title: Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses.
abstract: T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.
authors.affiliation: Divisão de Imunologia Clínica e Alergia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Vinicius Canato
authors.initials: VC
authors.lastname: Santana
authors.affiliation: Divisão de Imunologia Clínica e Alergia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Rafael Ribeiro
authors.initials: RR
authors.lastname: Almeida
authors.affiliation: Divisão de Imunologia Clínica e Alergia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Susan Pereira
authors.initials: SP
authors.lastname: Ribeiro
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Luís Carlos de Souza
authors.initials: LC
authors.lastname: Ferreira
authors.affiliation: Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia, São Paulo, SP, Brasil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia, São Paulo, SP, Brasil.
authors.forename: Daniela Santoro
authors.initials: DS
authors.lastname: Rosa
authors.affiliation: Divisão de Imunologia Clínica e Alergia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D017124:Conserved Sequence / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008807:Mice, Inbred BALB C; D010957:Plasmids; D011485:Protein Binding / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D006684:HLA-DR Antigens; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor