Vaccine development using the simian immunodeficiency virus model for AIDS.

Objective: A number of trials in primates using a wide range of putative vaccines based on simian immunodeficiency virus (SIV) have been performed and are summarised here.

Methods: Rhesus macaques and African green monkey (AGMs) were immunised with the test vaccines and challenged with live virus to test the efficacy of the induced or transferred immune responses to protect from infection or disease development.

Results: In initial studies, successful protection from challenge by whole inactivated virus vaccines was subsequently shown to be mediated by immune responses to human cell rather than viral proteins.

Simian immunodeficiency viruses with defective nef genes show increased susceptibility to the noncytotoxic antiviral activity of CD8+ lymphocytes.

The noncytotoxic soluble factor produced by CD8+ T cells inhibits replication of HIV and SIV in vitro and is thought to play a crucial role in combatting infection in vivo. We determined the effect of human CD8+ lymphocytes on the in vitro replication potential of both wild-type and nef-defective mutants of the simian immunodeficiency virus SIVmac251. Although replication of wild-type SIVmac251 in unstimulated human PBMC supplemented with IL-2 was unaffected by the presence of CD8+ T cells, the nef mutants were susceptible to the inhibitory effects.