A MINIMALLY REPLICATIVE HIV-2 LIVE-VIRUS VACCINE PROTECTS MACACA-NEMESTRINA FROM DISEASE AFTER HIV-2(287) CHALLENGE

M. nemestrina immunized with an apathogenic HIV-2 molecular clone (HIV -2(KR)) were protected from CD4 decline and disease upon challenge wit h HIV-2(287), after any immunizing virus could be detected. Higher but not lower inocula of HIV-2(KR) were protective against intravenous in oculation of either 10(5) or 10(1) TCID50 of HIV-2(287). Protected ani mals displayed substantial reductions in PBMC proviral burden (1-3 log s), viral titers (1-2 logs), and plasma viral RNA (2-4 logs) compared to unprotected or naive animals as early as 1 week postinfection. Plas ma viral RNA became undetectable after 24 weeks in protected animals, but remained high in unprotected animals, No viral RNA was present in the spleen of the protected animal necropsied more than a year after c hallenge (though viral DNA was still present). No neutralizing respons es could be demonstrated, but CTL activity was detected sooner and at higher levels after challenge in protected than in unprotected macaque s. In this novel HIV-2 vaccine model, protection was clearly dose-depe ndent, and clearance of challenge virus RNA from the plasma did not re quire detectable ongoing replication of the immunizing virus at the ti me of challenge, (C) 1998 Academic Press.