Cytotoxic T cell (CTL)-mediated immunity is considered to play a major role in reducing viral load early in HIV infection, and in slowing the rate of progression to AIDS. Most of the current HIV vaccines, consisting of HIV-derived proteins or killed virus, elicit strong antibody responses but are poor at inducing CTL-mediated immunity. The investigators have developed a novel, HIV vaccine delivery system (HIVAX) consisting of live, recombinant Saccharomyces cerevisiae expressing the gp16O protein, that elicits antigen-specific helper and cytotoxic T cell activity. The important characteristics of the proposed vaccine are that it: (i) contains no infectious material; (ii) does not require adjuvants; (iii) stimulates both cell-mediated and humoral immunity; (iv) may be orally active; and (v) can be readily engineered using recombinant DNA technology to express three or more protein antigens.
The specific aims of this proposal are: (1) to perform a comparative study of the types of immunity elicited when HIVAX is administered by systemic or mucosal routes in mice. This work will establish the most efficient routes and dosage of vaccine application for future pre-clinical and clinical trials; (2) to investigate the mechanism of HIVAX induction of CTL activity. The role of helper T cells, antigen presentation via class II major histocompatibility complex (MHC) molecules, and macrophage presentation of the HIVAX antigens via class I MHC molecules in CTL mediated immunity, will be assessed. This information will be critical for elucidating how the vaccine works and may lead to improved versions of the vaccine; and (3) to determine biological efficacy of the vaccine for eliciting protective immunity in mice. A tumor vaccine model will be investigated by testing whether tumor cells expressing gp 160 fail to establish tumors in vaccinated mice.
| Stubbs, A C; Martin, K S; Coeshott, C et al. (2001) Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity. Nat Med 7:625-9 |
