Bridging the oral vaccine efficacy gap for childhood diarrhoeal disease

缩小儿童腹泻病口服疫苗的功效差距

• 批准号: 10016052
• 金额: $ 60.99万
• 依托单位: CHAIN BIOTECHNOLOGY LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10016052
• 关键词: Bridging; oral; vaccine; efficacy; gap

CHAIN Biotechnology, a Nottingham-based biotech company and Dr Kelsey Jones, a Senior Research Fellow at University of Oxford plan to collaborate on a two-year project to develop a new type of vaccine to immunise against human rotavirus (HRV) infection. The vaccine should be highly effective for malnourished children susceptible to Childhood Diarrhoeal Disease (CDD).CDD is a global health problem affecting over 1.7 billion children every year and resulting in over 500,000 deaths, mainly in poorer countries. The most common cause of CDD is infection with human rotavirus (HRV). Vaccines that protect against HRV infection are available but relatively expensive, difficult to transport and administer in remote areas as they need to be kept cold. Also, they are ineffective in undernourished children. Consequently, it is much harder to prevent CDD in poorer countries.Existing HRV vaccines are based on oral ingestion of small doses of weakened virus and designed to trigger an immune response via immune tissue located in the small intestine. They interact with white blood cells present in the gut wall triggering the production of antibodies and memory cells that protect against future infection. However, these oral vaccines are not particularly effective in undernourished children.Dr Kelsey Jones has recently discovered that malnutrition destroys a branch of the immune system lining the small intestine required for vaccines to work. An unexpected finding was that the immune system in the large intestine (colon) remains largely unaffected.CHAIN has developed a way to deliver therapeutics including vaccines to the colon by genetic engineering a harmless microbe called Clostridium butyricum -- referred to as the CADD platform. CHAIN has engineered the bacterium to produce two key proteins from HRV. The bacteria are delivered orally, in a spore-form, and travel intact through the stomach and small intestine until they reach the colon where they germinate. The bacterial cells then grow and produce the HRV proteins necessary to trigger an immune response via the gut mucosa.The goal of this proposal is to test whether the CADD system can be used to bypass the immune defect present in under-nourished children. If successful, the results will be used to fast-track the development of a novel oral vaccine for HRV for clinical testing with the longer-term potential to transform the lives of millions of families across the world.

诺丁汉生物技术公司CHAIN Biotechnology和牛津大学高级研究员Kelsey Jones博士计划合作开展一项为期两年的项目，开发一种新型疫苗，对人类轮状病毒（HRV）感染进行免疫。这种疫苗对于易患儿童腹泻病的营养不良儿童应该非常有效。腹泻病是一个全球性的健康问题，每年影响17亿多儿童，造成50多万人死亡，主要发生在较贫穷的国家。CDD最常见的病因是人轮状病毒（HRV）感染。预防HRV感染的疫苗是可用的，但在偏远地区相对昂贵，难以运输和管理，因为它们需要冷藏。此外，它们对营养不良的儿童无效。因此，在较贫穷的国家预防CDD要困难得多。现有的HRV疫苗是基于口服小剂量的弱化病毒，旨在通过位于小肠的免疫组织触发免疫反应。它们与存在于肠壁的白细胞相互作用，触发抗体和记忆细胞的产生，以防止未来的感染。然而，这些口服疫苗对营养不良的儿童并不是特别有效。凯尔西·琼斯博士最近发现，营养不良会破坏小肠免疫系统的一个分支，而小肠免疫系统是疫苗发挥作用所必需的。一个意想不到的发现是，大肠（结肠）的免疫系统在很大程度上没有受到影响。CHAIN已经开发出一种方法，通过对一种名为丁酸梭菌的无害微生物进行基因工程改造，将包括疫苗在内的治疗药物输送到结肠，这种微生物被称为CADD平台。CHAIN对这种细菌进行了改造，使其从HRV中产生两种关键蛋白质。这种细菌以孢子的形式通过口腔传播，并完整地通过胃和小肠，直到到达结肠，在那里发芽。然后细菌细胞生长并产生HRV蛋白，通过肠道粘膜触发免疫反应。这项提议的目的是测试CADD系统是否可以用来绕过营养不良儿童的免疫缺陷。如果取得成功，研究结果将用于快速开发一种用于临床试验的新型HRV口服疫苗，这种疫苗具有改变全世界数百万家庭生活的长期潜力。