The goals of this project are: (1) To develop a vaccine which can elicit both neutralizing antibodies and cytotoxic T cells (CTL) against HIV. (2) To identify a vaccine-carrier which can reactivate memory HIV-specific B cells and cytotoxic T cells in AIDS patients with T-helper cell deficiency. We used inactivated Brucella abortus (Ba) as the carrier of choice. We demonstrated that it can elicit interferon gamma from both CD4 and CD8 cells, and Il12 from monocytes. HIV-derived proteins and peptides conjugated to Ba elicited strong neutralizing antibody responses and cytotoxic responses in normal mice. In addition, this vaccine candidate could generate anti-HIV antibodies and CTL in CD4-depleted mice as well as in class II knock-out mice. We are using several recombinant envelope proteins produced by manufacturers with active INDs. We developed quantitative assays to evaluate vaccine efficacy in the pre-clinical stage. Our vaccine development will proviide a better carrier for future HIV vaccines and could be used in second generation vaccines in the very near future.
