A clinical trial of a whole-virus H5N1 vaccine derived from cell culture.
BACKGROUND
Widespread infections of avian species with avian influenza H5N1 virus and its limited spread to humans suggest that the virus has the potential to cause a human influenza pandemic. An urgent need exists for an H5N1 vaccine that is effective against divergent strains of H5N1 virus.


METHODS
In a randomized, dose-escalation, phase 1 and 2 study involving six subgroups, we investigated the safety of an H5N1 whole-virus vaccine produced on Vero cell cultures and determined its ability to induce antibodies capable of neutralizing various H5N1 strains. In two visits 21 days apart, 275 volunteers between the ages of 18 and 45 years received two doses of vaccine that each contained 3.75 microg, 7.5 microg, 15 microg, or 30 microg of hemagglutinin antigen with alum adjuvant or 7.5 microg or 15 microg of hemagglutinin antigen without adjuvant. Serologic analysis was performed at baseline and on days 21 and 42.


RESULTS
The vaccine induced a neutralizing immune response not only against the clade 1 (A/Vietnam/1203/2004) virus strain but also against the clade 2 and 3 strains. The use of adjuvants did not improve the antibody response. Maximum responses to the vaccine strain were obtained with formulations containing 7.5 microg and 15 microg of hemagglutinin antigen without adjuvant. Mild pain at the injection site (in 9 to 27% of subjects) and headache (in 6 to 31% of subjects) were the most common adverse events identified for all vaccine formulations.


CONCLUSIONS
A two-dose vaccine regimen of either 7.5 microg or 15 microg of hemagglutinin antigen without adjuvant induced neutralizing antibodies against diverse H5N1 virus strains in a high percentage of subjects, suggesting that this may be a useful H5N1 vaccine. (ClinicalTrials.gov number, NCT00349141.)
Department of Global Research and Development, Baxter BioScience, Vienna, Austria.
Hartmut J
HJ
Ehrlich
Markus
M
Müller
Helen M L
HM
Oh
Paul A
PA
Tambyah
Christian
C
Joukhadar
Emanuele
E
Montomoli
Dale
D
Fisher
Greg
G
Berezuk
Sandor
S
Fritsch
Alexandra
A
Löw-Baselli
Nina
N
Vartian
Roman
R
Bobrovsky
Borislava G
BG
Pavlova
Eva Maria
EM
Pöllabauer
Otfried
O
Kistner
P Noel
PN
Barrett
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D003429:Cross Reactions; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D007273:Injections, Intramuscular / Q000009:adverse effects; D008297:Male; D009500:Neutralization Tests; D014709:Vero Cells
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines