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Open AccessReview

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

by Marcel Tongo 1,2,3,* and Wendy A. Burgers 1
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.
Viruses 2014, 6(10), 3968-3990; https://doi.org/10.3390/v6103968
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)
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
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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