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 w ith attenuated SIVmac1A11 results in transient viremia, anti-SIV antib ody responses, weak or absent cytotoxic T-lymphocyte responses, and no clinical disease. In light of these results, we hypothesized that con genital infection with SIVmac1A11 produced immune tolerance to SIV. To test this hypothesis, at approximately 1 year of age, five rhesus mac aques infected with SIVmac1A11 as fetuses (n = 3) or newborns (n = 2) and five naive juvenile rhesus macaques were challenged orally with pa thogenic SIVmac251. The five naive animals became persistently viremic after oral SIVmac251 inoculation. In contrast, one of three monkeys i noculated with SIVmac1A11 in utero and one of two animals inoculated w ith SIVmac1A11 at birth were virus culture negative. Virus was isolate d from PBMC of the other animals infected with SIVmac1A11 in utero or at birth. However, one animal had a substantially lower viral load tha n the control animals. These results suggest that SIV-specific immunit y rather than tolerance results from congenital infection with attenua ted SIVmac and that this immunity is sufficient to provide some protec tion from pathogenic virus challenge. These results also demonstrate t hat SIV can be transmitted orally in 6- to 17-month-old rhesus monkeys . (C) 1996 Academic Press, Inc.