Treatment of Recurrent Bacterial Vaginosis Using Engineered Probiotic Bacteria

使用工程益生菌治疗复发性细菌性阴道病

• 批准号: 10035355
• 金额: $ 59.47万
• 依托单位: CC BIOTECH LTD.
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10035355
• 关键词: Treatment; Recurrent; Bacterial; Vaginosis; Using

**Public description**This project aims to develop new therapies for the prevention of recurrent bacterial vaginosis (BV). Around 30% of women suffer from BV, making it the most common vaginal infection of women of childbearing age. 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 activities such as vaginal douching, this bacterium colonises the vagina, destroying the healthy, natural bacteria which normally live in the vaginal environment.All carriers of the _G. vaginalis_ face increased risks of STI transmission, miscarriage (ten-fold increase) and preterm birth (doubled risk). Some BV patients also experience psychologically distressing symptoms (foul-fishy odour/grey white discharge) which can significantly affect mental/sexual health.The most common BV treatment is the prescription of antibiotics. However, while relieving symptoms temporarily, antibiotics don't prevent BV recurrence. Recurrence usually occurs after a known events which encourage re-growth of _G. vaginalis_: this can include interaction with a new sexual partner or menstruation. 50% of BV patients who have been treated with antibiotics experience BV recurrence within 6 months of therapy. Importantly, antibiotics cannot be used preventatively to treat BV, as this type of usage of antibiotics could lead to the spread of antimicrobial resistance.In this project, we aim to develop a groundbreaking therapy which would help women to prevent BV before it starts. This therapy will take the form of a probiotic bacterium, to be administered into the vagina by the patient around key trigger events for BV.To develop this therapeutic, we will select a bacteria which is commonly found in the healthy vagina (Lactobacillus). We will then engineer it, to enable it to "detect" when _G. vaginalis_ is present. We will further modify our therapeutic bacterium so that when it "detects" the presence of _G. vaginalis_, it produces and releases an antimicrobial into the vaginal environment which specifically targets and kills _G. vaginalis_, preventing BV developement. This bacterial probiotic would be the first actively preventative therapy available for women who suffer recurrent/chronic BV, and help fully resolve a distressing condition which is associated with significant negative pre-natal health outcomes.The research detailed in this project will primarily be conducted by CC Biotech Ltd, in collaboration with academic institutions.At project conclusion, we will have developed a therapeutic probiotic which is ready for animal safety/efficacy studies/human clinical trials.

**公众描述**本项目旨在开发预防细菌性阴道病(BV)复发的新疗法。大约30%的妇女患有BV，使其成为育龄妇女最常见的阴道感染。BV是由阴道内多余的细菌过度生长引起的。引起BV的主要问题细菌是阴道加德纳氏菌。这种细菌从性接触、胃肠道或通过阴道冲洗等活动进入阴道，定植于阴道，摧毁通常生活在阴道环境中的健康自然细菌。所有阴道革兰氏菌携带者都面临着STI传播、流产(增加10倍)和早产(增加一倍的风险)的风险增加。一些BV患者还会出现令人痛苦的心理症状(臭味/灰色白色分泌物)，这可能会严重影响精神/性健康。最常见的BV治疗是抗生素处方。然而，虽然抗生素暂时缓解了症状，但并不能防止BV的复发。复发通常发生在已知的鼓励阴道毛滴虫再次生长的事件之后：这可能包括与新性伴侣或月经的互动。在接受抗生素治疗的BV患者中，50%的患者在治疗后6个月内出现BV复发。重要的是，抗生素不能预防性地用于治疗BV，因为这种类型的抗生素使用可能会导致抗菌素耐药性的传播。在这个项目中，我们的目标是开发一种突破性的疗法，帮助妇女在BV开始之前预防BV。这种疗法将采取益生菌的形式，由患者围绕BV的关键触发事件进入阴道。为了开发这种疗法，我们将选择一种在健康阴道中常见的细菌(乳杆菌)。然后，我们将对其进行改造，使其能够“检测”是否存在阴道毛滴虫。我们将进一步修改我们的治疗细菌，以便当它“检测”到阴道革兰氏杆菌的存在时，它会产生一种抗菌剂，并将其释放到阴道环境中，该抗菌剂专门针对并杀死阴道革兰氏菌，从而防止BV的发展。这种细菌益生菌将是第一种可用于患有复发/慢性BV的妇女的积极预防疗法，并有助于完全解决与重大的产前健康负面结果相关的痛苦状况。本项目中详细的研究将主要由CC Biotech Ltd与学术机构合作进行。在项目结束时，我们将开发出一种治疗性益生菌，为动物安全性/有效性研究/人类临床试验做好准备。