title: Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: phase I randomised trial.
abstract: BACKGROUND
  In 1999, avian influenza A/Hong Kong/1073/99 (H9N2) virus emerged as a pandemic threat to human beings. We aimed to assess safety, tolerability, and antigenicity of whole virus and subunit H9N2 vaccines in healthy volunteers.
  
  
  METHODS
  In a phase I randomised trial we randomly assigned 60 participants to whole virus or subunit H9N2 vaccine. Two doses of 7.5 microg, 15 microg, or 30 microg haemagglutinin influenza A H9N2 vaccine, were given 3 weeks apart. We measured antibody responses by haemagglutination-inhibition and microneutralisation. The primary outcome was geometric mean antibody titre 21 days after vaccination. Analysis was per protocol.
  
  
  RESULTS
  Both vaccines were safe and well tolerated. The antibody titres after vaccination did not differ significantly between subunit and whole virus vaccine. 24 of 60 prevaccination serum samples had unexpected reactivity to H9N2, but only in participants older than 32 years, in whom one dose of either vaccine evoked antibody responses associated with protection. In participants aged 32 years or younger, antibody responses to one dose of whole virus or subunit vaccine were poor, fulfilling none of the criteria used for yearly relicensing of interpandemic vaccines. Whole virus vaccine produced a significantly higher probability of seroconversion compared with subunit virus for this age-group.
  
  
  CONCLUSIONS
  In immunologically naive patients whole-virus vaccine produced better responses than subunit vaccine. Two doses of subunit or whole virus vaccine would leave a large proportion of the naive population (< or =32 years) unprotected against A/Hong Kong/1073/99 (H9N2). Primed patients should be protected with a single dose of either vaccine.
authors.affiliation: Infectious Diseases Unit, Leicester Royal Infirmary, Leicester LE1 5WW, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Stephenson
authors.forename: Karl G
authors.initials: KG
authors.lastname: Nicholson
authors.forename: Reinhardt
authors.initials: R
authors.lastname: Glück
authors.forename: Robert
authors.initials: R
authors.lastname: Mischler
authors.forename: Robert W
authors.initials: RW
authors.lastname: Newman
authors.forename: Abraham M
authors.initials: AM
authors.lastname: Palache
authors.forename: Neville Q
authors.initials: NQ
authors.lastname: Verlander
authors.forename: Fiona
authors.initials: F
authors.lastname: Warburton
authors.forename: John M
authors.initials: JM
authors.lastname: Wood
authors.forename: Maria C
authors.initials: MC
authors.lastname: Zambon
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D018771:Arthralgia / Q000209:etiology; D006261:Headache / Q000209:etiology; D006801:Humans; D053127:Influenza A Virus, H9N2 Subtype; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D022223:Vaccines, Subunit