An mRNA vaccine for Plague: design to clinical efficacy testing

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The purpose of this project is to develop a mRNA vaccine against the Plague that is easy and suitable for distribution and use in lower- and middle-income countries (LMICs). Plague is a deadly disease caused by bacteria called _Yersinia pestis_(_Y. pestis_). Plague has caused millions of deaths throughout recorded history, most notoriously in the 1300s the 'Black Death' Pandemic that ravaged in western Eurasia killing up to 60% of the population., Nowadays endemic outbreaks are still experienced in many LMICs today. _Y. pestis_ is also recognised as a serious bioterrorism threat. Only if diagnosed early, plague can be effectively treated with antibiotics. However, antibiotic-resistant strains of _Y. pestis_ have emerged and human to-human transmission of such strains was recently reported in the 2017 Madagascar outbreak raising concerns about the future effectiveness of antibiotics against plague. Therefore, a plague vaccine could be very useful in preventing future endemic/epidemic outbreaks in LMICs.The Pfizer/BioNTech and Moderna COVID-19 LNP-mRNA vaccines demonstrated effective vaccines against contagious viruses, but mRNA is yet to be used in as antibacterial vaccine in humans. The first report of full protection against a highly lethal bacteria by a single dose of mRNA-LNP vaccine, has been recently published by NeoVac Co-founder Professor Peer and IIBR with the study demonstrating that one dose of a novel mRNA-LNP vaccine in mice provided full protection against plague.Current problem with existing mRNA-LNP vaccines is long-term storage and transportation at below-freezing temperatures. This makes their distribution and use in LMICs very challenging and expensive. To tackle this, NeoVac has developed a large library of proprietary LNPs which are designed to be stable at fridge temperatures (2-8 oC), that can be easily distribute and reduce the cost of vaccines for LMICs.In this project, NeoVac will employ Prof. Peer group's published mRNA encoding for _Y. pestis_ antigens, which have recently been demonstrated as effective in a preclinical plague model. The mRNA will be used to produce a thermostable mRNA-LNP vaccine that can be stored in the fridge. The project will start with the manufacturing of mRNA sequences followed by encapsulation in to the LNPs and efficacy studies both in vitro and in vivo. The vaccine will then be manufactured on a larger scale sufficient for first-in-human clinical trials. The large-scale batch will be further evaluated for stability, toxicity and immunogenicity required to support a clinical trial application.