title: Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid.
abstract: The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-gamma-producing CD8(+) and CD4(+) effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-gamma was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, 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: Gordon
authors.initials: G
authors.lastname: Vansant
authors.forename: David A
authors.initials: DA
authors.lastname: Hokey
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Rose
authors.initials: R
authors.lastname: Parkinson
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.forename: Maninder K
authors.initials: MK
authors.lastname: Sidhu
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: Charles
authors.initials: C
authors.lastname: Brown
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Joseph
authors.initials: J
authors.lastname: Monforte
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: John
authors.initials: J
authors.lastname: Eldridge
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D015683:Gene Products, gag / Q000276:immunology; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008251:Macaca / Q000276:immunology*; D010957:Plasmids / Q000235:genetics*; D012191:Retroviridae Proteins / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014779:Virus Replication
chemical_list: D015683:Gene Products, gag; D019409:Interleukin-15; D012191:Retroviridae Proteins; D007371:Interferon-gamma