Applied Microbiology and Biotechnology

, Volume 103, Issue 13, pp 5183–5192 | Cite as

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 DouradinhaEmail author
Biotechnological products and process engineering


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.


HIV vaccine Saccharomyces cerevisiae Saccharomyces boulardii Probiotics Gag antigen 



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.


This work was supported by internal funding.

Compliance with ethical standards

Human subject research was approved by the University of Pittsburgh Institutional Review Board.

Conflict of interest

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.

Ethical statement

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.

Supplementary material

253_2019_9842_MOESM1_ESM.pdf (738 kb)
ESM 1 (PDF 737 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Infectious Diseases and MicrobiologyUniversity of Pittsburgh Graduate School of Public HealthPittsburghUSA
  2. 2.Departamento de Microbiologia, Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Unità di Medicina Rigenerativa ed ImmunologiaFondazione Ri.MED c/o IRCCS-ISMETTPalermoItaly

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