Cross-Serotype Protection of a PstS-YidR Fusion mRNA Vaccine Against Systemic Infection and Endogenous Endophthalmitis Caused by Hypervirulent Klebsiella pneumoniae.

Background: Hypervirulent Klebsiella pneumoniae (K. pneumoniae) easily causes bacteremia and liver abscess, and invades the eye via blood circulation to trigger blinding endogenous endophthalmitis. Widespread multidrug resistance limits antibiotic treatment, while traditional capsular polysaccharide vaccines cannot provide cross-serotype protection. Methods: We established a mouse model of intraperitoneal infection-induced endogenous endophthalmitis. BALB/c mice received two intramuscular injections of LNP-encapsulated PstS-YidR fusion mRNA vaccine, followed by challenge with hypervirulent K1 or K2 strains. We monitored body weight, quantified multi-tissue bacterial loads, detected IL-1β, IL-6 and TNF-α, and performed slit-lamp observation and liver/ocular histopathology. Results: The vaccine relieved systemic symptoms and weight loss, suppressed bacterial dissemination across peritoneal, blood, liver, lung and eye tissues, and reduced excessive inflammatory factor release. It alleviated intraocular suppurative lesions, preserved ocular structure, and mitigated liver abscess and hepatocellular necrosis, with equal protective efficacy against K1 and K2 and favorable in vivo safety. Conclusions: The PstS-YidR fusion mRNA vaccine blocks systemic spread and intraocular invasion of hypervirulent K. pneumoniae and alleviates multi-organ inflammatory damage. It serves as a safe candidate vaccine for preventing K1/K2-type hypervirulent Klebsiella infections and endogenous endophthalmitis.