PROTECTION AGAINST MUCOSAL SIVSM CHALLENGE IN MACAQUES INFECTED WITH A CHIMERIC SIV THAT EXPRESSES HIV TYPE-1 ENVELOPE

In a monkey model we used a chimeric SIV expressing the HIV-1 envelope gene (SHIV-4) as a live attenuated vaccine and a virulent SIVsm as a mucosal challenge, Four cynomolgus monkeys were inoculated intravenous ly with SHIV-4, Virus was repeatedly isolated from blood mononuclear c ells of all four animals for 2 to 7 months after the inoculation of SH IV, All monkeys developed neutralizing antibodies to HIV-1 and high an tibody titers to HIV-1 envelope glycoproteins. III contrast, no neutra lizing antibodies to SIVsm were detected and cross-reacting antibodies to SIV envelope glycoproteins were demonstrable in low titers, Nine t o 12 months after the SHIV inoculation the four monkeys and six naive control monkeys were challenged intrarectally with 10 monkey infectiou s doses of macaque cell-grown SIVsm. After a follow-up period of 1 yea r, two of four SHIV-infected monkeys were completely protected against SIVsm infection as shown by repeated negative virus isolations and ne gative polymerase chain reaction for SIV envelope DNA, One naive monke y that received blood from the two protected monkeys showed no signs o f infection, The remaining two SHIV-infected monkeys showed an initial infection on challenge with SIVsm, but viral replication was thereaft er suppressed. Cytotoxic T lymphocytes to SIV Nef and RT were demonstr able in one of four SHIV-infected monkeys before SIVsm challenge, but this monkey was not protected against SN infection, All six control an imals yielded virus repeatedly after SIVsm challenge and three of them showed declining CD4 cell counts, Thus, infection with SHIV expressin g HIV-1 envelope could induce cross-protection against mucosal SIVsm c hallenge.