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Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens

BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8(+) T-cell responses. The central theorem of o...

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Autores principales: Moyo, Nathifa, Borthwick, Nicola J., Wee, Edmund G., Capucci, Silvia, Crook, Alison, Dorrell, Lucy, Hanke, Tomáš
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515449/
https://www.ncbi.nlm.nih.gov/pubmed/28719652
http://dx.doi.org/10.1371/journal.pone.0181382
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author Moyo, Nathifa
Borthwick, Nicola J.
Wee, Edmund G.
Capucci, Silvia
Crook, Alison
Dorrell, Lucy
Hanke, Tomáš
author_facet Moyo, Nathifa
Borthwick, Nicola J.
Wee, Edmund G.
Capucci, Silvia
Crook, Alison
Dorrell, Lucy
Hanke, Tomáš
author_sort Moyo, Nathifa
collection PubMed
description BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8(+) T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8(+) T cells capable of in vitro HIV-1 inhibition. Here, we assessed the durability of these responses. METHODS: Vaccine recipients in trial HIV-CORE 002 were invited to provide a blood sample at 1 and 2 years after vaccination. Their PBMCs were tested in IFN-γ ELISPOT, 25-analyte Luminex, CFSE proliferation and intracellular cytokine staining assays, the last enhanced by HLA-peptide dextramer analysis. RESULTS: 12/12 (1 year) and 8/8 (2 years) returning subjects had median (range) of 990 (150–2495) and 763 (70–1745) IFN-γ SFU/10(6) PBMC specific for HIVconsv, respectively, and recognized 5 (1–6) out of 6 peptide pools at 2 years. Over one-half of the HIVconsv–specific cells expressed at least 3 functions IFN-γ, TNF-α and CD107a, and were capable of proliferation. Among dextramer-reactive cells, naïve, transitional, effector and terminally differentiated memory subsets were similarly represented. CONCLUSIONS: First generation HIVconsv vaccine induced human T cells, which were plurifunctional and persisted for at least 2 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT01151319
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spelling pubmed-55154492017-08-07 Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens Moyo, Nathifa Borthwick, Nicola J. Wee, Edmund G. Capucci, Silvia Crook, Alison Dorrell, Lucy Hanke, Tomáš PLoS One Research Article BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8(+) T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8(+) T cells capable of in vitro HIV-1 inhibition. Here, we assessed the durability of these responses. METHODS: Vaccine recipients in trial HIV-CORE 002 were invited to provide a blood sample at 1 and 2 years after vaccination. Their PBMCs were tested in IFN-γ ELISPOT, 25-analyte Luminex, CFSE proliferation and intracellular cytokine staining assays, the last enhanced by HLA-peptide dextramer analysis. RESULTS: 12/12 (1 year) and 8/8 (2 years) returning subjects had median (range) of 990 (150–2495) and 763 (70–1745) IFN-γ SFU/10(6) PBMC specific for HIVconsv, respectively, and recognized 5 (1–6) out of 6 peptide pools at 2 years. Over one-half of the HIVconsv–specific cells expressed at least 3 functions IFN-γ, TNF-α and CD107a, and were capable of proliferation. Among dextramer-reactive cells, naïve, transitional, effector and terminally differentiated memory subsets were similarly represented. CONCLUSIONS: First generation HIVconsv vaccine induced human T cells, which were plurifunctional and persisted for at least 2 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT01151319 Public Library of Science 2017-07-18 /pmc/articles/PMC5515449/ /pubmed/28719652 http://dx.doi.org/10.1371/journal.pone.0181382 Text en © 2017 Moyo 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Moyo, Nathifa
Borthwick, Nicola J.
Wee, Edmund G.
Capucci, Silvia
Crook, Alison
Dorrell, Lucy
Hanke, Tomáš
Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens
title Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens
title_full Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens
title_fullStr Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens
title_full_unstemmed Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens
title_short Long-term follow up of human T-cell responses to conserved HIV-1 regions elicited by DNA/simian adenovirus/MVA vaccine regimens
title_sort long-term follow up of human t-cell responses to conserved hiv-1 regions elicited by dna/simian adenovirus/mva vaccine regimens
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515449/
https://www.ncbi.nlm.nih.gov/pubmed/28719652
http://dx.doi.org/10.1371/journal.pone.0181382
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