PMID- 26602876 OWN - NLM STAT- MEDLINE DCOM- 20160601 LR - 20181113 IS - 1678-8060 (Electronic) IS - 0074-0276 (Print) IS - 0074-0276 (Linking) VI - 110 IP - 8 DP - 2015 Dec TI - Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses. PG - 1010-6 LID - S0074-02762015005025104 [pii] LID - 10.1590/0074-02760150283 [doi] AB - 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-gamma, tumour necrosis factor-alpha 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. FAU - Santana, Vinicius Canato AU - Santana VC AD - Divisao de Imunologia Clinica e Alergia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil. FAU - Almeida, Rafael Ribeiro AU - Almeida RR AD - Divisao de Imunologia Clinica e Alergia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil. FAU - Ribeiro, Susan Pereira AU - Ribeiro SP AD - Divisao de Imunologia Clinica e Alergia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil. FAU - Ferreira, Luis Carlos de Souza AU - Ferreira LC AD - Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, SP, Brasil. FAU - Kalil, Jorge AU - Kalil J AD - Instituto de Investigacao em Imunologia, Instituto Nacional de Ciencia e Tecnologia, Sao Paulo, SP, Brasil. FAU - Rosa, Daniela Santoro AU - Rosa DS AD - Instituto de Investigacao em Imunologia, Instituto Nacional de Ciencia e Tecnologia, Sao Paulo, SP, Brasil. FAU - Cunha-Neto, Edecio AU - Cunha-Neto E AD - Divisao de Imunologia Clinica e Alergia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151124 PL - Brazil TA - Mem Inst Oswaldo Cruz JT - Memorias do Instituto Oswaldo Cruz JID - 7502619 RN - 0 (AIDS Vaccines) RN - 0 (Adjuvants, Immunologic) RN - 0 (Antigens, Viral) RN - 0 (HLA-DR Antigens) RN - 0 (Interleukin-2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vaccines, DNA) RN - 82115-62-6 (Interferon-gamma) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - AIDS Vaccines/*immunology MH - Adjuvants, Immunologic/administration & dosage MH - Animals MH - Antigens, Viral/*immunology MH - CD4-Positive T-Lymphocytes/drug effects/*immunology MH - Cell Movement/drug effects/immunology MH - Conserved Sequence/immunology MH - Enzyme-Linked Immunospot Assay MH - Female MH - Flow Cytometry MH - Genetic Vectors MH - Granulocyte-Macrophage Colony-Stimulating Factor/*administration & dosage/immunology MH - HIV Infections/prevention & control MH - HIV-1/*immunology MH - HLA-DR Antigens/immunology MH - Humans MH - Immunity, Cellular/*immunology MH - Interferon-gamma/drug effects/metabolism MH - Interleukin-2/metabolism MH - Lymphocyte Activation/drug effects/immunology MH - Mice, Inbred BALB C MH - Plasmids MH - Protein Binding/immunology MH - Tumor Necrosis Factor-alpha/drug effects/metabolism MH - Vaccines, DNA/*immunology PMC - PMC4708021 EDAT- 2015/11/26 06:00 MHDA- 2016/06/02 06:00 PMCR- 2015/12/01 CRDT- 2015/11/26 06:00 PHST- 2015/07/29 00:00 [received] PHST- 2015/10/20 00:00 [accepted] PHST- 2015/11/26 06:00 [entrez] PHST- 2015/11/26 06:00 [pubmed] PHST- 2016/06/02 06:00 [medline] PHST- 2015/12/01 00:00 [pmc-release] AID - S0074-02762015005025104 [pii] AID - 10.1590/0074-02760150283 [doi] PST - ppublish SO - Mem Inst Oswaldo Cruz. 2015 Dec;110(8):1010-6. doi: 10.1590/0074-02760150283. Epub 2015 Nov 24.