Fetal or neonatal infection with attenuated simian immunodeficiency virus results in protective immunity against oral challenge with pathogenic SIVmac251

We have reported that infection of fetal or neonatal rhesus macaques with attenuated SIVmac1A11 results in transient viremia, anti-SIV antibody responses, weak or absent cytotoxic T-lymphocyte responses, and no clinical disease. In light of these results, we hypothesized that congenital infection with SIVmac1A11 produced immune tolerance to SIV. To test this hypothesis, at approximately 1 year of age, five rhesus macaques infected with SIVmac1A11 as fetuses (n = 3) or newborns (n = 2) and five naive juvenile rhesus macaques were challenged orally with pathogenic SIVmac251. The five naive animals became persistently viremic after oral SIVmac251 inoculation. In contrast, one of three monkeys inoculated with SIVmac1A11 in utero and one of two animals inoculated with SIVmac1A11 at birth were virus culture negative. Virus was isolated from PBMC of the other animals infected with SIVmac1A11 in utero or at birth. However, one animal had a substantially lower viral load than the control animals. These results suggest that SIV-specific immunity rather than tolerance results from congenital infection with attenuated SIVmac and that this immunity is sufficient to provide some protection from pathogenic virus challenge. These results also demonstrate that SIV can be transmitted orally in 6- to 17-month-old rhesus monkeys.