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Initial Results of Avian Flu Vaccine Trial Reported: There’s No Reason to Celebrate Yet

By Luciana L. Borio, M.D. and John Bartlett, M.D., August 16, 2005

Initial results from an NIH-sponsored clinical trial to study the safety and immunogenicity of a vaccine designed to protect against avian influenza were reported in the media last week. This randomized, double-blind, placebo-controlled trial is testing the dose-related safety, reactogenicity, and immunogenicity of an intramuscular inactivated influenza A/H5N1 vaccine in 452 healthy adults, aged 18 to 65 years.

The study, which began in April 2005, is being conducted in two stages, with expected completion in October of this year. During the first stage, 113 subjects were randomized to receive placebo or the trial vaccine (7.5, 15, 45, or 90 micrograms in 2 doses, 28 days apart). After each dose, oral temperature, systemic, and local adverse reactions were recorded for 7 days. Serum studies for immunogenicity were obtained prior to dose 1, at the time of dose 2 (day 28), and on days 56 and 208. In the second stage, the remaining subjects received an identical protocol. Results from the first 113 subjects indicate that the vaccine containing 90 micrograms of antigen was immunogenic.

Government officials and the media reported these results as encouraging. However, there is much reason for concern. Two million doses of this vaccine have been purchased for the U.S. Strategic National Stockpile. However, the calculation that produced this number is based on an assumption that each dose requires only 15 micrograms of antigen, the standard amount contained in seasonal influenza vaccine, which is generally sufficient to generate a protective immune response. However, given that preliminary results of this study suggest that 90 micrograms are required to generate a protective immune response, the amount purchased for the stockpile will produce only 333,000 doses, a negligible supply in the face of a looming pandemic. Furthermore, the vaccine used in this study is grown in chicken eggs, which means that production can take months, and capacity is limited.

The U.S. government must move as fast as possible with dose sparing strategies to augment its current supply. This will likely require the vaccine to be formulated with an adjuvant, such as alum, to stimulate an immune response with lower doses of antigen.