A multi-target mRNA Vaccine Provides Cross-Prophylactic and Therapeutic Protection Against Diverse Pasteurellaceae Infections

Pasteurellaceae pathogens, including P. multocida, pose significant threats to humans, livestock, and poultry, while the effectiveness of antibiotic treatment is gradually being compromised by the problem of antibiotic resistance.Here, we developed a conserved multi-target mRNA vaccine strategy to achieve broadspectrum prevention and therapy against Pasteurellaceae infections.Six highly conserved intracellular antigens, with truncated sequence similarities all exceeding 91%, were selected for the development of a novel mRNA platform against Pasteurellaceae.In mouse models, the vaccine conferred strong protection against P. multocida and showed cross-protection against four Pasteurellaceae pathogens, reducing lung bacterial burden by up to 10-fold compared with the challenge control.In a rabbit acute pneumonia model, the vaccine significantly improved survival by over 40% and reduced lung pathology following P. multocida infection.Notably, repeated administration of vaccine exhibited preliminary therapeutic efficacy in naturally infected animals, including one cat, piglets (with a 40% reduction in infection rate), and laying hens (with an approximately 20% increase in egg production), resulting in bacterial burden and alleviation of clinical symptoms.These findings demonstrate that a conserved multi-antigen mRNA vaccine can induce broad-spectrum protective effect against Pasteurellaceae pathogens.