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. Passive transfer of neutralising antibodies failed to protect against challenge. The induction of SIV-specific cytotoxic T lymphocytes (CTLs) using lipopeptides also failed to protect from infection, and whereas the frequency of post-infection CTLs (as measured by limiting dilution CTL assay and MHC/tetramer staining) correlated inversely with the cell-associated virus load, no correlation with the plasma virus load was observed. No immunological correlation of protection could be identified in macaques immunised with live attenuated SIV, with sterilising immunity being induced as early as 10 weeks after infection with the attenuated virus. Similarly, whole inactivated virus and passive IgG transfer failed to protect the natural host AGM species from challenge with apathogenic SIVagm, although live attenuated SIVagm afforded some protection despite the lack of overt vaccine virus replication. Conclusions: ‘Traditional’ types of vaccine are either ineffective or inappropriate for use in humans. Current efforts are therefore focusing on the rapidly evolving field of genetic vaccines based on vector DNA and recombinant, attenuated viral and bacterial vectors.