An mRNA vaccine for plague

在这个项目中，我们的目标是开发一种针对鼠疫的mRNA疫苗，鼠疫是一种致命的疾病，导致了14世纪的黑死病。在1347年鼠疫到达欧洲之后的几年里，大约一半的人口在随后的大流行中被消灭。鼠疫并没有消失，上一次大流行直到1960年才结束，从那时起，规模较小的疫情仍在继续。鼠疫在世界许多地区一直在增加，最近在非洲、中国、俄罗斯和美国报告了疫情。一些专家认为，近年来病例的上升可能是由气候变化推动的，就像人们认为14世纪的大流行是由气候变化引发的一样。引起鼠疫的细菌也被认为是一种生物武器，疫苗的开发被认为是生物防御的优先事项。仍然迫切需要一种安全有效的疫苗来保护有暴发风险的人口，并预防未来的流行病，特别是那些生活在资源最有限的地点、往往在拥挤的环境中的人。第一批疫苗是在1890年生产的，使用的是灭活细菌，但由于效力和反应性的不确定，疫苗没有被广泛采用。制造蛋白质疫苗的尝试受到多剂量(不适用于暴发)的需要、对佐剂的要求以及规模化生产的困难。我们使用针对各种细菌(包括鼠疫)的病毒载体疫苗的经验表明，用于制造牛津-阿斯利康COVID19疫苗的这个系统可以产生强大的免疫反应。重要的是，信使核糖核酸疫苗和病毒载体疫苗在产生免疫反应的下游机制上有相似之处，这使我们有信心能够制造出鼠疫信使核糖核酸疫苗。针对COVID19和其他病毒的mRNA疫苗的经验表明，制造时间较短，生产规模相对直接，这意味着我们预计将加快产品的开发，以保护生命。

In this project we aim to develop an mRNA vaccine against plague, the deadly disease which caused the Black Death in the 14th Century. Over the years following the arrival of plague in Europe in 1347 about half of the population was wiped out in the ensuing pandemic. Plague has not gone away, and the last pandemic only ended in 1960 and smaller outbreaks have continued since then. Plague has been on the increase in many parts of the world with outbreaks reported recently in Africa, China, Russia and the US. Some experts believe that the rise in cases in recent years may be driven by climate change, just as is thought to have initiated the pandemic in the 14th century. The bacteria that cause plague are also considered a biological weapon and development of a vaccine is considered a priority for biodefence.There remains an urgent need for a safe and effective vaccine to protect populations at risk of outbreaks and defend against future epidemics, particularly those living in the most resource limited locations often in crowded settings. The first vaccines were produced in 1890 using killed bacteria but have not been widely adopted as a result of uncertain efficacy and reactogenicity. Attempts to make protein vaccines have been limited by the need for multiple doses (not practical for outbreaks), requirement for adjuvants and there can be difficulties in scaling manufacturing.Our experience with the use of viral vector vaccines for a variety of bacteria (including plague) shows that this system that was used to make the Oxford-AstraZeneca COVID19 vaccine can result in production of potent immune response. Importantly there are similarities between mRNA and viral vector vaccines in the downstream mechanisms for making immune responses giving confidence that we will be able to make a plague mRNA vaccine. Experience with mRNA vaccines for COVID19 and other viruses has shown short manufacturing timelines and relatively straightforward upscaling of production, which means that we expect to accelerate development to a product to defend lives.