Challenges in the design of a T cell vaccine in the context of HIV-1 diversity

Viruses. 2014 Oct 23;6(10):3968-90. doi: 10.3390/v6103968.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AIDS Vaccines*
  • Antibodies, Neutralizing / biosynthesis
  • Cross Reactions
  • Gene Products, env / genetics
  • Genetic Variation
  • HIV Antibodies / biosynthesis
  • HIV Antigens / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / immunology*
  • Humans
  • Immunity, Cellular
  • T-Lymphocytes / immunology*

Substances

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Gene Products, env
  • HIV Antibodies
  • HIV Antigens