mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against .

Background: () has emerged as a critical human pathogen, causing high mortality rates among hospitalized patients and frequently triggering nosocomial outbreaks. The increasing prevalence of multidrug-resistant (MDR) poses a pressing threat to public health. To date, no commercially available vaccine against has been developed for clinical use. messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines have emerged as a promising vaccination strategy.

Methods: In this work, we developed two mRNA vaccines targeting SmpA-PLD and the fusion protein of outer membrane proteins OmpK and Omp22. The mRNA was encapsulated in LNP and administered to BALB/c mice. We evaluated humoral and cellular immune responses, bacterial burden, inflammation, and protective efficacy against infection in a sepsis model.

Results: These mRNA vaccines triggered robust humoral and cellular immune responses in BALB/c mice, reduced bacterial burden and inflammation in sepsis models, and provided significant protection against infection. Notably, the OmpK-Omp22 vaccine exhibited superior protective efficacy, reducing bacterial loads in various organs and improving survival rates in the sepsis model compared to the SmpA-PLD vaccine.

Conclusions: Our findings demonstrate mRNA-LNP vaccine technology as a versatile and promising platform for the development of innovative therapeutics against , with the potential to mitigate acute disease and promote bacterial decolonization. These findings pave the way for the development of urgently needed and effective antibacterial vaccines.