Kushiro Keiichiro, Hammers Scott, Zhu Yong, Flowers Haley B, Dawson Lauren, Panjwani Alysha, Schaefer Alison, Quan David, Gibb Katherine, McSweeney Morgan, Cone Richard, Moench Thomas, Vincent Kathleen L, Lai Samuel K
Mucommune, LLC, Morrisville, NC 27560, USA.
Mucommune, LLC, Morrisville, NC 27560, USA.
J Control Release. 2025 Jun 10;382:113662. doi: 10.1016/j.jconrel.2025.113662. Epub 2025 Mar 27.
There are limited options available for safe and effective non-hormonal contraceptives or methods that block sexually transmitted diseases such as herpes simplex virus (HSV). Direct vaginal delivery of monoclonal antibodies (mAb) represents a promising approach toward both goals, but clinical translation has been limited by the lack of convenient dosage forms that can quickly and stably deliver mAbs without mess. Here, we report the development of fast-dissolving antibody tablets (FDAT) that allow for the complete release of fully functional mAbs within seconds in vaginal fluid simulants, and within two minutes in fresh human cervicovaginal mucus ex vivo. As proof-of-concept, we developed two FDAT formulations: one for HSV8, a potent neutralizing mAb against both HSV Type 1 and 2, and a second for MM008, a unique 10-Fab anti-sperm mAb that induces sperm agglutination and inhibits progressive sperm motility with picomolar potency. In sheep studies, vaginally inserted HSV8-FDAT achieved uniform distribution in different parts of the vagina within minutes, while fully maintaining HSV8 neutralization activity. Similarly, MM008-FDAT completely eliminated all progressively motile sperm within 2 min of human semen instillation. Finally, the FDATs were stable for at least 3 months of storage at room temperature within desiccated water-impermeant foil pouches, and repeated daily application of FDATs for 7 days was safe and well tolerated in sheep. These results underscore the potentials of the FDAT platform for delivery of biologic interventions to reinforce female reproductive health.
对于安全有效的非激素避孕药或能阻断诸如单纯疱疹病毒（HSV）等性传播疾病的方法，可用的选择有限。直接经阴道递送单克隆抗体（mAb）是实现这两个目标的一种有前景的方法，但临床转化受到限制，因为缺乏能快速、稳定递送mAb且不造成麻烦的便捷剂型。在此，我们报告了速溶抗体片（FDAT）的开发，其能在模拟阴道液中数秒内、在新鲜人宫颈阴道黏液离体环境中两分钟内实现完全释放功能完整的mAb。作为概念验证，我们开发了两种FDAT制剂：一种针对HSV8，这是一种对1型和2型HSV均具有强效中和作用的mAb；另一种针对MM008，这是一种独特的10 - Fab抗精子mAb，能诱导精子凝集并以皮摩尔效力抑制精子的前向运动能力。在绵羊研究中，经阴道插入的HSV8 - FDAT在数分钟内实现了在阴道不同部位的均匀分布，同时完全保持了HSV8的中和活性。同样，MM008 - FDAT在滴入人精液后2分钟内完全消除了所有具有前向运动能力的精子。最后，FDAT在干燥的不透水铝箔袋中于室温下储存至少3个月仍保持稳定，并且在绵羊中每天重复应用FDAT 7天是安全的且耐受性良好。这些结果强调了FDAT平台在递送生物干预措施以加强女性生殖健康方面的潜力。
