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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author Cong Liu
Xingyun Wang
Yueling Zheng
Xingyue Gao
Jiahui Jin
Xing Cheng
Yunjiao He
Peng George Wang
author_facet Cong Liu
Xingyun Wang
Yueling Zheng
Xingyue Gao
Jiahui Jin
Xing Cheng
Yunjiao He
Peng George Wang
author_sort Cong Liu
collection DOAJ
description 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.
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spelling doaj-art-bb435b6068964d379bbdddd3cefe34ca2025-08-20T03:56:49ZengMDPI AGVaccines2076-393X2025-07-0113776410.3390/vaccines13070764mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against <i>Acinetobacter baumannii</i>Cong Liu0Xingyun Wang1Yueling Zheng2Xingyue Gao3Jiahui Jin4Xing Cheng5Yunjiao He6Peng George Wang7Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, ChinaDepartment of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen 518000, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, ChinaBackground: <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.https://www.mdpi.com/2076-393X/13/7/764mRNA vaccine<i>Acinetobacter baumannii</i>LNPbacterial infection
spellingShingle Cong Liu
Xingyun Wang
Yueling Zheng
Xingyue Gao
Jiahui Jin
Xing Cheng
Yunjiao He
Peng George Wang
mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against <i>Acinetobacter baumannii</i>
Vaccines
mRNA vaccine
<i>Acinetobacter baumannii</i>
LNP
bacterial infection
title mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against <i>Acinetobacter baumannii</i>
title_full mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against <i>Acinetobacter baumannii</i>
title_fullStr mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against <i>Acinetobacter baumannii</i>
title_full_unstemmed mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against <i>Acinetobacter baumannii</i>
title_short mRNA-LNP Vaccines Targeting SmpA-PLD and OmpK-Omp22 Induce Protective Immunity Against <i>Acinetobacter baumannii</i>
title_sort mrna lnp vaccines targeting smpa pld and ompk omp22 induce protective immunity against i acinetobacter baumannii i
topic mRNA vaccine
<i>Acinetobacter baumannii</i>
LNP
bacterial infection
url https://www.mdpi.com/2076-393X/13/7/764
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