Conformationally-intact inactivated SIV virions as an antigen to monitor specific proliferative responses to SIV

Recent studies of HIV infected patients have underscored the association of strong proliferative responses to HIV antigens with a favorable clinical course. However, little is known about the development of these responses in primary infection. SIV infection of macaques is an excellent way to study primary retroviral infection, but until recently, available antigens have not allowed reliable measurements of SIV-specific proliferative responses. We used a novel SIV antigen preparation to monitor the development of virus-specific proliferative responses during primary SIV infection. Tetanus immunized rhesus macaques received either high (2 X 10(4) monkey infectious doses MID; n=4) or low (2 X 10(1) MID; n=4) intravenous inocula of SIVmac239. In vitro lymphocyte responses were monitored using a [(3)H]-thymidine incorporation readout. Peripheral blood mononuclear cells were stimulated with mitogen (PHA), tetanus toxoid, or with inactivated, conformationally intact SIV virions, prepared by covalent modification of nucleocapsid protein zinc fingers (Rossio et al., J Virol, 1998). By 4 weeks post-inoculation, strong proliferative responses to SIV were seen in 3 of 4 animals receiving the high dose of SIV (SI 15.5 +/- 1.0). In the low-dose group, 2 of 4 animals showed good responses (SI 5.9 +/- 1.4), but peak responses were delayed 2 to 4 weeks compared to the animals that received the larger inoculum. All responding animals maintained their responses over an initial 8 week follow up period. Six of 8 animals boosted with tetanus toxoid on the day of virus challenge showed strong antigen-specific proliferation (SI 94.8 +/- 27.5), which subsided over the next 4 weeks. Follow-up continues; current results will be presented. Conformationally intact SIV virions inactivated by covalent modification of nucleocapsid protein zinc fingers may be a useful antigen for monitoring SIV immune responses in pathogenesis, antiretroviral treatment and vaccine studies. Contract No. N01-CO-56000.

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