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

口服鼠疫疫苗的快速、简单生产和临床评价

• 批准号: 972211
• 金额: $ 131.95万
• 依托单位: PROKARIUM LIMITED
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=972211
• 关键词: Rapid; simple; manufacture; clinical; evaluation

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.

正如最近的疾病爆发所表明的那样，世界需要更快更好地开发、制造、测试和分发疫苗。Prokarium是一家总部位于英国的专注于口服疫苗的疫苗开发公司，与大多数注射疫苗相比，该公司从实验室到临床的时间可以缩短6-12个月，使用相同的制造工艺生产多种疫苗，可将成本降低高达70%，并在非常简单的门诊条件下对其口服疫苗进行临床测试。Prokarium的分娩菌株在471名志愿者（包括101名儿童）的10项1期和2期临床试验中建立了强有力的安全记录。在这个项目中，Prokarium将对其下一代疫苗平台“Vaxonella”进行临床试验，该平台商业化后可以在高达40摄氏度的温度下分发至少12周，并且在紧急情况下可以在不需要医务人员的情况下自行给药。这些是对抗严重疾病和潜在流行病（如鼠疫耶尔森氏菌引起的鼠疫）所需的疫苗特性。从历史上看，鼠疫导致了几次流行病，包括黑死病，在中世纪晚期，黑死病导致欧洲5000多万人死亡。如今，鼠疫仍在致人死亡，近年来，鼠疫流行的国家数量有所增加，导致世界卫生组织（World Health Organization）将其列为重新出现的疾病。再加上未来出现耐抗生素鼠疫杆菌菌株的风险，以及它有可能成为一种气溶胶递送的生物恐怖主义武器，因此有必要开发一种有效的疫苗。必须设计一种理想的鼠疫疫苗，以便在低收入和中等收入国家对高危人群（如马达加斯加、刚果民主共和国等）进行季节性免疫接种，并在水库人群受到干扰时迅速分发，以应对由洪水或地震等重大干扰引起的疫情。Prokarium的Vaxonella平台是基于活的沙门氏菌菌株，这些菌株被削弱了，因此它们不会引起疾病。沙门氏菌以胶囊或液体的形式口服给儿童服用，它们通过胃进入小肠，然后通过肠道内壁进入免疫系统的抗原呈递细胞。在这个项目中使用的沙门氏菌已经被编程，从人体自身的免疫细胞中表达两种来自鼠疫杆菌的蛋白抗原。这种有针对性的疫苗接种意味着所有免疫环节都被触发，包括第一道防线，即粘膜免疫。此外，由于消除了注射所需的昂贵纯化，制造成本降低了70%。Prokarium已经成功地在老鼠身上测试了一种鼠疫疫苗。现在，该公司将确认一种改进后的疫苗可以保护老鼠免受鼠疫菌的侵害，然后迅速制造一种液体悬浮液，然后在人类志愿者身上进行临床试验，在那里将测量安全性和免疫反应。这将为支持鼠疫疫苗的进一步开发提供信息，而且至关重要的是，这将首次证明下一代Vaxonella平台的概念，该平台可能改变疫苗的开发、生产和分发方式。