An Effective mRNA-LNP Vaccine Against the Lethal Plague Bacterium

Abstract

Plague is a rapidly deteriorating contagious disease that has killed millions of people during the history of mankind and is caused by the gram-negative bacterium Yersinia pestis. Currently, the disease is treated effectively with antibiotics. However, in the case of an outbreak caused by a multiple-antibiotic-resistant strain, alternative countermeasures are required. Despite the many efforts to develop a safe vaccine against the disease, there is still no vaccine approved for use in western countries. mRNA Lipid Nanoparticle (mRNA-LNP) vaccines have been demonstrated during the Covid-19 pandemic to be a versatile, clinically relevant, and rapidly manufactured vaccine platform. However, harnessing this platform for bacterial pathogens remains a formidable challenge. Here, we describe the design of several mRNA-LNP vaccine versions against Y. pestis, based on the F1 capsular antigen. We demonstrate that mRNA-LNP vaccines encoding the F1 antigen with either no signal sequences or conjugated to human Fc, provide substantial cellular and humoral responses. Most importantly, these vaccine candidates fully protect animals against Y. pestis infection. The results of this study suggest that mRNA-LNPs can be effective as anti-bacterial vaccines, and further developed to combat other bacterial pathogens, which are urgently needed, given the looming threat of antibiotic resistance. One-Sentence SummaryA novel mRNA-LNP vaccine against Y. pestis, the etiological agent of plague and the first documented mRNA-LNP vaccine to protect against a lethal bacterial pathogen infection.