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.
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20 May 2019
In the Funding section, the following statement is missing: The MACS cohort study was supported by the NIH, National Institute of Allergy and Infectious Diseases grant U01-AI35041.
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Acknowledgements
We thank Prof. Charles R. Rinaldo and Prof. Robbie B. Mailliard, both from Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, for the cells of the HIV+ patients from MACS cohort as well as helpful scientific discussions.
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This work was supported by internal funding.
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Human subject research was approved by the University of Pittsburgh Institutional Review Board.
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Bruno Douradinha is an inventor of the patent WO2018091637, partially based in this work. The other authors declare that they have no conflict of interest.
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All procedures performed in studies involving human participants’ samples were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with animals performed by any of the authors.
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Palma, M.L., Garcia-Bates, T.M., Martins, F.S. et al. Genetically engineered probiotic Saccharomyces cerevisiae strains mature human dendritic cells and stimulate Gag-specific memory CD8+ T cells ex vivo. Appl Microbiol Biotechnol 103, 5183–5192 (2019). https://doi.org/10.1007/s00253-019-09842-8
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DOI: https://doi.org/10.1007/s00253-019-09842-8