title: A DNA vaccine encoding multiple HIV CD4 epitopes elicits vigorous polyfunctional, long-lived CD4+ and CD8+ T cell responses.
abstract: 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. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+) T cells are important for the generation and maintenance of functional CD8(+) cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4(+) T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+)/CD8(+) T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4(+) and CD8(+) T cells that proliferate and produce any two cytokines (IFNγ/TNFα, IFNγ/IL-2 or TNFα/IL-2) simultaneously in response to HIV-1 peptides. For CD4(+) T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFNγ/TNFα/IL-2). The vaccine also generated long-lived central and effector memory CD4(+) T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+) T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+) T cells and antibody responses- elicited by other HIV immunogens.
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: Daniela Santoro
authors.initials: DS
authors.lastname: Rosa
authors.forename: Susan Pereira
authors.initials: SP
authors.lastname: Ribeiro
authors.forename: Rafael Ribeiro
authors.initials: RR
authors.lastname: Almeida
authors.forename: Eliane Conti
authors.initials: EC
authors.lastname: Mairena
authors.forename: Edilberto
authors.initials: E
authors.lastname: Postól
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015704:CD4 Antigens; D000939:Epitopes; D019444:Vaccines, DNA