title: Gene gun-based nucleic acid immunization alone or in combination with recombinant vaccinia vectors suppresses virus burden in rhesus macaques challenged with a heterologous SIV.
abstract: Gene gun-based DNA immunization alone or in combination with recombinant vaccinia vectors was evaluated for the ability to elicit protective immune responses in rhesus macaques challenged with a pathogenic, heterologous simian immunodeficiency virus (SIV). Six monkeys primed with seven consecutive doses of DNA encoding SIVmac239 gp120 and gp160 (DNA + DNA) were divided into two groups. Three of these animals received another DNA booster immunization and the remaining three received a booster immunization containing a homologous, live recombinant vaccinia virus expressing SIVmac251 gp160 (DNA + VAC). In addition, a group of 15 animals primed with recombinant vaccinia vectors were divided into two groups. One group of six monkeys received another immunization of vaccinia (VAC + VAC) and the other nine animals received a DNA (mac239) booster immunization (VAC + DNA). Geometric mean end-point IgG titres in the DNA + VAC and VAC + DNA groups were substantially higher than the responses seen in the VAC + VAC and DNA + DNA groups, demonstrating a synergistic relationship between DNA-based vaccines and recombinant vaccinia virus-based vaccines. All vaccinates and five naive controls were challenged 19 weeks after the final booster immunization with 10 animal infectious doses of SIVDelta/B670. The vaccines did not prevent infection. However, all vaccine groups showed significant virus load reductions from seven to 56 days post challenge when compared to controls. Although the DNA + DNA group developed the lowest prechallenge antibody responses, the most significant reduction (200-fold) in virus load was associated with this group. In addition, a significant delay in CD4+ T cell loss relative to controls was observed in the DNA + DNA group. These results demonstrate that a gene gun-based DNA vaccine provided some attenuation of infection and CD4+ T cell loss after a heterologous challenge.
authors.affiliation: Geniva, Middleton, Wisconsin, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Fuller
authors.forename: L
authors.initials: L
authors.lastname: Simpson
authors.forename: K S
authors.initials: KS
authors.lastname: Cole
authors.forename: J E
authors.initials: JE
authors.lastname: Clements
authors.forename: D L
authors.initials: DL
authors.lastname: Panicali
authors.forename: R C
authors.initials: RC
authors.lastname: Montelaro
authors.forename: M
authors.initials: M
authors.lastname: Murphey-Corb
authors.forename: J R
authors.initials: JR
authors.lastname: Haynes
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D007277:Injections, Jet; D008253:Macaca mulatta; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*; D014759:Viral Envelope Proteins; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; C087575:SIV envelope glycoprotein gp160; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus