Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: phase I randomised trial.
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.
Stephenson
Iain
I
Infectious Diseases Unit, Leicester Royal Infirmary, Leicester LE1 5WW, UK.
Nicholson
Karl G
KG
Glück
Reinhardt
R
Mischler
Robert
R
Newman
Robert W
RW
Palache
Abraham M
AM
Verlander
Neville Q
NQ
Warburton
Fiona
F
Wood
John M
JM
Zambon
Maria C
MC
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*
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D022223:Vaccines, Subunit