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 that cause (AIDS). In this study, six cynomolgus macaques were inoculated intrarectally with subinfectious or infectious doses of SIVsm to assess the SIV specific immunity, in particular protective immunity against subsequent challenge with a higher dose of SIVsm. Following the first inoculation with SIVsm, the two monkeys given the highest doses of cell-free SIVsm stock and one monkey given the intermediate dose became infected. In the three remaining animals, one animal inoculated with an intermediate dose and two animals given low doses of SIVsm, no overt infection occurred. Nevertheless, SIV specific cytotoxic T-cells against Gag/Pol and Nef proteins and T-cell proliferative responses against HIV-2 whole viral lysate, native HIV-2 gp125, recombinant SIV gp140 and SIV Env synthetic peptides were detected. After intrarectal rechallenge of the uninfected macaques with a higher dose of SIVsm all the animals became infected. These results demonstrate that cell mediated immunity can occur in the absence of detectable infection in monkeys inoculated with a low dose of SIVsm. Despite the presence of cellular immune responses, the animals were not protected when challenged with a higher dose of virus later.
Swedish Institute for Infectious Disease Control and Microbiology Tumour Biology Center, Karolinska Institute, SE-171 82, Solna, Sweden. barbro.makitalo@smi.ki.se
B
B
Mäkitalo
P
P
Böttiger1
G
G
Biberfeld
R
R
Thorstensson
D000285:Administration, Rectal; D000818:Animals; D018928:Immunity, Mucosal; D008213:Lymphocyte Activation; D008252:Macaca fascicularis; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*