initials: C
authors.lastname: Gentile
authors.forename: Anke
authors.initials: A
authors.lastname: Hilbert
authors.forename: Volker
authors.initials: V
authors.lastname: Brauer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Tilman
authors.forename: Audino
authors.initials: A
authors.lastname: Podda
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000910:Antibodies, Heterophile / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D006384:Hemagglutination / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D009500:Neutralization Tests; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000910:Antibodies, Heterophile; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene