title: Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza.
abstract: BACKGROUND
  In 1997, pathogenic avian influenza A/Hong Kong/97 (H5N1) viruses emerged as a pandemic threat to human beings. A non-pathogenic variant, influenza A/Duck/Singapore/97 (H5N3), was identified as a leading vaccine candidate. We did an observer-blind, phase I, randomised trial in healthy volunteers to assess safety, tolerability, and antigenicity of MF59-adjuvanted and non-adjuvanted vaccines.
  
  
  METHODS
  32 participants were randomly assigned MF59, and 33 non-adjuvanted vaccine. Two doses were given 3 weeks apart, of 7.5, 15, or 30 microg haemagglutinin surface-antigen influenza A H5N3 vaccine. Antibody responses were measured by haemagglutination inhibition, microneutralisation, and single radial haemolysis (SRH). The primary outcome was geometric mean antibody titre 21 days after vaccination.
  
  
  RESULTS
  The A/Duck/SIngapore vaccines were safe and well tolerated. Antibody response to non-adjuvanted vaccine was poor, the best response occurring after two 30 microgram doses: one, four, four, and one person of eleven seroconverted by haemagglutination inhibition, microneutralisation, H5N3 SRH, and H5N1 SRH, respectively. The geometric mean titres of antibody, and seroconversion rates, were significantly higher after MF59 adjuvanted vaccine. Two 7.5 microg doses of MF59 adjuvanted vaccine gave the highest seroconversion rates: haemagglutination inhibition, six of ten; microneutralisation, eight of ten; H5N3 SRH, ten of ten; H5N1 SRH, nine of ten. Geometric mean titre of antibody to the pathogenic virus, A/Hong Kong/489/97 (H5N1), was about half that to A/Duck/Singapore virus.
  
  
  CONCLUSIONS
  Non-adjuvanted A/Duck/Singapore/97 (H5N3) vaccines are poorly immunogenic and doses of 7.5-30 microg haemagglutinin alone are unlikely to give protection from A/Hong Kong/97 (H5N1) virus. Addition of MF59 to A/Duck/Singapore/97 vaccines boost the antibody response to protection levels. Our findings have implications for development and assessment of vaccines for future pandemics.
authors: Infectious Diseases Unit, Leicester Royal Infirmary, LE1 5WW, Leicester, UK. karlgnicholson@doctors.org.uk
authors: K G
authors: KG
authors: Nicholson
authors: A E
authors: AE
authors: Colegate
authors: A
authors: A
authors: Podda
authors: I
authors: I
authors: Stephenson
authors: J
authors: J
authors: Wood
authors: E
authors: E
authors: Ypma
authors: M C
authors: MC
authors: Zambon
mesh_terms: D000328:Adult; D000818:Animals; D000917:Antibody Formation; D004372:Ducks / Q000821:virology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D053124:Influenza A Virus, H5N1 Subtype; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D015164:Vaccines, Inactivated; D013185:Squalene