An mRNA vaccine for plague

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.