Avian Flu Vaccine Is Immunogenic and Safe in Early-Phase Trial

A total of 275 men or women received 2 doses of 1 of 6 randomly assigned versions of Baxter's vaccine, 21 days apart. The formulations of the vaccine, produced in Vero cells, contained various doses of hemagglutinin antigen, with or without alum adjuvant. The vaccine was produced from the wild-type strain A/Vietnam/1203/2004, which was originally cultivated from a 10-year-old Vietnamese boy who died of avian influenza in 2004 (Maines TR et al. J Virol. 2005;79:11788-11800.)

The vaccine induced direct neutralizing responses to A/Vietnam/1203/2004 (clade 1), as well as cross-neutralizing responses to strains A/Indonesia/05/2005 (clade 2) and A/Hong Kong/156/1997 (clade 3). The addition of adjuvant to the vaccine did not augment immunogenic responses; maximum responses were observed with nonadjuvant formulations containing either 7.5 or 15 µg of hemagglutinin. From 9% to 27% of enrollees experienced mild injection-site pain, and 6%-31% experienced headache.

The investigators proposed that whole-virus vaccine may be more immunogenic in unvaccinated groups than split- or partial-virus vaccines, and that the use of Vero cell culture (instead of embryonated chicken eggs) will reduce vaccine-production time during a pandemic.

The NEJM—perhaps sensitive to recent reports of medical ghostwriting and the use figurehead, academic authors for company-sponsored studies—provided the following information in the Methods section:

The manuscript was written by a subgroup of industry and academic authors; all authors contributed to the content, had full access to the data, and vouch for the completeness and accuracy of the data and data analysis.

The lead author of the study is Baxter's head of Global Research and Development, Hartmut J. Ehrlich, MD; the second author is Markus Muller, MD, of the Medical University of Vienna. According to the write-up, both physicians "contributed equally" to the article.

The development of an effective avian flu vaccine for humans is unlikely to happen too soon. CDC investigators recently discovered that North American strains of avian influenza A H7 have developed host-binding affinities that are similar to those of human influenza viruses. This property may facilitate human infection with avian influenza and human-to-human transmission.

A phase 3 study of Baxter's vaccine in Austria and Germany is active, but not yet recruiting subjects.

Colorized transmission electron micrograph of avian influenza A H5N1 virus (gold) grown in MDCK cells (green) from CDC/Cynthia Goldsmith.