mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against <i>Acinetobacter baumannii</i>

Background: <i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) 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) <i>...

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Main Authors: Cong Liu, Xingyun Wang, Yueling Zheng, Xingyue Gao, Jiahui Jin, Xing Cheng, Yunjiao He, Peng George Wang
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/7/764
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Summary:Background: <i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) 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) <i>A. baumannii</i> poses a pressing threat to public health. To date, no commercially available vaccine against <i>A. baumannii</i> 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 <i>A. baumannii</i> 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 <i>A. baumannii</i> 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 <i>A. baumannii</i>, 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.
ISSN:2076-393X