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

Deborah Heydenburg Fuller, Laura Simpson, Kelly Stefano Cole, Janice E. Clements, Dennis L. Panicali, Ronald C. Montelaro, Michael Murphey-Corb, Joel R. Haynes

Research output: Contribution to journalReview articlepeer-review

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 SIV(mac239) 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 SIV(mac251) 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 SIV(Delta/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.

Original languageEnglish (US)
Pages (from-to)389-396
Number of pages8
JournalImmunology and Cell Biology
Volume75
Issue number4
DOIs
StatePublished - Jan 1 1997

Keywords

  • Gene gun
  • Nucleic acid immunization
  • Recombinant vaccinia virus
  • Rhesus macaque
  • SIV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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