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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 µg, 7.5 µg, 15 µg, or 30 µg of hemagglutinin antigen with alum adjuvant or 7.5 µg or 15 µg 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 µg and 15 µg 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 µg or 15 µg 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
[ClinicalTrials.gov]
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Source Information
From the Department of Global Research and Development, Baxter BioScience (H.J.E., G.B., S.F., A.L.-B., N.V., R.B., B.G.P., E.M.P., O.K., P.N.B.), and the Department of Clinical Pharmacology, Medical University of Vienna, Vienna General Hospital (M.M., C.J.) — both in Vienna; Changi General Hospital (H.M.L.O.) and the National University of Singapore and National University Hospital (P.A.T., D.F.) — all in Singapore; and the University of Siena, Siena, Italy (E.M.).
Drs. Ehrlich and Müller contributed equally to this article.
Address reprint requests to Dr. Müller at the Department of Clinical Pharmacology, Medical University of Vienna, Vienna General Hospital (AKH), Währinger Gürtel 18-20, 1090 Vienna, Austria, or at markus.mueller{at}meduniwien.ac.at.
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