title: Comparative ability of various plasmid-based cytokines and chemokines to adjuvant the activity of HIV plasmid DNA vaccines.
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.
authors.affiliation: Wyeth Vaccines Research, Pearl River, NY 10992, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Shakuntala
authors.initials: S
authors.lastname: Megati
authors.forename: Vidia
authors.initials: V
authors.lastname: Roopchand
authors.forename: Amara
authors.initials: A
authors.lastname: Luckay
authors.forename: Amjed
authors.initials: A
authors.lastname: Masood
authors.forename: Dorys
authors.initials: D
authors.lastname: Garcia-Hand
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Maninder K
authors.initials: MK
authors.lastname: Sidhu
authors.forename: John H
authors.initials: JH
authors.lastname: Eldridge
authors.forename: Michael A
authors.initials: MA
authors.lastname: Egan
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D019444:Vaccines, DNA / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D008565:Membrane Proteins; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C084881:flt3 ligand protein; D054301:gag Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor