GENE GUN-BASED NUCLEIC-ACID IMMUNIZATION ALONE OR IN COMBINATION WITHRECOMBINANT VACCINIA VECTORS SUPPRESSES VIRUS BURDEN IN RHESUS MACAQUES CHALLENGED WITH A HETEROLOGOUS SIV

Gene gun-based DNA immunization alone or in combination with recombina nt vaccinia vectors was evaluated for the ability to elicit protective immune responses in rhesus macaques challenged with a pathogenic, het erologous simian immunodeficiency virus (SIV). Six monkeys primed with seven consecutive doses of DNA encoding SIVmac239 gp120 and gp160 (DN A+DNA) were divided into two groups. Three of these animals received a nother DNA booster immunization and the remaining three received a boo ster immunization containing a homologous, live recombinant vaccinia v irus 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 vac cinia (VAC+VAC) and the other nine animals received a DNA (mac239) boo ster immunization (VAC+DNA). Geometric mean end-point IgG titres in th e DNA+VAC and VAC+DNA groups were substantially higher than the respon ses seen in the VAC+VAC and DNA+DNA groups, demonstrating a synergisti c relationship between DNA-based vaccines and recombinant vaccinia vir us-based vaccines. All vaccinates and five naive controls were challen ged 19 weeks after the final booster immunization with 10 animal infec tious doses of SIVDelta/B670. The vaccines did not prevent infection. However, all vaccine groups showed significant virus load reductions f rom seven to 56 days post challenge when compared to controls. Althoug h the DNA+DNA group developed the lowest prechallenge antibody respons es, the most significant reduction (200-fold) in virus load was associ ated with this group. In addition, a significant delay in CD4+ T cell loss relative to controls was observed in the DNA+DNA group. These res ults demonstrate that a gene gun-based DNA vaccine provided some atten uation of infection and CD4(+) T cell loss after a heterologous challe nge.