title: A dose sparing effect by plasmid encoded IL-12 adjuvant on a SIVgag-plasmid DNA vaccine in rhesus macaques.
abstract: An experimental pDNA vaccine adjuvant expressing IL-12 was evaluated for its ability to augment the humoral and cellular immune responses elicited by a SIVmac239 gag p39 expressing pDNA vaccine. To determine the effect of vaccine dose on the immune response, rhesus macaques were immunized with 1.5 mg or 5.0 mg of SIVmac239 gag pDNA, with or without co-immunization of IL-12 pDNA at 1.5 mg and 5.0 mg, respectively. Serum antibody responses to simian immunodeficiency virus (SIV) gag were increased 10-fold (p=0.044, 0.002) in macaques receiving IL-12 pDNA. Cellular immune responses, monitored by SIV gag-specific IFN-gamma ELISpot assay, were also significantly higher (p=0.007, 0.019) when the pDNA vaccine was co-immunized with IL-12 pDNA at high and low doses. There was no statistical difference between the immune responses elicited by the high and low dose of IL-12 pDNA (p=0.221, 0.917), a finding which could allow a dose reduction of vaccine without the concomitant loss of imunogenicity. Furthermore, analysis of the breadth of the T-cell response during the vaccination schedule, using overlapping peptides to SIV gag, demonstrated a significant correlation (p=0.0002) between the magnitude and breadth of the immune responses in the vaccines. These results have important implications for the continuing development of an effective, safe low dose pDNA vaccine adjuvant suitable for human use.
authors.affiliation: Wyeth Vaccines Research, Pearl River, NY 10965, USA.
authors.forename: Eva B
authors.initials: EB
authors.lastname: Schadeck
authors.forename: Maninder
authors.initials: M
authors.lastname: Sidhu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Egan
authors.forename: Siew-Yen
authors.initials: SY
authors.lastname: Chong
authors.forename: Priscilla
authors.initials: P
authors.lastname: Piacente
authors.forename: Amjed
authors.initials: A
authors.lastname: Masood
authors.forename: Dorys
authors.initials: D
authors.lastname: Garcia-Hand
authors.forename: Sarah
authors.initials: S
authors.lastname: Cappello
authors.forename: Vidia
authors.initials: V
authors.lastname: Roopchand
authors.forename: Shakuntala
authors.initials: S
authors.lastname: Megati
authors.forename: Jorge
authors.initials: J
authors.lastname: Quiroz
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.forename: John H
authors.initials: JH
authors.lastname: Eldridge
authors.forename: Zimra R
authors.initials: ZR
authors.lastname: Israel
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D015683:Gene Products, gag / Q000235:genetics*; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000235:genetics / Q000494:pharmacology*; D008253:Macaca mulatta; D010957:Plasmids; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D015683:Gene Products, gag; D019444:Vaccines, DNA; D018664:Interleukin-12