HIV/SIV MODEL
Vaccine evaluation
Macaques are the only animal model that suitably emulates the process of HIV infection and disease progression to AIDS. These animals are essential for the development and evaluation of AIDS vaccine strategies, and genomic technologies can significantly aid in the vaccine evaluation process. We are working with Dr. Marjorie Robert-Guroff (National Cancer Institute) to use macaque-specific oligonucleotide microarrays to analyze blood samples obtained from macaques in an ongoing vaccine study aimed at evaluating immunization regimens based on replicating Ad-HIV/SIV recombinants with or without additional boosts of viral protein immunogens.
Microarray analyses are being conducted on blood samples taken prior to immunization, at multiple points during the immunization phase, and at multiple points following viral challenge. Gene expression changes associated with responding members of the vaccine groups will be compared with gene expression profiles of non-responders and control animals. Expression profiles will also be analyzed for features that correlate with innate or acquired immunity or with attenuation of disease. Our long-term goals include discovery of gene expression signatures that define successful vaccination and differentiate vaccine candidates in a qualitative fashion. These studies may lead to markers that highlight variation in the genetic makeup of naïve animals that make them more or less susceptible to infection, which in turn may lead to potential targets for future vaccine development.
Pathogenesis
Lentiviral infections lead to a broad range of outcomes in various primate species. For example, the same SIV strain that grows innocuously in African green monkeys will cause disease when introduced into pigtailed macaques. To better understand these diverse outcomes, we are collaborating with Dr. J.M. McCune (University of California, San Francisco) to use gene expression profiling to examine acute SIV infection in pigtailed macaques and African green monkeys. We anticipate that such profiling will provide information about which pathways of innate and adaptive immune activation are associated with pathogenic or nonpathogenic outcomes. Such information may be useful for developing therapeutic or vaccine strategies and may also be pertinent to understanding pathogenesis induced by other viruses in humans, such as hepatitis C virus with or without HIV co-infection.