Human dendritic cell interactions with whole recombinant yeast: implications for HIV-1 vaccine development.
Defects in number and function of dendritic cells (DCs) have been observed during HIV-1 infection, so therapeutic HIV-1 vaccine approaches that target or activate DCs may improve vaccine immunogenicity. To determine the potential of recombinant Saccharomyces cerevisiae yeast as an HIV-1 vaccine, we investigated interactions between yeast and human DCs. Yeast induced direct phenotypic maturation of monocyte-derived DCs (MDDCs) and enriched blood myeloid DCs (mDCs), but only indirectly matured blood plasmacytoid DCs (pDCs). Yeast-pulsed MDDCs and blood mDCs produced inflammatory cytokines and stimulated strong allo-reactive T cell proliferation. Both blood DC subsets internalized yeast, and when pulsed with yeast recombinant for HIV-1 Gag protein, both stimulated in vitro expansion of Gag-specific CD8+ memory T cells. These results suggest that S. cerevisiae yeast have potent adjuvant effects on human DCs. Furthermore, recombinant yeast-derived antigens are processed by human blood DCs for MHC class-I cross-presentation. These DC-targeting characteristics of yeast suggest that it may be an effective vaccine vector for induction of HIV-1-specific cellular immune responses.
Barron
Michelle A
MA
Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Blyveis
Naomi
N
Pan
Samuel C
SC
Wilson
Cara C
CC
D016915:AIDS Vaccines / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D015683:Gene Products, gag; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D016207:Cytokines; D015683:Gene Products, gag