Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naïve HIV-Infected Individuals
Blanco-Heredia, Juan (Instituto Nacional de Enfermedades Respiratorias (México))
Lecanda, Aarón (Instituto Nacional de Enfermedades Respiratorias (México))
Valenzuela Ponce, Humberto (Instituto Nacional de Enfermedades Respiratorias (México))
Brander, Christian (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Avila-Rios, Santiago (Instituto Nacional de Enfermedades Respiratorias (México))
Reyes Terán, Gustavo (Instituto Nacional de Enfermedades Respiratorias (México))

Date:	2016
Abstract:	Background: therapeutic HIV vaccines may prove helpful to intensify antiretroviral treatment (ART) efficacy and may be an integral part of future cure strategies. Methods: we examined IFN-gamma ELISpot responses to a panel of 218 HIV clade B consensus-based HIV protease-reverse transcriptase peptides, designed to mimic previously described and predicted cytotoxic T lymphocyte epitopes overlapping drug resistance (DR) positions, that either included the consensus sequence or the DR variant sequence, in 49 ART-naïve HIV-infected individuals. Next generation sequencing was used to assess the presence of minority DR variants in circulating viral populations. Results: although a wide spectrum of differential magnitudes of response to DR vs. WT peptide pairs was observed, responses to DR peptides were frequent and strong in the study cohort. No difference between the median magnitudes of response to DR vs. WT peptides was observed. Interestingly, of the 22 peptides that were recognized by >15% of the participants, two-thirds (64%) corresponded to DR peptides. When analysing responses per peptide pair per individual, responses to only WT (median 4 pairs/individual) or DR (median 6 pairs/individual) were more common than responses to both WT and DR (median 2 pairs/individual; p<0. 001). While the presence of ELISpot responses to WT peptides was frequently associated with the presence of the corresponding peptide sequence in the patient's virus (mean 68% of cases), responses to DR peptides were generally not associated with the presence of DR mutations in the viral population, even at low frequencies (mean 1. 4% of cases; p = 0. 0002). Conclusions: our data suggests that DR peptides are frequently immunogenic and raises the potential benefit of broadening the antigens included in a therapeutic vaccine approach to immunogenic epitopes containing common DR sequences. Further studies are needed to assess the quality of responses elicited by DR peptides.
Note:	Altres ajuts: Comisión de Equidad y Género de las Legislaturas LX-LXI i Comisión de Igualdad de Género de la Legislatura LXII de la Cámara de Diputados de la República Mexicana
Note:	Altres ajuts: SALUD-2013-01-202475
Note:	Altres ajuts: CONACyT/229424
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Sida ; Tractament ; VIH (Virus) ; Vacunes ; Antiretroviral treatment-naïve
Published in:	PloS one, Vol. 11 Núm. 1 (January 2016) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0147571
PMID: 26808823

19 p, 1.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles