Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses

• Published in: Memórias do Instituto Oswaldo Cruz 2015-12, Vol.110 (8), p.1010-1016
• Main Authors: Santana, Vinicius Canato, Almeida, Rafael Ribeiro, Ribeiro, Susan Pereira, Ferreira, Luís Carlos de Souza, Kalil, Jorge, Rosa, Daniela Santoro, Cunha-Neto, Edecio
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; AIDS Vaccines - immunology; Animals; Antigens, Viral - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cell Movement - drug effects; Cell Movement - immunology; Conserved Sequence - immunology; DNA vaccine; Enzyme-Linked Immunospot Assay; Female; Flow Cytometry; Genetic Vectors; granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; HIV; HIV Infections - prevention & control; HIV-1 - immunology; HLA-DR Antigens - immunology; Humans; Immunity, Cellular - immunology; Interferon-gamma - drug effects; Interferon-gamma - metabolism; Interleukin-2 - metabolism; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Mice, Inbred BALB C; PARASITOLOGY; Plasmids; polyfunctional CD4+ T-cells; Protein Binding - immunology; TROPICAL MEDICINE; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - metabolism; Vaccines, DNA - immunology
• ISSN: 0074-0276; 1678-8060; 1678-8060
• DOI: 10.1590/0074-02760150283

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.