Abrogation of attenuated lentivirus-induced protection in rhesus macaques by administration of depo-provera before intravaginal challenge with simian immunodeficiency virus mac239.

Abstract

In nonhuman primate models of acquired immunodeficiency syndrome, live attenuated lentiviruses provide the most reliable protection from systemic and mucosal challenge with pathogenic simian immunodeficiency virus (SIV). Although live attenuated lentiviruses may never be used in humans because of safety concerns, understanding the nature of the protective immune mechanisms induced by live attenuated vaccines in primate models will be useful for developing other vaccine approaches. Approximately 60% of rhesus macaques immunized with nonpathogenic simian-human immunodeficiency virus (SHIV) strain 89.6 are protected from infection or clinical disease after intravaginal (IVAG) challenge with pathogenic SIVmac239. The goal of the present study was to determine whether administration of Depo-Provera before IVAG challenge with SIV decreases the protective efficacy of infection with SHIV89.6. The rate of protection after IVAG challenge with SIVmac239 was significantly lower (P<.05), and the acute postchallenge plasma viral RNA levels were significantly higher (P<.006), in Depo-Provera-treated, SHIV89.6-immunized macaques than in Depo-Provera-naive, SHIV89.6-immunized macaques. In the primate model of sexual transmission of human immunodeficiency virus, treatment with progesterone before IVAG challenge with a pathogenic virus can decrease the efficacy of a model "vaccine."