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

Area of Science:

• Microbiology
• Vaccinology
• Biotechnology

Background:

• Antimicrobial resistance (AMR) is a growing global health threat, diminishing the effectiveness of antibiotics.
• There is an urgent need for novel vaccines to combat multidrug-resistant (MDR) bacterial pathogens.

Purpose of the Study:

• To develop next-generation mRNA vaccines encoding novel antigens for protection against MDR Gram-negative bacteria.
• To evaluate the efficacy and cross-protective potential of these mRNA vaccines in preclinical models.

Main Methods:

• Development of mRNA vaccines encoding fusion proteins of phosphate-specific transport protein (PstS) and DUF3748 domain-containing protein (YidR).
• In vitro assessment of protein expression and secretion.
• In vivo efficacy studies in mice challenged with Klebsiella pneumoniae and enterohemorrhagic Escherichia coli (EHEC).
• Evaluation of cross-protection against other Enterobacteriaceae species.

Main Results:

• The novel fusion proteins (PstS-YidR) were highly expressed and secreted in vitro.
• mRNA vaccines conferred significant protection in mice against K. pneumoniae and EHEC, reducing bacterial load and organ damage.
• A K. pneumoniae-based mRNA vaccine (KV3) demonstrated cross-protection against K. pneumoniae, EHEC, Salmonella enterica, and Shigella flexneri.

Conclusions:

• Next-generation mRNA vaccines utilizing novel antigens are effective against MDR Enterobacteriaceae.
• The PstS-YidR fusion protein is a promising target antigen for developing broad-spectrum vaccines.
• These mRNA vaccines hold potential for combating MDR bacterial infections with significant cross-protective capabilities.