Grant: Operating Grant

The world population is exponentially increasing, and is expected to reach 9.1 billion in 2050. Concurrently, the worldwide spread of AIDS, caused by HIV, is rising at an alarming rate. With no cure, over 30 million people are currently living with AIDS, and approximately 1.5 million AIDS patients die annually. Women are more prone to contract AIDS through heterosexual intercourse, with their vaginal/cervical lining being the primary HIV infection site. For these reasons, it is desirable to have a vaginal contraceptive with anti-HIV properties, as it will empower women in both family planning and safe sexual practices. We have been exploring the use of antimicrobial peptides as contraceptives by examining their inhibitory actions on sperm fertilizing ability. Antimicrobial peptides are small, positively charged proteins that bind to negatively charged components on bacterial membranes, rupture them, and ultimately cause cell death. In an analogous manner, sperm membranes can be perforated by these peptides, due in part to the presence of a specific lipid on the sperm membrane that is also negatively charged. Interestingly, one such antimicrobial peptide, LL-37, is produced naturally in the vagina, 2-6 hours post-intercourse. Therefore, sperm never see LL-37, as they have already swum into the uterus. Our studies have revealed that the treatment of sperm with LL-37 at normal physiological levels leads to the loss of sperm fertilizing ability, and results in a complete lack of pregnancy in mouse models. LL-37 has also been reported to have anti-HIV properties, and could serve as both a vaginal contraceptive and anti-HIV agent. Our proposed studies are geared towards obtaining a better understanding of the contraceptive action of LL-37 and related shorter peptides (which are cheaper to manufacture), and their inhibitory effects on HIV infection.