Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity

There is currently a need for vaccines that stimulate cell-mediated immunit y-particularly that mediated by CD8(+) cytotoxic T lymphocytes (CTLs)-again st viral and tumor antigens. The optimal induction of cell-mediated immunit y requires the presentation of antigens by specialized cells of the immune system called dendritic cells(1) (DCs). DCs are unique in their ability to process exogenous antigens via the major histocompatibility complex (MHC) c lass I pathway(2) as well as in their ability to activate naive, antigen-sp ecific CD8(+) and CD4(+) T cells(1,3). Vaccine strategies that target or ac tivate DCs in order to elicit potent CTL-mediated immunity are the subject of intense research. We report here that whole recombinant Saccharomyces ce revisiae yeast expressing tumor or HIV-1 antigens potently induced antigen- specific, CTL responses, including those mediating tumor protection, in vac cinated animals. Interactions between yeast and DCs led to DC maturation, I L-12 production and the efficient priming of MHC class I- and class II-rest ricted, antigen-specific T-cell responses. Yeast exerted a strong adjuvant effect, augmenting DC presentation of exogenous whole-protein antigen to MH C class I- and class II-restricted T cells. Recombinant yeast represent a n ovel vaccine strategy for the induction of broad-based cellular immune resp onses.