title: Resistance mutations and CTL epitopes in archived HIV-1 DNA of patients on antiviral treatment: toward a new concept of vaccine.
abstract: Eleven patients responding successfully to first-line antiretroviral therapy (ART) were investigated for proviral drug resistance mutations (DRMs) in RT by ultra-deep pyrosequencing (UDPS). After molecular typing of the class I alleles A and B, the CTL epitopes in the Gag, Nef and Pol regions of the provirus were sequenced and compared to the reference HXB2 HIV-1 epitopes. They were then matched with the HLA alleles with determination of theoretical affinity (TA). For 3 patients, the results could be compared with an RNA sample of the circulating virus at initiation of therapy. Five out of 11 patients exhibited DRMs by UDPS. The issue is whether a therapeutic switch is relevant in these patients by taking into account the identity of the archived resistance mutations. When the archived CTL epitopes were determined on the basis of the HLA alleles, different patterns were observed. Some epitopes were identical to those reported for the reference with the same TA, while others were mutated with a decrease in TA. In 2 cases, an epitope was observed as a combination of subpopulations at entry and was retrieved as a single population with lower TA at success. With regard to immunological stimulation and given the variability of the archived CTL epitopes, we propose a new concept of curative vaccine based on identification of HIV-1 CTL epitopes after prior sequencing of proviral DNA and matching with HLA class I alleles.
authors.affiliation: Laboratoire de Virologie, Hôpital Pellegrin, CHU de Bordeaux et CNRS UMR 5234 (MFP), Université de Bordeaux Segalen, Bordeaux, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Papuchon
authors.forename: Patricia
authors.initials: P
authors.lastname: Pinson
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Lazaro
authors.forename: Sandrine
authors.initials: S
authors.lastname: Reigadas
authors.forename: Gwendaline
authors.initials: G
authors.lastname: Guidicelli
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
authors.forename: Didier
authors.initials: D
authors.lastname: Neau
authors.forename: Hervé
authors.initials: H
authors.lastname: Fleury
mesh_terms: D016915:AIDS Vaccines; D000483:Alleles; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005805:Genes, MHC Class I; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D018984:Epitopes, T-Lymphocyte; D054302:pol Gene Products, Human Immunodeficiency Virus