• INFLUENZA
• HIV/SIV
• SARS

HIV/SIV

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 work with the Simian Vaccine Evaluation Unit at the WaNPRC to use macaque-specific oligonucleotide microarrays to analyze blood or tissue samples obtained from macaques in AIDS vaccine studies. Recent studies include genomic analyses of rhesus macaques infected with an SIV DNA vaccine (Belisle et al.) or with replicating adenovirus type 5 host range recombinant viruses (Palermo et al.).

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

Genomic and proteomic profiling is also being used to study SIV pathogenesis, including the host response during the actute phase of mucosal infection. Studies of HIV have demonstrated that the virus becomes compartmentalized during the course of infection, and our analysis of blood, lymph node, and gut-associated lymphoid tissues are providing insight into the behavior of the virus and the host response to infection mounted in these tissues.

We have also used gene expression profiling to examine acute SIV infection in pigtailed macaques and African green monkeys (Lederer et al.). Lentiviral infections lead to a broad range of outcomes in various primate species, and the same SIV strain that grows innocuously in African green monkeys will cause disease when introduced into pigtailed macaques. Our studies showed a loss of balance between Th17 and T regulatory cells in pigtailed macaques and tissue- and time-dependent transcriptional signatures that differentiated pathogenic and nonpathogenic infection. In particular, we observed that pigtailed macaques exhibited a strong and sustained type I IFN response, whereas in African green monkeys an initially strong IFN response resolved after peak viral load.