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。BV是育龄妇女经历的最常见的阴道感染，该组中多达30%的妇女受到这种疾病的影响。BV是由阴道内有害细菌的过度生长引起的。引起BV的主要问题细菌被称为阴道加德纳菌。通过性接触、胃肠道或其他活动（如阴道冲洗）引入，这种细菌在阴道中定植，破坏正常生活在阴道环境中的健康天然细菌。文献研究表明，G.阴道分泌物作为一种粘性细菌结构的一部分生长，这种结构被称为生物膜：它为这种生物膜提供了最初的结构，从而吸引其他阴道病原体。迷走神经病（1/6的携带者）表现出BV的心理上令人痛苦的症状（恶臭-鱼腥味/灰色白色分泌物），所有这种状况的携带者面临增加的STI传播、流产（增加10倍）和早产（加倍风险）的风险。然而，虽然暂时缓解症状，抗生素不能防止BV复发。所有接受抗生素治疗的BV患者中，70%在9个月内复发。许多妇女在使用抗生素治疗BV后会出现鹅口疮，并且有许多关于抗生素耐药性加德纳菌的报道。这些问题表明，传统抗生素对细菌性阴道病的控制很差，可能是因为它们未能完全破坏G。在该项目中，我们将开发选择性靶向和破坏迷走加德纳菌的疗法，而不像现有的抗生素那样没有靶向，并且非选择性地杀死健康细菌。我们的疗法将有效地治疗这种情况，通过破坏生物膜中生长的加德纳菌。这与目前的抗生素相反，目前的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健康援助的预防性使用，这是目前的疗法所不可能的。这将减少与该疾病相关的流产/早产率。该项目中详细介绍的研究将主要由CC Biotech Ltd与合作学术机构联合进行，并得到英国领先承包商组织的协助。在项目结束时，我们将开发出可用于动物安全性/有效性研究/人体临床试验的候选疗法。

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.