title: Novel approaches in polyepitope T-cell vaccine development against HIV-1.
abstract: RV144 clinical trial was modestly effective in preventing HIV infection. New alternative approaches are needed to design improved HIV-1 vaccines and their delivery strategies. One of these approaches is construction of synthetic polyepitope HIV-1 immunogen using protective T- and B-cell epitopes that can induce broadly neutralizing antibodies and responses of cytotoxic (CD8(+) CTL) and helpers (CD4(+) Th) T-lymphocytes. This approach seems to be promising for designing of new generation of vaccines against HIV-1, enables in theory to cope with HIV-1 antigenic variability, focuses immune responses on protective determinants and enables to exclude from the vaccine compound that can induce autoantibodies or antibodies enhancing HIV-1 infectivity. Herein, the authors will focus on construction and rational design of polyepitope T-cell HIV-1 immunogens and their delivery, including: advantages and disadvantages of existing T-cell epitope prediction methods; features of organization of polyepitope immunogens, which can generate high-level CD8(+) and CD4(+) T-lymphocyte responses; the strategies to optimize efficient processing, presentation and immunogenicity of polyepitope constructs; original software to design polyepitope immunogens; and delivery vectors as well as mucosal strategies of vaccination. This new knowledge may bring us a one step closer to developing an effective T-cell vaccine against HIV-1, other chronic viral infections and cancer.
authors.affiliation: State Research Center of Virology and Biotechnology "Vector", Koltsovo, Novosibirsk region, 630559, Russia.
authors.forename: Larisa I
authors.initials: LI
authors.lastname: Karpenko
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Bazhan
authors.forename: Denis V
authors.initials: DV
authors.lastname: Antonets
authors.forename: Igor M
authors.initials: IM
authors.lastname: Belyakov
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019295:Computational Biology / Q000639:trends; D055808:Drug Discovery / Q000639:trends; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D014614:Vaccines, Synthetic