A Minimally Replicative HIV-2 Live-Virus Vaccine ProtectsM. nemestrinafrom Disease after HIV-2287Challenge

Abstract

M. nemestrinaimmunized with an apathogenic HIV-2 molecular clone (HIV-2KR) were protected from CD4 decline and disease upon challenge with HIV-2287, after any immunizing virus could be detected. Higher but not lower inocula of HIV-2KRwere protective against intravenous inoculation of either 105or 101TCID50of HIV-2287. Protected animals displayed substantial reductions in PBMC proviral burden (1–3 logs), viral titers (1–2 logs), and plasma viral RNA (2–4 logs) compared to unprotected or naive animals as early as 1 week postinfection. Plasma 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 challenge (though viral DNA was still present). No neutralizing responses could be demonstrated, but CTL activity was detected sooner and at higher levels after challenge in protected than in unprotected macaques. In this novel HIV-2 vaccine model, protection was clearly dose-dependent, and clearance of challenge virus RNA from the plasma did not require detectable ongoing replication of the immunizing virus at the time of challenge.