Grant: Operating Grant - PA: Bridge Funding -CHVI Vaccine Discovery and Social Research

Currently, >25 million people have died of HIV/AIDS and 34 million are living with HIV/AIDS in the world. Medications have improved the quality of life and life expectancy of HIV-infected. However, for each person getting treatment, 2 or 3 become newly infected. A safe, effective and affordable vaccine is the only way to prevent new infections, save resources for prevention and treatment, and get control of the HIV epidemic. However, the normal vaccine approach has not worked for the HIV, which infects key cells in the immune system (the CD4 T cells) and new approaches are needed to develop a vaccine to prevent HIV infection. There are sex workers in Kenya who have been exposed to HIV but did not become infected. The information we learned from these people leads us to propose that an effective HIV vaccine should target key places in HIV instead of targeting the full HIV proteins. We have identified these key places as the sites where HIV generates infectious viral particles, the protease cleavage sites(PCS). The PCS are important because the enzyme that cuts proteins for the HIV virus, the protease, is responsible to produce HIV particles that can infect people. The protease has to bind 12 specific places in the HIV virus and conduct 12 separate cutting reactions to generate an infectious virus. If it can't bind to these places, the virus generated cannot infect the CD4 T cells. A vaccine that targets the 12 PCS could generate immune responses to force the virus to change itself, which would change these special cutting sites to result in a virus that can't infect people. In this study, we will compare the effect of a vaccine targeting the PCS in the HIV virus to a vaccine targeting two special proteins. We will test the protection that the vaccine provides against HIV infection and disease progression using a model system that includes Cynomolgus macaques and SIVmac251, a virus that is similar to HIV. This vaccine could be effective to prevent HIV infection.