Bridging the oral vaccine efficacy gap for childhood diarrhoeal disease

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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.