Rapid, simple manufacture and clinical evaluation of an oral plague vaccine

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As recent disease outbreaks show, the world needs to be faster and better at developing, manufacturing, testing and distributing vaccines. Prokarium, a UK-based vaccine development company focusing on oral vaccines, can move from bench to clinic 6-12 months faster compared to most injectable vaccines, use the same manufacturing process to produce a wide range of vaccines, cut costs by up to 70% and clinically test its oral vaccines under very simple out-patient conditions. Prokarium’s delivery strain has established a strong safety record in 10 phase 1 and 2 clinical trials in 471 volunteers including 101 children. In this project Prokarium will clinically trial its next generation vaccine platform ‘Vaxonella’, which when commercialised can be distributed at temperatures of up to 40 C for at least 12 weeks and which in emergencies can be self-administered without the need for medical personnel. These are the vaccine characteristics needed to combat serious diseases and potential epidemics such as plague caused by the bacterium Yersinia pestis. Historically plague was responsible for several epidemics, including the Black Death, which killed over 50 million people in Europe in the late medieval period. Today plague still kills people and in recent years the number of countries where plague is endemic increased, resulting in the World Health Organization labelling it a re-emerging disease. Coupled with the risk of future antibiotic resistant strains of Y. pestis arising, and its potential as an aerosol-delivered bioterrorism weapon, there is a need to develop an effective vaccine. An ideal plague vaccine must be designed for use in low- and medium-income countries to immunise high risk populations (e.g. Madagascar, DRC, etc.) on a seasonal basis and to rapidly distribute in response to an outbreak caused by major disturbances such as floods or earthquakes when the reservoir populations are disturbed. Prokarium’s Vaxonella platform is based on live strains of Salmonella bacteria which are weakened so that they cannot cause disease. The Salmonella are taken orally as a capsule or liquid resuspension for children, they transit the stomach into the small intestine where they actively enter through the gut lining into the antigen-presenting cells of the immune system. The Salmonella to be used in this project have been programmed to express two protein antigens from Y. pestis from within the body’s own immune cells. This targeted vaccination means all arms of immunity are triggered including the first line of defence, namely mucosal immunity. Also, manufacturing is up to 70% cheaper because costly purification needed for injectables is eliminated. Prokarium has already successfully tested a plague vaccine in mice. Now it will confirm that an improved vaccine can protect mice against Y. pestis, then rapidly manufacture a liquid suspension, and then test it on human volunteers in a clinical trial, where the safety and immune response will be measured. This will provide information to support further development of the plague vaccine and crucially be the first proof of concept of the next generation Vaxonella platform that could transform the way vaccines are developed, manufactured and distributed.