Genetically engineered probiotic Saccharomyces cerevisiae strains mature human dendritic cells and stimulate Gag-specific memory CD8+ T cells ex vivo

Mariana L. Palma, Tatiana M. Garcia-Bates, Flaviano S. Martins, Bruno Douradinha

Research output: Contribution to journalArticlepeer-review

Abstract

Recombinant Saccharomyces cerevisiae strains expressing HIV antigens have shown promising pre-clinical results. Probiotic S. cerevisiae strains naturally induce gut immunity; thus, genetically engineered probiotic strains could be used to stimulate immune responses against HIV in the mucosa. Probiotic strains have a higher rate of heterologous protein production, meaning higher antigen’s epitope expression levels per yeast cell. We expressed HIV-1 Gag protein in the probiotic yeasts’ surface, which was eagerly phagocytosed by and induced type 1 polarization of human monocyte-derived dendritic cells (DCs) from healthy donors in vitro. We further matured DCs derived from HIV-1+ donors with transformed yeasts and incubated them with autologous T cells. Only DCs matured with Gag-expressing probiotic strains were able to efficiently present antigen to CD8+ T cells and induced their clonal expansion. Our results show that genetically engineered probiotic S. cerevisiae strains are a promising vaccination strategy against HIV.

Original languageEnglish
Pages (from-to)5183-5192
Number of pages10
JournalApplied Microbiology and Biotechnology
Volume103
Issue number13
DOIs
Publication statusPublished - Jul 4 2019

Keywords

  • Gag antigen
  • HIV vaccine
  • Probiotics
  • Saccharomyces boulardii
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

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