Bridging the oral vaccine efficacy gap for childhood diarrhoeal disease

总部位于诺丁汉的生物技术公司Chain Biotech和牛津大学高级研究员凯尔西·琼斯博士计划合作一个为期两年的项目，开发一种新型疫苗，以免疫人类轮状病毒(HRV)感染。该疫苗对易患儿童腹泻病(CDD)的营养不良儿童应该非常有效。CDD是一个全球健康问题，每年影响超过17亿儿童，导致超过50万人死亡，主要发生在较贫穷的国家。CDD最常见的原因是感染人类轮状病毒(HRV)。预防HRV感染的疫苗是可用的，但相对昂贵，很难在偏远地区运输和管理，因为它们需要保持低温。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的难度要大得多。现有的HRV疫苗是基于口服小剂量的减弱病毒，旨在通过位于小肠的免疫组织触发免疫反应。它们与肠壁中的白细胞相互作用，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，营养不良会破坏疫苗发挥作用所需的小肠免疫系统的一个分支。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已经开发出一种通过基因工程将疫苗等治疗药物输送到结肠的方法。这种无害的微生物被称为酪酸梭菌，被称为CADD平台。Chain已经对细菌进行了改造，使其从HRV中产生两种关键蛋白质。细菌以孢子的形式经口腔传播，并通过胃和小肠完好无损地传播，直到到达结肠，在那里发芽。然后细菌细胞生长并产生必要的HRV蛋白，通过肠道粘膜触发免疫反应。这项提议的目标是测试CADD系统是否可以用来绕过营养不良儿童存在的免疫缺陷。如果成功，这些结果将被用于快速开发一种用于临床测试的新型HRV口服疫苗，这种疫苗具有改变世界各地数百万家庭生活的长期潜力。

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.