The role of nonhuman primates in the development of an AIDS vaccine

Over the past decade, a substantial research investment has generated a vast body of knowledge relevant to the development of an effective AIDS vaccine. Furthermore, studies in nonhuman primates have demonstrated that a number of candidate immunogens can confer a significant degree of protection against a potentially pathogenic SIV or SHIV. Currently, there exists a robust program that supports discovery of new HIV immunogens and a proven successful program for collaborative human trials of promising vaccine candidates. However, we believe that there is a gap between discovery and clinical trials. An orderly process for screening of candidate immunogens prior to human trials would facilitate the vaccine development program. We suggest that nonhuman primates can fill this strategic gap and could accelerate vaccine development. Recognizing that there is considerable controversy about the potential usefulness of the primate models, we have attempted to set forth the relevant practical and biological issues as a series of questions for discussion. The most important biological problem is the absence of a single immune response correlate that will predict vaccine efficacy. Data from primate models indicate that such a single predictive correlate may not exist. In turn, this argues for a vaccine screening protocol that includes a pathogenic virus challenge, an approach only available in the nonhuman primate model. The further assumption is that nonprimate models can be used to predict the relative protective efficacy of diverse immunization protocols, a hypothesis that can only be tested by comparative studies yet to be conducted. A 'standard' set of virus challenges must be selected for comparison of different immunization protocols, and this effort has been initiated. At the practical level, it appears that the large number of candidate immunogens now being developed requires a screening process of the kind proposed, since it would not be practical to test all new immunogens and protocols in humans. In conclusion, it appears timely to crystallize an orderly process for the discovery, screening, and human testing of candidate AIDS vaccines, understanding that a vaccine development program should not be conducted at the expense of investigator-initiated research in the diverse disciplines that support rational vaccine design and development. The components of a rational process of vaccine development are well established and only remain to be welded into one coherent program.