The main focus of my research interest is to design novel vaccine strategies for eliciting broadly neutralizing antibodies against HIV. In particular, we have constructed a chimeric protein, HA/gp41, by fusing the HIV Env gp41 in frame to the C-terminus of the HA1 subunit of an influenza virus hemagglutinin. The HA/gp41 is efficiently transported to the cell surfaces, exhibits enhanced reactivity to monoclonal antibodies 2F5 and 4E10, and more effectively induces gp41-specific antibodies compared to the HIV Env. Recently, we further evaluated the immunogenicity of HA/gp41-based DNA or virus-like particle (VLP) vaccines in guinea pigs and found that immunization with HA/gp41 DNA or VLP vaccines induced neutralizing antibodies against the conserved epitopes in gp41. Currently, we are evaluating the effectiveness of this chimeric protein vaccine in small animal models, with the goal to improve its design for optimizing its ability to induce broadly HIV neutralizing antibodies. In addition to HIV vaccine development, we are also investigating the role of regulatory T cells in modulating vaccine-induced immune responses in aging host using the mouse model.