Cargando…

ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)

We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of 15 peptides originating fro...

Descripción completa

Detalles Bibliográficos
Autores principales: Fleury, Hervé, Caldato, Sabrina, Recordon-Pinson, Patricia, Thebault, Patricia, Guidicelli, Gwenda-Line, Hessamfar, Mojgan, Morlat, Philippe, Bonnet, Fabrice, Visentin, Jonathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694376/
https://www.ncbi.nlm.nih.gov/pubmed/33167335
http://dx.doi.org/10.3390/v12111256
_version_ 1783614963281035264
author Fleury, Hervé
Caldato, Sabrina
Recordon-Pinson, Patricia
Thebault, Patricia
Guidicelli, Gwenda-Line
Hessamfar, Mojgan
Morlat, Philippe
Bonnet, Fabrice
Visentin, Jonathan
author_facet Fleury, Hervé
Caldato, Sabrina
Recordon-Pinson, Patricia
Thebault, Patricia
Guidicelli, Gwenda-Line
Hessamfar, Mojgan
Morlat, Philippe
Bonnet, Fabrice
Visentin, Jonathan
author_sort Fleury, Hervé
collection PubMed
description We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of 15 peptides originating from the RT, gag and nef parts of proviral DNA. Our aim was to investigate baseline immune reactivity to the vaccine in HIV-1 chronically infected patients at success of antiretroviral therapy (ART) who would be eligible for a therapeutic vaccine. Forty-one patients were tested. Most of them had been infected with HIV-1 subtype B and all had been receiving successful ART for 2 to 20 years. The predominant HLA-A and -B alleles were those of a Caucasian population. ELISPOT was carried out using the HFVAC peptides. In 22 patients, the PD-1 marker was investigated on CD4+ and CD8+ T cells by flow cytometry in order to evaluate global T cell exhaustion. ELISPOT positivity was 65% overall and 69% in patients exhibiting at least one HLA allele fitting with HFVAC. The percentages of CD4+ and CD8+ T cells expressing PD-1 were high (median values 23.70 and 32.60, respectively), but did not seem to be associated with an impairment of the immune response investigated in vitro. In conclusion, reactivity to HFVAC was high in this ART-treated population with dominant HLA alleles, despite potential cellular exhaustion associated with the PD-1 marker.
format Online
Article
Text
id pubmed-7694376
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76943762020-11-28 ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study) Fleury, Hervé Caldato, Sabrina Recordon-Pinson, Patricia Thebault, Patricia Guidicelli, Gwenda-Line Hessamfar, Mojgan Morlat, Philippe Bonnet, Fabrice Visentin, Jonathan Viruses Brief Report We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of 15 peptides originating from the RT, gag and nef parts of proviral DNA. Our aim was to investigate baseline immune reactivity to the vaccine in HIV-1 chronically infected patients at success of antiretroviral therapy (ART) who would be eligible for a therapeutic vaccine. Forty-one patients were tested. Most of them had been infected with HIV-1 subtype B and all had been receiving successful ART for 2 to 20 years. The predominant HLA-A and -B alleles were those of a Caucasian population. ELISPOT was carried out using the HFVAC peptides. In 22 patients, the PD-1 marker was investigated on CD4+ and CD8+ T cells by flow cytometry in order to evaluate global T cell exhaustion. ELISPOT positivity was 65% overall and 69% in patients exhibiting at least one HLA allele fitting with HFVAC. The percentages of CD4+ and CD8+ T cells expressing PD-1 were high (median values 23.70 and 32.60, respectively), but did not seem to be associated with an impairment of the immune response investigated in vitro. In conclusion, reactivity to HFVAC was high in this ART-treated population with dominant HLA alleles, despite potential cellular exhaustion associated with the PD-1 marker. MDPI 2020-11-05 /pmc/articles/PMC7694376/ /pubmed/33167335 http://dx.doi.org/10.3390/v12111256 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Fleury, Hervé
Caldato, Sabrina
Recordon-Pinson, Patricia
Thebault, Patricia
Guidicelli, Gwenda-Line
Hessamfar, Mojgan
Morlat, Philippe
Bonnet, Fabrice
Visentin, Jonathan
ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)
title ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)
title_full ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)
title_fullStr ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)
title_full_unstemmed ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)
title_short ART-Treated Patients Exhibit an Adaptive Immune Response against the HFVAC Peptides, a Potential HIV-1 Therapeutic Vaccine (Provir/Latitude45 Study)
title_sort art-treated patients exhibit an adaptive immune response against the hfvac peptides, a potential hiv-1 therapeutic vaccine (provir/latitude45 study)
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694376/
https://www.ncbi.nlm.nih.gov/pubmed/33167335
http://dx.doi.org/10.3390/v12111256
work_keys_str_mv AT fleuryherve arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study
AT caldatosabrina arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study
AT recordonpinsonpatricia arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study
AT thebaultpatricia arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study
AT guidicelligwendaline arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study
AT hessamfarmojgan arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study
AT morlatphilippe arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study
AT bonnetfabrice arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study
AT visentinjonathan arttreatedpatientsexhibitanadaptiveimmuneresponseagainstthehfvacpeptidesapotentialhiv1therapeuticvaccineprovirlatitude45study