Engineering highly multivalent sperm-binding IgG antibodies for potent non-hormonal female contraception

Shrestha, B.; Schaefer, A.; Saada, J.; Yong, Z.; Jacobs, T. M.; Chavez, E. C.; Omsted, S. S.; Vincent, K.; Moench, T. R.; Lai, S. K.

doi:10.1101/2020.04.22.055301

bioRxiv · 10.1101/2020.04.22.055301

Engineering highly multivalent sperm-binding IgG antibodies for potent non-hormonal female contraception

Shrestha, B.·Schaefer, A.·Saada, J.·Yong, Z.·Jacobs, T. M.·Chavez, E. C.·Omsted, S. S.·Vincent, K.·Moench, T. R.·Lai, S. K.

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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.

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Shrestha, B., Schaefer, A., Saada, J., Yong, Z., Jacobs, T. M., Chavez, E. C., Omsted, S. S., Vincent, K., Moench, T. R., Lai, S. K.. 2020-04-24. Engineering highly multivalent sperm-binding IgG antibodies for potent non-hormonal female contraception. https://doi.org/10.1101/2020.04.22.055301

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