期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：48
DOI：10.1073/pnas.2107832118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Nearly half of all pregnancies in the United States are unintended due to millions of women avoiding available hormonal contraceptive methods as a result of real and/or perceived side effects associated with the use of exogenous hormones. Topical vaginal delivery of antisperm monoclonal antibodies that could agglutinate sperm into clusters too large to penetrate mucus and prevent sperm from reaching the egg represents a potentially safe and potent mechanism for nonhormonal contraception. We report here the engineering of a vaginal film loaded with hexavalent (i.e., 6 Fab) antisperm IgG, made using GMP manufacturing processes, that possesses significantly superior agglutination potency than the parent IgG, enabling potent on-demand nonhormonal contraception via effectively agglutinating all human sperm within minutes.
Nonhormonal products for on-demand contraception are a global health technology gap; this unmet need motivated us to pursue the use of sperm-binding monoclonal antibodies to enable effective on-demand contraception. Here, using the cGMP-compliant
Nicotiana-expression system, we produced an ultrapotent sperm-binding IgG antibody possessing 6 Fab arms per molecule that bind a well-established contraceptive antigen target, CD52g. We term this hexavalent antibody “Fab-IgG-Fab” (FIF). The
Nicotiana-produced FIF had at least 10-fold greater sperm-agglutination potency and kinetics than the parent IgG, while preserving Fc-mediated trapping of individual spermatozoa in mucus. We formulated the
Nicotiana-produced FIF into a polyvinyl alcohol–based water-soluble contraceptive film and evaluated its potency in reducing progressively motile sperm in the sheep vagina. Two minutes after vaginal instillation of human semen, no progressively motile sperm were recovered from the vaginas of sheep receiving FIF Film. Our work supports the potential of multivalent contraceptive antibodies to provide safe, effective, on-demand nonhormonal contraception.
