The establishment and spread of highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype in birds and coincident infections in humans since 2003 have raised concerns that we may be facing an influenza pandemic caused by an H5N1 influenza virus. In this brief Opinion piece, we consider the pandemic threat posed by H5N1 viruses and review the published data on the evaluation of H5N1 vaccines in preclinical and clinical studies. HPAI H5N1 viruses have been isolated from avian species in more than 50 countries. As of 29 January 2007, 270 laboratory-confirmed cases of H5N1 infection in humans had been reported by the World Health Organization, 164 of which were fatal [1], resulting in a case fatality rate of approximately 60%.

In order to cause a pandemic, H5N1 viruses will have to acquire the ability to transmit efficiently from person to person. The H5 hemagglutinin (HA) is found in influenza viruses that typically infect avian species, so efficient personto-person spread could happen if the H5N1 virus reassorts, or exchanges genes, with circulating human influenza viruses giving rise to a virus with the H5 HA (to which the population is not immune) in a gene constellation that confers the property of transmissibility. Alternatively, efficient personto-person spread could occur if the H5N1 virus evolves and adapts to more efficient replication and transmissibility in the human population.