Nature Medicine
7, 625 - 629 (2001)
doi:10.1038/87974
Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunityAndrew C. Stubbs1, Kathleen S. Martin1, Claire Coeshott4, Serena V. Skaates4, Daniel R. Kuritzkes1, Donald Bellgrau3, 4, Alex Franzusoff2, 4, 5, Richard C. Duke3, 4, 5
& Cara C. Wilson1, 3, 51
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA
2
Department of Cellular and Structural Biology, University of Colorado Health Sciences Center, Denver, Colorado, USA
3
Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado, USA
4
CERES Pharmaceuticals, Denver, Colorado, USA
5
A.F., R.C.D and C.C.W. contributed equally to this study.
Correspondence should be addressed to Richard C. Duke cerespharm@aol.com or Cara C. Wilson cara.wilson@uchsc.eduThere is currently a need for vaccines that stimulate cell-mediated immunity—particularly that mediated by CD8+ cytotoxic T lymphocytes (CTLs)—against viral and tumor antigens. The optimal induction of cell-mediated immunity requires the presentation of antigens by specialized cells of the immune system called dendritic cells1 (DCs). DCs are unique in their ability to process exogenous antigens via the major histocompatibility complex (MHC) class I pathway2 as well as in their ability to activate naive, antigen-specific CD8+ and CD4+ T cells1,
3. Vaccine strategies that target or activate DCs in order to elicit potent CTL-mediated immunity are the subject of intense research. We report here that whole recombinant Saccharomyces cerevisiae yeast expressing tumor or HIV-1 antigens potently induced antigen-specific, CTL responses, including those mediating tumor protection, in vaccinated animals. Interactions between yeast and DCs led to DC maturation, IL-12 production and the efficient priming of MHC class I- and class II-restricted, antigen-specific T-cell responses. Yeast exerted a strong adjuvant effect, augmenting DC presentation of exogenous whole-protein antigen to MHC class I- and class II-restricted T cells. Recombinant yeast represent a novel vaccine strategy for the induction of broad-based cellular immune responses.
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