Abstract
Many women risk unintended pregnancy due to dissatisfaction with available hormonal contraceptive methods. This led us to pursue topical sperm-binding monoclonal antibodies as a strategy for safe, non-hormonal contraception. Motivated by the greater agglutination potencies of polymeric immunoglobulins such as IgM and the exceptional bioprocessing ease in manufacturing IgG, we engineered IgGs possessing 6-10 Fabs against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) are at least 10- to 16-fold more potent and faster than the parent IgG at agglutinating sperm, while preserving Fc-mediated trapping of individual spermatozoa in mucus. The increased potencies translate to effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using 33 micrograms of the 10 Fab HM-IgG. HM-IgGs produce at comparable yields and possess identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for non-hormonal contraception but also a promising platform for generating potent agglutinating mAb for diverse medical applications.
Competing Interest Statement
S.K.L is founder of Mucommune, LLC and currently serves as its interim CEO. S.K.L is also founder of Inhalon Biopharma, Inc, and currently serves as its CSO, Board of Director, and Scientific Advisory Board. S.K.L has equity interests in both Mucommune and Inhalon Biopharma; S.K.L’s relationships with Mucommune and Inhalon are subject to certain restrictions under University policy. The terms of these arrangements are managed by UNC-CH in accordance with its conflict of interest policies. T.R.M has equity interests in Inhalon Biopharma. B.S, A.S, T.M.J, T.R.M and S.K.L are inventors on patents licensed by Mucommune and Inhalon Biopharma.
Footnotes
Bhawana Shrestha: bhawana{at}email.unc.edu, Alison Schaefer: amschaef{at}email.unc.edu, Jamal Saada: jsaada{at}utmb.edu, Zhu Yong: yozhu{at}utmb.edu, Timothy M. Jacobs: timjacobs2{at}gmail.com, Elizabeth C. Chavez: ecchavez{at}bu.edu, Stuart S. Omsted: stuart{at}alum.mit.edu, Kathleen Vincent: klvincen{at}utmb.edu, Thomas R. Moench: Thomas.Moench{at}mappbio.com, Samuel K. Lai: lai{at}unc.edu