Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.

<h4>Background</h4>Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.<h4>Methods</h4>We have evaluated the specific T cell response against di...

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Autores principales: Alberto Crespo Guardo, Carmen Alvarez-Fernández, Hodei Arberas, Javier García-Pérez, Felipe García, Manuel Enric Bargalló, María José Maleno, José María Gatell, Beatriz Mothe, José Alcami, Sonsoles Sánchez-Palomino, Montserrat Plana
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:8b7129dfa144400c92d422470609605b2021-11-18T07:53:24ZUse of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.1932-620310.1371/journal.pone.0058927https://doaj.org/article/8b7129dfa144400c92d422470609605b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516578/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.<h4>Methods</h4>We have evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnv[AC10] and NL4-3/ΔRT/ΔEnv[Bal]) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry.<h4>Results</h4>The differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: "full-responders" (positive response against both viral particles), "partial-responders" (positive response only against NL4-3/ΔRT virions) and "non-responders" (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals.<h4>Conclusions</h4>In summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and in vaccine trials, by a feasible, simply, effective and low cost assay.Alberto Crespo GuardoCarmen Alvarez-FernándezHodei ArberasJavier García-PérezFelipe GarcíaManuel Enric BargallóMaría José MalenoJosé María GatellBeatriz MotheJosé AlcamiSonsoles Sánchez-PalominoMontserrat PlanaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58927 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Alberto Crespo Guardo
Carmen Alvarez-Fernández
Hodei Arberas
Javier García-Pérez
Felipe García
Manuel Enric Bargalló
María José Maleno
José María Gatell
Beatriz Mothe
José Alcami
Sonsoles Sánchez-Palomino
Montserrat Plana
Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.
description <h4>Background</h4>Generation of new reagents that can be used to screen or monitor HIV-1-specific responses constituted an interesting field in the development of HIV vaccines to improve their efficacy.<h4>Methods</h4>We have evaluated the specific T cell response against different types of NL4-3 virions (including NL4-3 aldrithiol-2 treated, NL4-3/ΔRT and R5 envelopes: NL4-3/ΔRT/ΔEnv[AC10] and NL4-3/ΔRT/ΔEnv[Bal]) and against pools of overlapping peptides (15 mer) encompassing the HIV-1 Gag and Nef regions. Cryopreserved PBMC from a subset of 69 chronic asymptomatic HIV positive individuals have been employed using different techniques including IFN-γ ELISPOT assay, surface activation markers and intracellular cytokine staining (ICS) by flow cytometry.<h4>Results</h4>The differential response obtained against NL4-3 aldrithiol-2 treated and NL4-3/ΔRT virions (25% vs 55%, respectively) allow us to divide the population in three groups: "full-responders" (positive response against both viral particles), "partial-responders" (positive response only against NL4-3/ΔRT virions) and "non-responders" (negative responses). There was no difference between X4 and R5 envelopes. The magnitude of the total responses was higher against NL4-3/ΔRT and was positively correlated with gender and inverse correlated with viral load. On the contrary CD4+ T cell count was not associated with this response. In any case responses to the viruses tended to be lower in magnitude than those detected by the overlapping peptides tested. Finally we have found an increased frequency of HLA-B27 allele (23% vs 9%) and a significant reduction in some activation markers (CD69 and CD38) on T cells surface in responders vs non-responders individuals.<h4>Conclusions</h4>In summary these virions could be considered as alternative and useful reagents for screening HIV-1-specific T cell responses in HIV exposed uninfected people, HIV infected patients and to assess immunogenicity of new prototypes both in vitro and in vaccine trials, by a feasible, simply, effective and low cost assay.
format article
author Alberto Crespo Guardo
Carmen Alvarez-Fernández
Hodei Arberas
Javier García-Pérez
Felipe García
Manuel Enric Bargalló
María José Maleno
José María Gatell
Beatriz Mothe
José Alcami
Sonsoles Sánchez-Palomino
Montserrat Plana
author_facet Alberto Crespo Guardo
Carmen Alvarez-Fernández
Hodei Arberas
Javier García-Pérez
Felipe García
Manuel Enric Bargalló
María José Maleno
José María Gatell
Beatriz Mothe
José Alcami
Sonsoles Sánchez-Palomino
Montserrat Plana
author_sort Alberto Crespo Guardo
title Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.
title_short Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.
title_full Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.
title_fullStr Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.
title_full_unstemmed Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.
title_sort use of rt-defective hiv virions: new tool to evaluate specific response in chronic asymptomatic hiv-infected individuals.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/8b7129dfa144400c92d422470609605b
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