title: Multiple Approaches for Increasing the Immunogenicity of an Epitope-Based Anti-HIV Vaccine.
abstract: The development of a highly effective vaccine against the human immunodeficiency virus (HIV) will likely be based on rational vaccine design, since traditional vaccine approaches have failed so far. In recent years, an understanding of what type of immune response is protective against infection and/or disease facilitated vaccine design. T cell-based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. In this context, CD4(+) T cells play a direct cytotoxic role and are also important for the generation and maintenance of functional CD8(+) T and B cell responses. The use of MHC-binding algorithms has allowed the identification of novel CD4(+) T cell epitopes that could be used in vaccine design, the so-called epitope-driven vaccine design. Epitope-based vaccines have the ability to focus the immune response on highly antigenic, conserved epitopes that are fully recognized by the target population. We have recently mapped a set of conserved multiple HLA-DR-binding HIV-1 CD4 epitopes and observed interferon (IFN)-γ-producing CD4(+) T cells when we tested these peptides in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals. We then designed multiepitopic DNA vaccines that induced broad and polyfunctional T cell responses in immunized mice. In this review we will focus on alternative strategies to increase the immunogenicity of an epitope-based vaccine against HIV infection.
authors.affiliation: 1 Departament of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP) , São Paulo, Brazil .|2 Institute for Investigation in Immunology-INCT , São Paulo, Brazil .
authors.forename: Daniela Santoro
authors.initials: DS
authors.lastname: Rosa
authors.affiliation: 2 Institute for Investigation in Immunology-INCT , São Paulo, Brazil .|3 Laboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine , São Paulo, Brazil .
authors.forename: Susan Pereira
authors.initials: SP
authors.lastname: Ribeiro
authors.affiliation: 4 Institute for Tropical Pathology and Public Health, Federal University of Goiás , Goiás, Brazil .
authors.forename: Simone Gonçalves
authors.initials: SG
authors.lastname: Fonseca
authors.affiliation: 3 Laboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine , São Paulo, Brazil .|4 Institute for Tropical Pathology and Public Health, Federal University of Goiás , Goiás, Brazil .
authors.forename: Rafael Ribeiro
authors.initials: RR
authors.lastname: Almeida
authors.affiliation: 3 Laboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine , São Paulo, Brazil .|4 Institute for Tropical Pathology and Public Health, Federal University of Goiás , Goiás, Brazil .
authors.forename: Vinicius Canato
authors.initials: VC
authors.lastname: Santana
authors.affiliation: 1 Departament of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP) , São Paulo, Brazil .|2 Institute for Investigation in Immunology-INCT , São Paulo, Brazil .
authors.forename: Juliana de Souza
authors.initials: Jde S
authors.lastname: Apostólico
authors.affiliation: 2 Institute for Investigation in Immunology-INCT , São Paulo, Brazil .|5 Heart Institute (InCor), University of São Paulo School of Medicine , São Paulo, Brazil .
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: 2 Institute for Investigation in Immunology-INCT , São Paulo, Brazil .|3 Laboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine , São Paulo, Brazil .|5 Heart Institute (InCor), University of São Paulo School of Medicine , São Paulo, Brazil .
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D023421:Models, Animal; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D019444:Vaccines, DNA; D007371:Interferon-gamma