Grant: Project Grant

The increasing world population and escalating rates of sexually transmitted infections (STI) have prompted the WHO to promote the development of MPT (multipurpose prevention technology), which involves applying into the vagina single compounds/devices that simultaneously inhibit pregnancy and kill the bacteria and viruses that cause STI. Recently, we have shown that a human antimicrobial peptide, LL-37, which is secreted as part of innate immunity to fight against microbial pathogens, can act as a spermicide against both human and mouse sperm and by injecting LL-37 along with sperm into the mouse uterus, these mice fail to become pregnant. A shorter form of LL-37, GF-17 (half the size of LL-37 and thus less expensive to be made), also exerts the same spermicidal and microbicidal activities as LL-37. Our pilot study also shows anti-HIV effects of LL-37. However, LL-37 and GF-17 are prone to be broken down by enzymes in cervical-vaginal fluids (CVF). Therefore, we have started to work with a modified form of GF-17, called 17BIPHE2, which is much more resistant to CVF-induced degradation. Our results indicate the same contraceptive efficacy of 17BIPHE2 as LL-37/GF-17. Herein we propose to determine whether 1) multiple administration of LL-37/17BIPHE2 does not cause injury to the female reproductive tract (FRT) or decrease good microbes in the vagina, and the treated females can resume fecundity after cessation of the peptide treatments; 2) LL-37/17BIPHE2 inhibits HIV infection on host target cells in the FRT. 3) We will develop "nanoparticle (NP)" forms containing LL-37/17BIPHE2 for optimal delivery with a controlled rate of peptide release, following placement of these NPs into the vagina. The MPT efficacy of LL-37/17BIPHE2 will provide women with empowerment to protect themselves against unwanted pregnancies and STI.