Tisakova Lenka Podpera, Schwebs Timo, Berdaguer Rocío, von Freyberg Marina, Foessleitner Philipp, Kieninger Ann-Katrin, Poljak Albina, Corsini Lorenzo, Farr Alex
BioNTech R&D (Austria) GmbH, Vienna, Austria.
Medical University of Vienna, Department of Obstetrics and Gynaecology, Division of Obstetrics and Feto-Maternal Medicine, Vienna, Austria.
NPJ Biofilms Microbiomes. 2025 Aug 12;11(1):161. doi: 10.1038/s41522-025-00764-0.
Current treatments for bacterial vaginosis (BV) often result in recurrent disease. Gardnerella, a key player in BV pathogenesis, forms biofilms on vaginal epithelial cells. Recombinant endolysins have shown to specifically kill Gardnerella, but not commensal lactobacilli, in vitro. This study evaluated the pharmacodynamics of BNT331-endolysin (BNT331-EL) on vaginal samples from 49 women with BV (Nugent score ≥7, Amsel criteria, and clue cells). Whole genome sequencing confirmed BV-associated community state types IV-B and III, with Gardnerella dominating in 53% of samples and present in 86%. Ex vivo treatment with BNT331-EL reduced viable Gardnerella by ≥94% at 20-50 µg/mL over 19 h. L. iners was reduced by an average of 92% across samples, while L. crispatus proliferated where present in substantial amounts. Endolysin treatment effectively disrupted Gardnerella biofilms and reduced viable bacterial load in a time- and concentration-dependent manner. These results informed the definition of the treatment dose for a first-in-human trial with BNT331-EL.
目前用于治疗细菌性阴道病（BV）的方法常常导致疾病复发。加德纳菌是BV发病机制中的关键因素，可在阴道上皮细胞上形成生物膜。重组溶菌酶已显示在体外能特异性杀死加德纳菌，但不会杀死共生乳杆菌。本研究评估了BNT331-溶菌酶（BNT331-EL）对49名BV女性（ Nugent评分≥7、符合阿姆塞尔标准且有线索细胞）阴道样本的药效学。全基因组测序证实为与BV相关的IV-B和III型群落状态，加德纳菌在53%的样本中占主导地位，86%的样本中有该菌。在19小时内，用20 - 50µg/mL的BNT331-EL进行离体处理可使存活的加德纳菌减少≥94%。惰性乳杆菌在所有样本中平均减少了92%，而卷曲乳杆菌在大量存在的地方则增殖。溶菌酶处理有效地破坏了加德纳菌生物膜，并以时间和浓度依赖的方式降低了活菌载量。这些结果为BNT331-EL首次人体试验的治疗剂量定义提供了依据。
