Novel Bivalent mRNA-LNP Vaccine for Highly Effective Protection against Pneumonic Plague

Area of Science:

• Microbiology
• Immunology
• Vaccinology

Background:

• Yersinia pestis, the bacterium causing plague, poses a significant global health risk and biothreat.
• Existing medical interventions remain insufficient against this pathogen.

Purpose of the Study:

• To design and evaluate novel mRNA constructs encoding Y. pestis virulence factors LcrV and F1.
• To assess the immunogenicity and protective efficacy of these mRNA vaccines against pneumonic plague.

Main Methods:

• Development of two mRNA constructs for LcrV and assessment of a previously developed F1 mRNA construct.
• Evaluation of vaccine efficacy and immunogenicity in a mouse model of pneumonic plague.
• Testing against virulent wild-type and atypical Y. pestis strains.

Main Results:

• Combination mRNA vaccination with human Fc-conjugated F1 + LcrV induced significant immune activation.
• Substantial protection against intranasal Y. pestis challenge was observed.
• The vaccine was effective against diverse Y. pestis strains, including wild-type and unencapsulated variants.

Conclusions:

• This study provides the first comprehensive evaluation of mRNA vaccines for pneumonic plague prevention using novel LcrV and F1 constructs.
• The mRNA-lipid nanoparticle (LNP) platform shows promise for combating bacterial pathogens, including antibiotic-resistant strains.
• This innovative approach addresses critical gaps in current vaccination strategies for global health threats.