Grant: Operating Grant

HIV infects over 40 million people worldwide, with over 60 million individuals infected or dead since the 1980's. HIV disproportionately infects women due to social and biological factors, and thus there has been an effort to develop female-controlled preventative technologies for women, such as vaginal microbicides. Such technologies would be extremely beneficial as it would give women the ability to protect themselves independent of partner consent, especially when partners do not wish to use condoms. However, a lack the knowledge of what provides natural protection from HIV infection in women has prevented progress in this area. Clues of what provides protection from HIV may come from studying a group of women Pumwani Sex Worker cohort in Kenya who have shown a natural protective immunity to HIV. Even after repeated exposures to HIV, from multiple infected sexual partners, they remain infection-free, some for more than 25 years. These 'HIV-resistant' individuals represent a model of protection and understanding their unique immune systems may provide us with information on how to design an effective microbicide. Our research has shown that HIV-resistant women secrete higher amounts of novel protein factors in their genital secretions, called Serpins. Serpins are known to be involved with host defense against bacteria/viruses and have shown direct anti-HIV activity, as well as have general anti-inflammatory capabilities, which is a known risk factor for infection in women. For these reasons we believe Serpins are contributing to natural protection against HIV-infection. We wish to study their biological function in the female genital tract with respect to HIV-infection. This proposal will further our understanding of their biological role against HIV-infection and may allow us to use them in a novel microbicide formulation. This may lead to the development of novel female-controlled protection technologies.