title: SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques.
abstract: Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV-1)-specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co-delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)-12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL-12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL-12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co-injected with the IL-12 molecular adjuvant. The IL-12 expanded antigen-specific IFN-gamma positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component. The adjuvanted DNA vaccines illustrate that IL-12 enhances a CD8 vaccine immune response, however, different cellular profiles.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
authors.forename: Tara M
authors.initials: TM
authors.lastname: Robinson
authors.forename: Michele A
authors.initials: MA
authors.lastname: Kutzler
authors.forename: R
authors.initials: R
authors.lastname: Parkinson
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Calarota
authors.forename: Maninder K
authors.initials: MK
authors.lastname: Sidhu
authors.forename: Karuppiah
authors.initials: K
authors.lastname: Muthumani
authors.forename: Mark
authors.initials: M
authors.lastname: Lewis
authors.forename: George
authors.initials: G
authors.lastname: Pavlakis
authors.forename: Barbara
authors.initials: B
authors.lastname: Felber
authors.forename: David
authors.initials: D
authors.lastname: Weiner
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D015683:Gene Products, gag / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008252:Macaca fascicularis; D008992:Monkey Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D010957:Plasmids / Q000276:immunology; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014162:Transfection / Q000662:veterinary
chemical_list: C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D018449:SAIDS Vaccines; D023201:CD40 Ligand; D018664:Interleukin-12