title: Challenges in the design of a T cell vaccine in the context of HIV-1 diversity.
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.
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. TNGAIM001@myuct.ac.za.
authors.forename: Marcel
authors.initials: M
authors.lastname: Tongo
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. wendy.burgers@uct.ac.za.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Burgers
mesh_terms: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D003429:Cross Reactions; D015686:Gene Products, env / Q000235:genetics; D014644:Genetic Variation; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens