According to phylogenetic analysis, H5N1 viruses can be divided into 10 clades (0-9). Since 1997, humans have mainly been infected by H5N1 viruses from clades 0, 1, and 2, although there have also been reports of infection by clade 7 virus [5] . Clade 2 is the most complicated in its genetic evolution and has been further divided into five subclades (2.1 to 2.5). In the current study, While progress has been made in reducing the number of required immunizations during vaccination with inactivated H5N1 vaccines by incorporating various adjuvants into the vaccine formulations, a major next-step for H5N1 vaccine research is to determine to what degree the immunity elicited by one H5 avian influenza vaccine (currently, many candidate H5N1 vaccines were developed based on a clade 1 virus (A/VietNam/1203/2004)) can cross-protect against H5N1 viruses from other clades. Unlike human Type A influenza viruses (H1 or H3 serotypes), any potential pandemic caused by an H5N1 virus will be of avian origin and, in theory, any of the current known H5N1 avian viruses may jump to the human population leading to the next pandemic. Therefore, a systemic examination on the cross-protection among HA antigens from different clades is needed for strategic planning to determine whether more than one H5N1 vaccine is needed based on the analysis of protection profiles, and if so, what particular viral strains should be selected to provide the maximum breadth of protection.