Grant: Operating Grant - PA: Regional Partnership Program : Manitoba

HIV-1 infects over 40 million people worldwide, with over 60 million individuals infected or dead since the 1980's. Despite the enormous effort on preventative measures the pandemic continues to spread with more than 4 million new HIV-1 infections per year. It is widely accepted that the most effective means to turn the tide against this infectious disease is the development of a vaccine. However, even after more than two decades of HIV research we have not made any substantial progress in this area. The development of vaccines has traditionally been accomplished by studying individuals who have natural protective immunity. The vaccine for smallpox, for example, was discovered through the observation that milkmaids who had been previously exposed to cowpox were protected from the deadly smallpox virus. Therefore this understanding of what comprises protective immunity laid the foundation for the development of a vaccine. We are taking a similar approach in HIV/AIDS by studying exposed-uninfected individuals belonging to the Punwami Sex Worker cohort in Kenya who have shown a natural protective immunity to HIV-1. Our studies show that HIV-resistant women secrete novel protein factors in their genital mucosa, called Serpins. Serpins are known to be involved with host defense against bacteria/viruses and have shown direct anti-HIV activity. They also have general anti-inflammatory capability and inflammation is known to increase the risk of HIV-infection. For these reasons we believe these proteins are contributing to a protective environment against HIV-infection and we wish to understand their biological function in HIV transmission. Understanding their biological significance and mechanism of action may help in the development of preventative treatments and/or vaccines against HIV.