Preclinical primate studies of HIV-1-envelope-based vaccines: towards human clinical trials

There is growing debate on how nonhuman primate models of AIDS can best guide and facilitate clinical development of HIV vaccines. This review covers the simian/human immunodeficiency virus primate model and its strategic use in guiding the development and selection of HIV-1-envelope-based vaccine candidates to clinical trials.

There is a strong desire to have one clear 'immune correlate' of protection from HIV/AIDS to guide clinical vaccine development. This is unlikely to emerge, as immunity to HIV-1 is interdependent and very complex (i.e. quality versus quantity). Thus the problem can better be focused on the definition of the specific vaccine question being asked and the correct design of the preclinical study. Only now are head-to-head comparison studies being designed to directly compare immune responses in humans with those exact same vaccine candidates in rhesus monkeys.

Whereas T-cell-based vaccine candidates are being developed and advanced, the needs from the macaque model are for comparative immunogenicity and 'predictive outcomes' to refine and facilitate clinical trial design. With respect to neutralizing antibody (B-cell) vaccine strategies, the needs are currently at earlier discovery and proof-of-concept stages requiring HIV-1-envelope-based SHIV-challenges.