Biology subjects

Moench, T. R.

Publications and source records attributed to Moench, T. R..

3 recordsLinked to original sources

bioRxiv2021

Hexavalent Sperm-Binding IgG Antibody Released from Self-Dissolving Vaginal Film Enables Potent, On-Demand Non-Hormonal Female Contraception

Non-hormonal products for on-demand contraception are a global health technology gap, motivating us to pursue the use of sperm-binding monoclonal antibodies as a strategy to enable safe, effective, desirable, on-demand contraception. Here, using cGMP-compliant Nicotiana-expression system, we produce an ultra-potent 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) to reflect its molecular orientation. The Nicotiana-produced FIF exhibits 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 formulate the Nicotiana-produced FIF into a polyvinyl alcohol-based water-soluble contraceptive film, and evaluate its potency in reducing progressively motile sperm in the sheep vagina. Two minutes after vaginal instillation of human semen, no progressively motile sperm are recovered from the vaginas of sheep receiving FIF-Film. In contrast, high numbers of progressively motile sperm are recovered from sheep receiving a placebo film control. Our work supports the potential of highly multivalent contraceptive antibodies to provide safe, effective, on-demand non-hormonal contraception.

bioengineering↗

bioRxiv2020

Engineering Highly Homogenous Tetravalent IgGs with Enhanced Sperm Agglutination Potency

Millions of women avoid using available contraceptives and risk unintended pregnancies every year, due to perceived and/or real side-effects associated with the use of exogenous hormones. Naturally occurring anti-sperm antibodies can prevent fertilization in immune infertile women by limiting sperm permeation through mucus, particularly multivalent antibodies such as sIgA that offers robust agglutination potencies. Unfortunately, sIgA remains challenging to produce in large quantities and easily aggregates. Here, we designed two tetravalent anti-sperm IgGs with a Fab domain previously isolated from an immune infertile woman. Both constructs possess at least 4-fold greater agglutination potency and induced much more rapid sperm agglutination than the parent IgG while exhibiting comparable production yields and identical thermostability as the parent IgG. These tetravalent IgGs offer promise for non-hormonal contraception and underscore the multimerization of IgG as a promising strategy to improve existing mAb therapeutics.

molecular biology↗

bioRxiv2020

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

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.

molecular biology↗