Next-generation mRNA vaccines eliciting robust protection against multidrug-resistant Enterobacteriaceae

This study reports the development of next-generation mRNA vaccines targeting multidrug-resistant Enterobacteriaceae by encoding a fusion of two novel antigens, PstS and YidR. The mRNA vaccines showed high in-vitro expression and secretion and provided strong protection in mouse models against Klebsiella pneumoniae and enterohemorrhagic Escherichia coli, with marked reductions in bacterial burden and organ damage. Notably, the K. pneumoniae-based vaccine (KV3) induced cross-protective immunity against multiple species, including K. pneumoniae, EHEC, Salmonella enterica, and Shigella flexneri. Overall, the findings highlight the promise of fusion-antigen mRNA vaccines as a strategy to combat multidrug-resistant Enterobacteriaceae with broad cross-protective potential.