Grant: Team Grant: Mucosal Immunology for HIV Vaccine Development

Women are disproportionately affected by HIV/AIDS, and represent more than half of the 2 million new infections each year. For this reason there is an urgent need for the development of better female-controlled prevention options. Within this context, interest has grown in the development of preventative technologies, such as vaginal microbicides or topical pre-exposure prophylaxis (PreP). These technologies would be extremely beneficial as it would provide women the ability to protect themselves independent of partner consent. Although recent microbicide clinical trials have shown partial protective effects by (39%), these are well below the threshold that would make them an effective large-scale prevention option. As microbicides are designed to prevent HIV from establishing an infection at the first site of contact in the genital tract mucosa, their efficacy is dependent upon our knowledge of what mucosal immune factors makes a woman susceptible to HIV infection. However, to date these processes are not well understood and are the greatest impediment to improving these technologies. Clues to understanding these processes is to study events that precede infection. Our preliminary research with a recent microbicide clinical trial has revealed that specific immune responses, related to hormone levels and the menstrual cycle, are strongly associated with risk of HIV infection in women. These progesterone-related factors enhance inflammation processes, which paradoxically may provide a favourable environment for HIV infection. This study proposes to further examine the association of these mucosal factors with female sex hormones, the menstrual cycle, and progesterone-based contraceptives with HIV susceptibility. Understanding this relationship may have important implications for new preventative technologies/vaccines, as well as hormonal contraceptive use for women at high risk for HIV infection.