Production and characterization of a human antisperm monoclonal antibody against CD52g for topical contraception in women

Background: Approximately 40% of human pregnancies are unintended, indicating a need for more accept-able effective contraception methods. New antibody production systems make it possible to manufacture reagent-grade human monoclonal antibodies (mAbs) for clinical use. We used the Nicotiana platform to pro-duce a human antisperm mAb and tested its efficacy for on-demand topical contraception. Methods: Heavy and light chain variable region DNA sequences of a human IgM antisperm antibody derived from an infertile woman were inserted with human IgG(1) constant region sequences into an agrobacterium and transfected into Nicotiana benthamiana. The product, an IgG(1) mAb [Human Contraception Antibody (HCA)], was purified on Protein A columns, and QC was performed using the LabChip GXII Touch protein characterization system and SEC-HPLC. HCA was tested for antigen specificity by immunofluorescence and western blot assays, antisperm activity by sperm agglutination and complement dependent sperm immobili-zation assays, and safety in a human vaginal tissue (EpiVaginal (TM)) model. Findings: HCA was obtained at concentrations ranging from 0.4 to 4 mg/ml and consisted of > 90% IgG monomers. The mAb specifically reacted with a glycan epitope on CD52g, a glycoprotein produced in the male reproductive tract and found in abundance on sperm. HCA potently agglutinated sperm under a variety of relevant physiological conditions at concentrations >= 6.25 mu g/ml, and mediated complement-dependent sperm immobilization at con-centrations >= 1 mu g/ml. HCA and its immune complexes did not induce inflammation in EpiVaginalTM tissue. Interpretation: HCA, an IgG1 mAb with potent sperm agglutination and immobilization activity and a good safety profile, is a promising candidate for female contraception. (C) 2021 The Author(s). Published by Elsevier B.V.

Automated summary

The HCA mAb produced using the Nicotiana platform has potent sperm agglutination and immobilization activity at high concentrations, with a good safety profile, making it a promising candidate for female contraception.