Hexavalent sperm-binding IgG antibody released from vaginal film for development of potent on-demand nonhormonal female contraception

Bhawana Shrestha, Kathleen Vincent, Alison Schaefer, Yong Zhu, Gracie Vargas, Massoud Motamedi, Kelsi Swope, Josh Morton, Carrie Simpson, Henry Pham, Miles B. Brennan, Michael H. Pauly, Larry Zeitlin, Barry Bratcher, Kevin J. Whaley, Thomas R. Moench, Samuel K. Lai

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere2107832118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number48
DOIs
StatePublished - Nov 30 2021

Keywords

  • Antibody engineering
  • Contraception
  • Multivalent antibody
  • Vaginal film

ASJC Scopus subject areas

  • General

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