Topical use of monoclonal antibodies as a multipurpose prevention technology offering contraception and decreased transmission of HIV-1 and trichomonas vaginalis
OA Version
Citation
Abstract
New transgenic antibody production platforms enable cost-effective, rapid manufacturing of antibodies for clinical applications. Our lab is investigating a human monoclonal antibody, the Human Contraceptive Antibody (HCA), produced in Nicotiana benthamiana, as a candidate for a topical Multipurpose Prevention Technology offering both contraception and protection against sexually transmitted infections. HCA was developed from a sperm-agglutinating antibody isolated from plasma cells of an infertile woman. The antibody targets a GPI-anchored glycoprotein, CD52g, produced specifically by epithelial cells in the male reproductive tract (MRT). Due to its GPI anchor, the hypermobile protein coats sperm as they migrate through the MRT. In this study, we tested HCA’s specificity and contraceptive properties under physiologically relevant conditions in vitro. We demonstrated that HCA quickly and potently agglutinates sperm in physiological conditions at concentrations >6.25 μg/mL. Sperm concentration, soluble CD52g found in seminal plasma/whole semen, or prolonged exposure to the low pH found in the vaginal tract did not affect agglutination time. We also determined that CD52g incorporates into other cells present in the MRT, including human immunodeficiency virus (HIV-1) infected cells (lymphocytes, macrophages) and the parasite, Trichomonas vaginalis (TV), and that HIV virions produced from CD52g-coated cells incorporate CD52g in the virus particle membrane. HCA alone did not agglutinate HIV or TV. Both pathogens, however, appeared to co-agglutinate with sperm when co-cultures were treated with HCA. The trapping of pathogens in sperm agglutinates resulted in decreased TV adherence to MatTek tissue and vaginal epithelial cells, and a modest neutralization of HIV-1 in TZM-bl assays. These data indicate that HCA is a promising candidate to achieve contraception and decrease the male-to-female transmission of STI pathogens.