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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-...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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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. |
format | Online Article Text |
id | pubmed-4213573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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