title: A vaccine encoding conserved promiscuous HIV CD4 epitopes induces broad T cell responses in mice transgenic to multiple common HLA class II molecules.
abstract: Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding) B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8). Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.
authors.affiliation: Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Susan Pereira
authors.initials: SP
authors.lastname: Ribeiro
authors.forename: Daniela Santoro
authors.initials: DS
authors.lastname: Rosa
authors.forename: Simone Gonçalves
authors.initials: SG
authors.lastname: Fonseca
authors.forename: Eliane Conti
authors.initials: EC
authors.lastname: Mairena
authors.forename: Edilberto
authors.initials: E
authors.lastname: Postól
authors.forename: Sergio Costa
authors.initials: SC
authors.lastname: Oliveira
authors.forename: Luiza
authors.initials: L
authors.lastname: Guilherme
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D000949:Histocompatibility Antigens Class II