This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Vaccine constructs consisting of plasmid DNA and HSVd106 vectors expressing SIV Gag, Env and a Rev-Tat-Nef fusion protein, were administered via the intramuscular route to 30 herpes B virus negative rhesus macaques at 0 and 4 weeks (primary inoculations), and at 12 and 24 weeks (booster inoculations). Six macaques each were assigned to receive a DNA prime-DNA boost, DNA prime-HSV boost, HSV prime-DNA boost, or a HSV prime-HSV boost immunization regimen. Six macaques received control HSVd106 empty vector. Macaques were challenged at week 36 with 3000 TCID50 of SIVmac239 administered via the intrarectal route.All four vaccination regimens induced persistent SIV-specific IFN-gamma and IL-2 ELISPOT responses in the peripheral blood, and tetramer-positive CD8+ T lymphocytes in the rectal mucosa and bronchoalveolar lavage. The highest magnitude of IFN-gamma ELISPOT responses were induced in the DNA prime-HSV boost group of vaccinated macaques, one week after HSV booster inoculation. HSV-primed macaques had lower magnitude of IFN-gamma ELISPOT responses compared to the DNA-primed animals, but the response quality was different. SIV-specific T lymphocytes secreting perforin, and with a balanced IFN-gamma- and IL-2-secreting profile were induced only after HSV priming. Additionally, ELISPOT responses in the peripheral lymph nodes, and neutralizing antibodies to lab-adapted SIVmac251 were predominantly observed only after HSVd106 immunization. Following SIVmac239 challenge viremia levels at 12 weeks were 15- to 44-fold lower in the vaccinated macaques compared to the control macaques. These results support the continued evaluation of recombinant HSV vectors as a promising candidate AIDS vaccine.
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