Comparative ability of various plasmid-based cytokines and chemokines to adjuvant the activity of HIV plasmid DNA vaccines

• Published in: Vaccine 2008-09, Vol.26 (37), p.4819-4829
• Main Authors: Xu, Rong, Megati, Shakuntala, Roopchand, Vidia, Luckay, Amara, Masood, Amjed, Garcia-Hand, Dorys, Rosati, Margherita, Weiner, David B, Felber, Barbara K, Pavlakis, George N, Sidhu, Maninder K, Eldridge, John H, Egan, Michael A
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - genetics; Adjuvants, Immunologic - pharmacology; AIDS Vaccines - immunology; Allergy and Immunology; Amino acids; Animals; Antigens; Applied microbiology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Chemokine; Chemokines; Cytokine; Cytokines; Cytomegalovirus; Deoxyribonucleic acid; DNA; env Gene Products, Human Immunodeficiency Virus - genetics; env Gene Products, Human Immunodeficiency Virus - immunology; Female; Flow cytometry; Fundamental and applied biological sciences. Psychology; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - immunology; Gene expression; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Growth hormones; HIV; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Immune response; Immune system; Immunization; Infections; Interleukin-12 - genetics; Interleukin-12 - pharmacology; Kinases; Ligands; Lymphocytes; Macaca; Membrane Proteins - genetics; Membrane Proteins - pharmacology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Molecular adjuvant; Plasmid DNA; Plasmids; Proteins; Signal transduction; T cell receptors; tat Gene Products, Human Immunodeficiency Virus - genetics; tat Gene Products, Human Immunodeficiency Virus - immunology; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - immunology; Vaccinia virus; Viral infections; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.06.103

Abstract The effectiveness of plasmid DNA (pDNA) vaccines can be improved by the co-delivery of plasmid-encoded molecular adjuvants. We evaluated pDNAs encoding GM-CSF, Flt-3L, IL-12 alone, or in combination, for their relative ability to serve as adjuvants to augment humoral and cell-mediated immune responses elicited by prototype pDNA vaccines. In Balb/c mice we found that co-administration of plasmid-based murine GM-CSF (pmGM-CSF), murine Flt-3L (pmFlt-3L) or murine IL-12 (pmIL-12) could markedly enhance the cell-mediated immune response elicited by an HIV-1 env pDNA vaccine. Plasmid mGM-CSF also augmented the immune response elicited by DNA vaccines expressing HIV-1 Gag and Nef-Tat-Vif. In addition, the use of pmGM-CSF as a vaccine adjuvant appeared to markedly increase antigen-specific proliferative responses and improved the quality of the resulting T-cell response by increasing the percentage of polyfunctional memory CD8+ T cells. Co-delivery of pmFlt-3L with pmGM-CSF did not result in a further increase in adjuvant activity. However, the co-administration of pmGM-CSF with pmIL-12 did significantly enhance env-specific proliferative responses and vaccine efficacy in the murine vaccinia virus challenge model relative to mice immunized with the env pDNA vaccine adjuvanted with either pmGM-CSF or pmIL-12 alone. These data support the testing of pmGM-CSF and pmIL-12, used alone or in combination, as plasmid DNA vaccine adjuvants in future macaque challenge studies.