The above results indicate that while antibody responses against one H5N1 HA antigen or virus may well cross-react with another H5N1 HA antigen or virus, the levels of antibody responses against the autologous antigen or virus were always higher. Given the uncertainty regarding which H5N1 virus may ultimately cause a pandemic H5N1 outbreak, it is important to develop a vaccine strategy that can maximize the protection efficacy against a wide spectrum of H5N1 viruses from different clades (or subtypes). It is possible that a consensus HA antigen, or a structurally-optimized HA antigen design, can cover different H5N1 viruses at various levels of protective efficacy but there is no actual data showing that such HA antigen can achieve the maximum protective antibody responses against several H5N1 viral isolates from different clades.