Development of clinically translatable therapies for the treatment and prevention of bacterial vaginosis

本研究旨在开发治疗复发性细菌性阴道病（BV）的新疗法。细菌性阴道炎是育龄妇女最常见的阴道感染，多达30%的育龄妇女患有此病。细菌性阴道炎是由阴道内有害细菌的过度生长引起的。引起细菌性阴道炎的主要问题细菌是阴道加德纳菌。这种细菌通过性接触、胃肠道或阴道冲洗等其他活动传播，在阴道内繁殖，破坏正常生活在阴道环境中的健康、自然的细菌。文献研究表明，阴道芽孢杆菌作为一种被称为生物膜的粘性细菌结构的一部分生长：它为这种生物膜提供了初始结构，这种生物膜吸引了其他阴道病原体。虽然只有少数感染阴道支原体的妇女（携带者的六分之一）表现出细菌性阴道炎的心理痛苦症状（腥臭/灰白色分泌物），但所有携带者都面临性传播感染、流产（增加十倍）和早产（风险增加一倍）的风险增加。细菌性阴道炎最常见的治疗方法是开抗生素。然而，抗生素虽然能暂时缓解症状，但并不能防止细菌性阴道炎的复发。接受抗生素治疗的所有BV患者中有70%在9个月内复发。许多妇女在使用抗生素治疗细菌性阴道炎后出现鹅口疮，并且有许多关于耐抗生素阴道加德纳菌的报道。这些问题表明，传统抗生素对细菌性阴道炎的管理很差，可能是因为它们不能完全破坏阴道杆菌的生物膜。在这个项目中，我们将开发选择性靶向和破坏阴道加德纳菌的治疗方法，不像现有的抗生素那样没有针对性，并且非选择性地杀死健康的细菌。我们的疗法将通过摧毁生长在生物膜中的阴道加德纳菌，有效地治疗这种疾病。这与目前的抗生素相反，目前抗生素不能穿透和破坏这些生物膜，导致治疗完成后再生，导致复发。加德纳菌对我们的新疗法产生耐药性的可能性很低，这将允许它们作为产前保健辅助工具进行预防性使用，这对于目前的疗法来说是不可能的。这将减少与这种情况相关的流产/早产率。在这个项目中详细的研究将主要由CC生物技术有限公司与合作学术机构联合进行，并得到英国主要承包商组织的协助。在项目结束时，我们将开发候选疗法，准备进行动物安全性/有效性研究/人体临床试验。

This research aims to develop new therapies for the treatment of recurrent bacterial vaginosis (BV). BV is the most common vaginal infection experienced by women of childbearing age, with up to 30% of woman of this group affected by the condition. BV is caused by the overgrowth of unwanted bacteria within the vagina. The main problematic bacterium which causes BV is called Gardnerella vaginalis. Introduced from sexual contact, the GI tract or through other activities such as vaginal douching, this bacterium colonises the vagina, destroying the healthy, natural bacteria which normally live in the vaginal environment. Literature studies have shown that G. vaginalis grows as part of a sticky bacterial structure known as a biofilm: it provides the initial structure for this biofilm which attracts other vaginal pathogens.While only a minority of women infected with G. vaginalis (1/6th of carriers) display psychologically distressing symptoms of BV (foul-fishy odour/grey white discharge), all carriers of the condition face increased risks of STI transmission, miscarriage (ten-fold increase) and preterm birth (doubled risk).The most common treatment for BV is the prescription of antibiotics. However, while relieving symptoms temporarily, antibiotics don't prevent BV recurrence. 70% of all BV patients treated with antibiotics experience recurrence of BV within 9 months. Many women experience thrush following usage of antibiotics for BV, and there are a number of reports of antibiotic resistant Gardnerella vaginalis. These issues illustrate that BV is poorly managed by traditional antibiotics, likely because they fail to fully destroy the G. vaginalis biofilm.In this project, we will develop therapies which selectively target and destroy Gardnerella vaginalis, unlike existing antibiotics which are not targeted, and kill healthy bacteria non-selectively. Our therapeutics will effectively treat the condition, by destroying Gardnerella vaginalis growing in biofilm. This is in contrast to current antibiotics, which cannot currently penetrate and destroy these biofilms, resulting in regrowth after completion of therapy, leading to recurrence.The low likelihood of Gardnerella developing resistance to our new therapies will allow their preventative usage as a prenatal health aid, which is not possible for current therapies. This will reduce the rate of miscarriages/premature births associated with the condition.The research detailed in this project will primarily be conducted by CC Biotech Ltd, in association with collaborator academic institutions, with assistance from leading UK contractor organisations.At project conclusion, we will have developed candidate therapies which are ready for animal safety/efficacy studies/human clinical trials.