An mRNA vaccine for plague

在这个项目中，我们的目标是开发一种mRNA疫苗来对抗鼠疫，这种致命的疾病导致了14世纪的黑死病。在1347年瘟疫传入欧洲之后的几年里，大约有一半的人口在随后的大流行中丧生。鼠疫并没有消失，上一次大流行直到1960年才结束，从那时起，规模较小的疫情一直在继续。鼠疫在世界许多地区呈上升趋势，最近在非洲、中国、俄罗斯和美国报告了疫情。一些专家认为，近年来病例的增加可能是由气候变化引起的，正如人们认为的那样，气候变化在14世纪引发了这场大流行。引起鼠疫的细菌也被认为是一种生物武器，开发疫苗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，以保护面临疫情风险的人群，并防范未来的流行病，特别是那些生活在资源最有限地点、往往是拥挤环境中的人群。第一批疫苗是在1890年使用杀死的细菌生产的，但由于效力不确定和反应性，没有被广泛采用。由于需要多剂量（对疫情不实际）、需要佐剂以及规模化生产可能存在困难，制造蛋白质疫苗的尝试受到了限制。我们对多种细菌（包括鼠疫）使用病毒载体疫苗的经验表明，用于制造牛津-阿斯利康covid - 19疫苗的这一系统可以产生有效的免疫反应。重要的是，在产生免疫反应的下游机制中，mRNA和病毒载体疫苗之间存在相似之处，这使我们有信心能够制造鼠疫mRNA疫苗。针对covid - 19和其他病毒的mRNA疫苗的经验表明，生产时间表较短，生产规模相对简单，这意味着我们希望加速开发一种保护生命的产品。

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.