CTL Epitopes in Archived HIV-1 DNA of Patients at Success of cART and According to their HLA Alleles; the Provir/Latitude Project

The scientific and medical community is seeking to cure HIV. Several pathways have been or are being explored: cART intensification, latency reversal agents, monoclonal antibodies, immunomodulators , gene therapy and therapeutic vaccination. Viro-immunological studies have demonstrated the importance of the CD8+ T cell cytotoxic response and have mainly oriented research on vaccine constructs towards this type of response. The results of the vaccine trials are clearly not commensurate with the hope placed in them. Our team and others (Deng et al, Nature 2015) have drawn attention to the discrepancy between the archived CTL epitopes and the theoretical recognition by the HLA alleles I.
Provir/Latitude 45 project aims to identify conserved HIV-1 CTL epitopes in archived DNA of patients at success of cART according to their potential presentation by the HLA alleles; patients are recruited in Bordeaux and Brazil (Rio de Janeiro , Rio do Sul) ; the proviral DNA is sequenced (Sanger and or/NGS on the whole length or at least on pol, gag and nef regions); the HLA alleles are determined by molecular techniques (including NGS); a software (TuTuGenetics) has been set up which is able to link the data from sequencing (Sanger or NGS), HLA alleles , the Los Alamos HIV database and the IEDB simulator. It yields automatically a list per isolate of CTL epitopes and their potential affinity for the HLA grooves. Taking into account the dominant HLA alleles of the investigated population, we plan to define a list of CTL peptides which could be introduced into a vaccine composition.
Provir has been extended to a cooperation with McGill and CHUM in Montreal, Canada. We plan to compare the archived CTL epitopes in archived proviral DNA of PBMC and Gut Associated Lymphoid tissues (GLAT) in patients at success of cART using NGS technique and the TuTuGenetics software.
Provir/Latitude 45 project is granted by Merck Sharp and Dohme (MSD Avenir DS-2016-005)