Expression of gamma interferon by simian immunodeficiency virus increases attenuation and reduces postchallenge virus load in vaccinated rhesus macaques

Simian immunodeficiency virus (SIV) infection of macaques is a model for human immunodeficiency virus (HIV) infection. We have previously reported the construction and characterization of an SIV vector with a deletion in the nef gene (SIVDelta nef) and expressing gamma interferon (SIVHyIFN) (L. Giavedoni and T. Yilma, J. Virol. 70:2247-2251, 1996). We now show that rhesus macaques vaccinated with SIVHyIFN have a lower viral load than a group similarly immunized with SIVDelta nef. Viral loads remained low in the SIVHyIFN-vaccinated group even though SIV expressing gamma interferon could not be isolated after 6 weeks postimmunization in these animals. All immunized and two naive control macaques became infected when challenged with virulent SIVmac251 at 25 weeks postvaccination. In contrast to the two naive controls that died by 12 and 18 weeks postchallenge, all vaccinated animals remained healthy for more than 32 weeks. In addition, postchallenge cell-associated virus load was significantly lower in SIVHyIFN-immunized animals than in the group vaccinated with SIVDelta nef. These findings indicate that cytokine-expressing viruses can provide a novel approach for development of safe and efficacious live attenuated vaccines for AIDS.