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

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 gpl20 and gpl60 (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 mac251gpl60 (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 DNA+VAC and VAC+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.