The goal of Project 3 is to determine whether Human Contraception Antibody (HCA) binds to and neutralizes STI pathogens in semen. The rationale behind these experiments is our observation that the male reproductive tract restricted antigen CD52g, which is the target of HCA. inserts via GPI anchor into the plasma membrane of leukocytes and parasites in semen. We hypothesize that HCA will bind to and neutralize HIV infected cells in semen, as well as enveloped viruses that pick up CD52g from infected CD52g-coated cells in the male genital tract. Results of these studies will demonstrate whether HCA has dual activity as a contraceptive agent and STI microbicide.
Our Specific Aims are: 1. Determine whether CD52g attaches to seminal leukocytes, STI viruses (HIV-1, HSV-2 and ZIKV) and Trichomonas vaginalis. 2. Determine whether HCA binds to HIV-infected seminal leukocytes, STI viruses and Trichomonas vaginalis. and inhibits their ability to infect target cells. 3. Determine whether seminal leukocytes, viruses and parasites that are coated with CD52g agglutinate with each other or with sperm after treatment with HCA. 4. Determine whether HCA and engineered variants of HCA trap CD52g-coated leukocytes, STI viruses and parasites in cervical mucus (collaboration with Project 2)
We seek to develop a novel multipurpose prevention technology (MPT) platform based on human monoclonal antibodies (mAbs) to provide contraception and prevent sexually transmitted infections (STIs). We have identified a male-reproductive tract-specific antigen, CD52g, that is present on both sperm and STI pathogens in semen. This project will focus on the engineering of novel constructs of anti-CD52g mAbs, and their testing against a panel of STI pathogens and infected cells in semen.