Provir/Latitude 45 study: A step towards a multi-epitopic CTL vaccine designed on archived HIV-1 DNA and according to dominant HLA I alleles
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AbstractOne of the approaches by which the scientific community is seeking to cure HIV is the use of therapeutic vaccination. Previous studies have highlighted the importance of the virus-specific CD8+ T cell cytotoxic responses for the immune control of HIV and have oriented research on vaccine constructs based on CTL epitopes from circulating HIV-1 strains. The clinical trials with therapeutic vaccines to date have had limited success likely due to (i) a discrepancy between archived CTL epitopes in the viral reservoir and those in circulating viruses before antiretroviral therapy (ART) initiation and (ii) the lack of strong affinity between the selected CTL epitopes and the HLA grooves for presentation to CD8+ cells. To overcome these limitations, we launched the Provir/Latitude 45 study to identify conserved CTL epitopes in archived HIV-1 DNA according to the HLA class I alleles of aviremic patients, most of whom are under ART. The near full-length genomes or Gag, Pol and Nef regions of proviral DNA were sequenced by Sanger and/or Next Generation Sequencing (NGS). The HLA-A and B alleles were defined by NGS or molecular analysis. The TuTuGenetics software, which moves a sliding window of 8 to 10 amino acids through the amino acid alignment, was combined with the Immune Epitope Data Base (IEDB) to automatically calculate the theoretical binding affinity of identified epitopes to the HLA alleles for each individual. We identified 15 conserved epitopes in Pol (11), Gag (3), and Nef (1) according to their potential presentation by the dominant HLA-A and B alleles and now propose to use the corresponding conserved peptides in a multi-epitopic vaccine (HLA-fitted VAC, HFVAC). Copyright 2019 Tumiotto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SponsorsHF received a grant from Merck Sharp and Dohme (DS-2016-0005) and financial contribution from GERMATAN (groupe d'etudes et de recherche sur les maladies animales et les anthropozoonoses). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywordcombination antiretroviral therapies
HLA class 1 alleles
human leukocyte antigens
Antiretroviral Therapy, Highly Active
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85062192263&doi=10.1371%2fjournal.pone.0212347&partnerID=40&md5=750f8936d5951464bc7a18f06775ebed; http://hdl.handle.net/10713/8709