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Viruses 2014, 6(10), 3968-3990; doi:10.3390/v6103968

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

1
Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa
2
Institute of Medical Research and Study of Medicinal Plants (IMPM), Route de l'École Normale Supérieure, Yaoundé, Cameroon
3
Current address: Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa
*
Author to whom correspondence should be addressed.
Received: 31 July 2014 / Revised: 15 October 2014 / Accepted: 18 October 2014 / Published: 23 October 2014
(This article belongs to the Special Issue AIDS Vaccine 2014)
View Full-Text   |   Download PDF [566 KB, uploaded 12 May 2015]

Abstract

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. View Full-Text
Keywords: HIV-1; diversity; broadly cross-reactive T cell responses; vaccine; immunogen design HIV-1; diversity; broadly cross-reactive T cell responses; vaccine; immunogen design
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Tongo, M.; Burgers, W.A. Challenges in the Design of a T Cell Vaccine in the Context of HIV-1 Diversity. Viruses 2014, 6, 3968-3990.

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