A nef-deleted SHIV-NM-3rN (SHIV-NI) was previously shown to be nonpathogenic and to induce protective immunity. In the present study, a SHIV-NI expressing human interferon-γ (SHIV-IFN-γ) was constructed and the effect of co-expression of IFN-γ on virus replication and immunopotentiation was investigated in macaques that were vaccinated with both viruses, by comparing cytokine responses during the first 4 weeks after vaccination. Peripheral blood mononuclear cells (PBMC) isolated from vaccinated macaques were stimulated with inactivated viral particles for 24 h, and the production of IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-γ was determined by ELISA and flow cytometry. All of the vaccinated macaques showed increases in cytokine production. However, the production of IFN-γ (Th1-type cytokine) was more rapidly induced by SHIV-IFN-γ vaccination, and IFN-γ-producing cells appeared to be still increasing at 4 weeks after vaccination, although the difference of virus replication during the time was not significant in contrast to in vitro replication in cultured PBMC. These results suggest that co-expression of IFN-γ with SHIV can modulate the antiviral immune responses into the Th1 type response, which would probably provide more protective immunity.
Archives of Virology – Springer Journals
Published: Apr 1, 2004
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