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Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity

The extraordinary variability of HIV-1 poses a major obstacle to vaccine development. The effectiveness of a vaccine is likely to vary dramatically in different populations infected with different HIV-1 subtypes, unless innovative vaccine immunogens are developed to protect against the range of HIV-...

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Detalles Bibliográficos
Autores principales: Tongo, Marcel, Burgers, Wendy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213573/
https://www.ncbi.nlm.nih.gov/pubmed/25341662
http://dx.doi.org/10.3390/v6103968
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author Tongo, Marcel
Burgers, Wendy A.
author_facet Tongo, Marcel
Burgers, Wendy A.
author_sort Tongo, Marcel
collection PubMed
description The extraordinary variability of HIV-1 poses a major obstacle to vaccine development. The effectiveness of a vaccine is likely to vary dramatically in different populations infected with different HIV-1 subtypes, unless innovative vaccine immunogens are developed to protect against the range of HIV-1 diversity. Immunogen design for stimulating neutralizing antibody responses focuses on “breadth” – the targeting of a handful of highly conserved neutralizing determinants on the HIV-1 Envelope protein that can recognize the majority of viruses across all HIV-1 subtypes. An effective vaccine will likely require the generation of both broadly cross-neutralizing antibodies and non-neutralizing antibodies, as well as broadly cross-reactive T cells. Several approaches have been taken to design such broadly-reactive and cross-protective T cell immunogens. Artificial sequences have been designed that reduce the genetic distance between a vaccine strain and contemporary circulating viruses; “mosaic” immunogens extend this concept to contain multiple potential T cell epitope (PTE) variants; and further efforts attempt to focus T cell immunity on highly conserved regions of the HIV-1 genome. Thus far, a number of pre-clinical and early clinical studies have been performed assessing these new immunogens. In this review, the potential use of these new immunogens is explored.
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spelling pubmed-42135732014-10-31 Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity Tongo, Marcel Burgers, Wendy A. Viruses Review The extraordinary variability of HIV-1 poses a major obstacle to vaccine development. The effectiveness of a vaccine is likely to vary dramatically in different populations infected with different HIV-1 subtypes, unless innovative vaccine immunogens are developed to protect against the range of HIV-1 diversity. Immunogen design for stimulating neutralizing antibody responses focuses on “breadth” – the targeting of a handful of highly conserved neutralizing determinants on the HIV-1 Envelope protein that can recognize the majority of viruses across all HIV-1 subtypes. An effective vaccine will likely require the generation of both broadly cross-neutralizing antibodies and non-neutralizing antibodies, as well as broadly cross-reactive T cells. Several approaches have been taken to design such broadly-reactive and cross-protective T cell immunogens. Artificial sequences have been designed that reduce the genetic distance between a vaccine strain and contemporary circulating viruses; “mosaic” immunogens extend this concept to contain multiple potential T cell epitope (PTE) variants; and further efforts attempt to focus T cell immunity on highly conserved regions of the HIV-1 genome. Thus far, a number of pre-clinical and early clinical studies have been performed assessing these new immunogens. In this review, the potential use of these new immunogens is explored. MDPI 2014-10-23 /pmc/articles/PMC4213573/ /pubmed/25341662 http://dx.doi.org/10.3390/v6103968 Text en © 2014 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tongo, Marcel
Burgers, Wendy A.
Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity
title Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity
title_full Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity
title_fullStr Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity
title_full_unstemmed Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity
title_short Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity
title_sort challenges in the design of a t cell vaccine in the context of hiv-1 diversity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213573/
https://www.ncbi.nlm.nih.gov/pubmed/25341662
http://dx.doi.org/10.3390/v6103968
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