A versatile capsule-intravaginal ring platform enables rapid and sustained release of monoclonal antibodies for...

Non-hormonal contraceptives that do not require use immediately before or after intercourse would likely meet the reproductive health needs of millions of women. We previously reported the engineering of MM008, a highly multivalent monoclonal antibody with 10 Fabs against a unique human sperm antigen, which agglutinates and prevents sperm from swimming through cervicovaginal mucus to reach eggs. Here, we report the development of a versatile capsule-intravaginal ring (IVR) platform that affords precise tuning of mAb release kinetics, enabling both rapid-on and sustained release of MM008 over 30 days into vaginal fluid simulants in vitro, while fully preserving activity and stability. In vivo, MM008-released from the capsule-IVR agglutinated all human sperm introduced into the sheep vagina within 1 min over a span of at least 21 days, a duration that covers the fertility window for women with menstrual cycles up to ∼39 days. MM008-IVR was safe and well tolerated in sheep. These results support further development of MM008-IVR as a long-acting non-hormonal contraceptive, and highlight the broader potential for the capsule-IVR platform to deliver diverse biologics to reinforce female reproductive health.