Cell-mediated immunity to low doses of SIVsm in cynomolgus macaques did not confer protection against mucosal rechallenge

Simian immunodeficiency virus (SIV) infection of macaques is a useful model for studies of the roles of different immune responses against viruses tha t cause (AIDS). In this study, six cynomolgus macaques were inoculated intr arectally with subinfectious or infectious doses of SIVsm to assess the SIV specific immunity, in particular protective immunity against subsequent ch allenge with a higher dose of SIVsm. Following the first inoculation with S IVsm, the two monkeys given the highest doses of cell-free SIVsm stock and one monkey given the intermediate dose became infected. In the three remain ing animals, one animal inoculated with an intermediate dose and two animal s given low doses of SIVsm, no overt infection occurred. Nevertheless. SIV specific cytotoxic T-cells against Gag/Pol and Nef proteins and T-cell prol iferative responses against HIV-2 whole viral lysate, native HIV-2 gp125, r ecombinant SIV gp140 and SIV Env synthetic peptides were detected. After in trarectal rechallenge of the uninfected macaques with a higher dose of SIVs m all the animals became infected. These results demonstrate that cell medi ated immunity can occur in the absence of detectable infection in monkeys i noculated with a low dose of SIVsm. Despite the presence of cellular immune responses, the animals were not protected when challenged with a higher do se of virus later. (C) 2000 Elsevier Science Ltd. All rights reserved.