Vaccine development for an imminent pandemic: why we should worry, what we must do.

The avian H5N1 virus continues to evolve and poses an imminent pandemic threat. Pandemic vaccine development, however, has progressed slowly. For it to succeed, it must be based on a public health perspective that reflects the arithmetic of pandemic vaccine demand, especially by countries without vaccine companies. Clinical trials of H5N1 vaccines have been discouraging, and we must understand why the H5N1 virus is so poorly immunogenic. Antigen-sparing pandemic vaccines will be required, and future trials must identify the most effective adjuvant and determine whether whole virus vaccines will be needed. Problems related to intellectual property and concerns about several regulatory issues must be resolved. Public funding for clinical trials must be provided and firm leadership and coordination exercised by national and international (WHO) public health officials. Vaccination for an imminent pandemic requires a global perspective not only for vaccine development but also for vaccine production and distribution.