New directions for HIV vaccine development from animal models

Abstract

The development of a preventive HIV vaccine remains an unresolved challenge. Animal models that can predict the results of HIV vaccine efficacy trials and identify the immune mechanisms responsible for vaccine protection would be most useful for HIV vaccine development. The purpose of the current review is to critique recent developments in the use of animal models of HIV infection in preclinical studies of AIDS vaccines and to describe how the use of improved animal models can inform the development of an HIV vaccine. The results of preclinical experiments with candidate HIV vaccines can vary with the SIV challenge virus used. It is now known that there is considerable variability in the neutralization sensitivity and that the level of viral sequence diversity within the challenge stocks varies. This has allowed more realistic preclinical vaccine studies with heterologous vaccine antigens and challenge viruses. Further, the dose of challenge virus and the route of virus challenge can modify the efficacy of candidate vaccines in preclinical studies. Recent experiments demonstrate that nonhuman primate models of AIDS can reproduce the complex biology of HIV transmission, recapitulate the results of HIV vaccine efficacy trials in humans and be used to identify correlates of protection.