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A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART
TRIAL DESIGN: Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm(3) and undetectable v...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636254/ https://www.ncbi.nlm.nih.gov/pubmed/26544853 http://dx.doi.org/10.1371/journal.pone.0141456 |
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author | Gómez, Carmen Elena Perdiguero, Beatriz García-Arriaza, Juan Cepeda, Victoria Sánchez-Sorzano, Carlos Óscar Mothe, Beatriz Jiménez, José Luis Muñoz-Fernández, María Ángeles Gatell, Jose M. López Bernaldo de Quirós, Juan Carlos Brander, Christian García, Felipe Esteban, Mariano |
author_facet | Gómez, Carmen Elena Perdiguero, Beatriz García-Arriaza, Juan Cepeda, Victoria Sánchez-Sorzano, Carlos Óscar Mothe, Beatriz Jiménez, José Luis Muñoz-Fernández, María Ángeles Gatell, Jose M. López Bernaldo de Quirós, Juan Carlos Brander, Christian García, Felipe Esteban, Mariano |
author_sort | Gómez, Carmen Elena |
collection | PubMed |
description | TRIAL DESIGN: Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm(3) and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART. METHODS: The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination. RESULTS: MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8(+) T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses. CONCLUSION: MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01571466 |
format | Online Article Text |
id | pubmed-4636254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46362542015-11-13 A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART Gómez, Carmen Elena Perdiguero, Beatriz García-Arriaza, Juan Cepeda, Victoria Sánchez-Sorzano, Carlos Óscar Mothe, Beatriz Jiménez, José Luis Muñoz-Fernández, María Ángeles Gatell, Jose M. López Bernaldo de Quirós, Juan Carlos Brander, Christian García, Felipe Esteban, Mariano PLoS One Research Article TRIAL DESIGN: Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm(3) and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART. METHODS: The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination. RESULTS: MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8(+) T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses. CONCLUSION: MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01571466 Public Library of Science 2015-11-06 /pmc/articles/PMC4636254/ /pubmed/26544853 http://dx.doi.org/10.1371/journal.pone.0141456 Text en © 2015 Gómez et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gómez, Carmen Elena Perdiguero, Beatriz García-Arriaza, Juan Cepeda, Victoria Sánchez-Sorzano, Carlos Óscar Mothe, Beatriz Jiménez, José Luis Muñoz-Fernández, María Ángeles Gatell, Jose M. López Bernaldo de Quirós, Juan Carlos Brander, Christian García, Felipe Esteban, Mariano A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART |
title | A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART |
title_full | A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART |
title_fullStr | A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART |
title_full_unstemmed | A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART |
title_short | A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART |
title_sort | phase i randomized therapeutic mva-b vaccination improves the magnitude and quality of the t cell immune responses in hiv-1-infected subjects on haart |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636254/ https://www.ncbi.nlm.nih.gov/pubmed/26544853 http://dx.doi.org/10.1371/journal.pone.0141456 |
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