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

Nature Medicine volume 7, pages 625–629 (2001)Cite this article

Abstract

There 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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Figure 1: Immunization with recombinant yeast elicits antigen-specific, T-cell protective, cytotoxic and proliferative responses.
Figure 2: DCs internalize yeast and efficiently prime MHC class I- and class II-restricted T-cell responses in vitro.
Figure 3: Yeast induce DC maturation and IL-12 secretion, and enhance the ability of DCs to present exogenous OVA protein to naive MHC class I- and class II-restricted OVA-specific T cells.

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Acknowledgements

We thank M. Schleicher, K. Hance, J. Moore and L. Sylvan for technical assistance; G. Devendra for construction of the rVV-SF2-gp160 virus; T. Potter for OT-1 TCR transgenic mice; J. DeGregory for DO11.10 TCR transgenic mouse; P. Marrack, R. Kedl, B. Kotzin and S. Rozzo for discussion and useful suggestions. B. Moss for the vaccinia virus vSC8 (rVV-lac). This work has been supported by grants from the Cancer League of Colorado (A.C.S., A.F. and R.C.D.), the Colorado Advanced Technology Institute (D.B.), and by USPHS-NIH grants AI-01459 and AI-42704 (C.W.), AI-42688 (R.C.D.), AI-43143 (R.C.D and A.F.), AI-34747 (A.F.), AI-33299 (D.K.). This study made use of the Immunology and Tissue Culture Core Facilities of the University of Colorado Cancer Center supported by USPHS-NIH grant CA-46934.

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Author notes

  1. Alex Franzusoff, Richard C. Duke and Cara C. Wilson: A.F., R.C.D and C.C.W. contributed equally to this study.

Authors and Affiliations

  1. Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA

    Andrew C. Stubbs, Kathleen S. Martin, Daniel R. Kuritzkes & Cara C. Wilson

  2. Department of Cellular and Structural Biology, University of Colorado Health Sciences Center, Denver, Colorado, USA

    Alex Franzusoff

  3. Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado, USA

    Donald Bellgrau, Richard C. Duke & Cara C. Wilson

  4. CERES Pharmaceuticals, Denver, Colorado, USA

    Claire Coeshott, Serena V. Skaates, Donald Bellgrau, Alex Franzusoff & Richard C. Duke

Authors
  1. Andrew C. Stubbs
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  2. Kathleen S. Martin
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Correspondence to Richard C. Duke or Cara C. Wilson.

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Stubbs, A., Martin, K., Coeshott, C. et al. Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity. Nat Med 7, 625–629 (2001). https://doi.org/10.1038/87974

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