Development of a novel multi-epitope subunit mRNA vaccine candidate to combat Acinetobacter baumannii

Abstract Acinetobacter baumannii, an opportunistic bacterium prevalent in various environment, is a significant cause of nosocomial infections in ICUs. As the causative agent of pneumonia, septicemia, and meningitis, A. baumannii typically exhibits multidrug resistance and is associated with poor pr...

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Main Authors: Shiyang Ma, Fei Zhu, Peipei Zhang, Yizhong Xu, Ziyou Zhou, Hang Yang, Caixia Tan, Jie Chen, Pinhua Pan
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84823-0
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author Shiyang Ma
Fei Zhu
Peipei Zhang
Yizhong Xu
Ziyou Zhou
Hang Yang
Caixia Tan
Jie Chen
Pinhua Pan
author_facet Shiyang Ma
Fei Zhu
Peipei Zhang
Yizhong Xu
Ziyou Zhou
Hang Yang
Caixia Tan
Jie Chen
Pinhua Pan
author_sort Shiyang Ma
collection DOAJ
description Abstract Acinetobacter baumannii, an opportunistic bacterium prevalent in various environment, is a significant cause of nosocomial infections in ICUs. As the causative agent of pneumonia, septicemia, and meningitis, A. baumannii typically exhibits multidrug resistance and is associated with poor prognosis, thus led to a challenge for researchers in developing new treatment and prevention methods. This study involved the development of a novel multi-epitope mRNA vaccine for A. baumannii and validation of in silico approaches was conducted. We screened 11 immunodominant epitopes for cytotoxic T cells, 5 for helper T cells, and 10 for Linear B-cell based on promising candidate proteins omp33-36, ompA and ompW, the selection of these three proteins is based on reverse vaccinology screening and previous work by other researchers. All predicted epitopes demonstrated strong antigenicity, immunogenicity without posing any potential harm to humans. Additionally, high conservancy is required to cover different strains. All epitopes, as well as adjuvants, were constructed into a final vaccine, which was further assessed by calculating its physicochemical properties. Next, we docked the vaccine protein with immune receptors and analyzed the complexes with dynamic simulations to evaluate its affinity to receptors. At last, the constructed sequence is translated to an mRNA sequence. The results indicated the constructed vaccine is capability of eliciting robust humoral and cellular immune responses, making it a promising candidate for protection against the targeted pathogen.
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spelling doaj-art-ddc4d335fa9a4b19bbd2781885c11fa92025-01-12T12:17:39ZengNature PortfolioScientific Reports2045-23222025-01-0115111610.1038/s41598-024-84823-0Development of a novel multi-epitope subunit mRNA vaccine candidate to combat Acinetobacter baumanniiShiyang Ma0Fei Zhu1Peipei Zhang2Yizhong Xu3Ziyou Zhou4Hang Yang5Caixia Tan6Jie Chen7Pinhua Pan8Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South UniversityDepartment of Infection Control Center of Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South UniversityDepartment of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South UniversityAbstract Acinetobacter baumannii, an opportunistic bacterium prevalent in various environment, is a significant cause of nosocomial infections in ICUs. As the causative agent of pneumonia, septicemia, and meningitis, A. baumannii typically exhibits multidrug resistance and is associated with poor prognosis, thus led to a challenge for researchers in developing new treatment and prevention methods. This study involved the development of a novel multi-epitope mRNA vaccine for A. baumannii and validation of in silico approaches was conducted. We screened 11 immunodominant epitopes for cytotoxic T cells, 5 for helper T cells, and 10 for Linear B-cell based on promising candidate proteins omp33-36, ompA and ompW, the selection of these three proteins is based on reverse vaccinology screening and previous work by other researchers. All predicted epitopes demonstrated strong antigenicity, immunogenicity without posing any potential harm to humans. Additionally, high conservancy is required to cover different strains. All epitopes, as well as adjuvants, were constructed into a final vaccine, which was further assessed by calculating its physicochemical properties. Next, we docked the vaccine protein with immune receptors and analyzed the complexes with dynamic simulations to evaluate its affinity to receptors. At last, the constructed sequence is translated to an mRNA sequence. The results indicated the constructed vaccine is capability of eliciting robust humoral and cellular immune responses, making it a promising candidate for protection against the targeted pathogen.https://doi.org/10.1038/s41598-024-84823-0Acinetobacter baumanniiMultiepitope vaccineMolecular dockingMolecular dynamicsmRNA vaccine
spellingShingle Shiyang Ma
Fei Zhu
Peipei Zhang
Yizhong Xu
Ziyou Zhou
Hang Yang
Caixia Tan
Jie Chen
Pinhua Pan
Development of a novel multi-epitope subunit mRNA vaccine candidate to combat Acinetobacter baumannii
Scientific Reports
Acinetobacter baumannii
Multiepitope vaccine
Molecular docking
Molecular dynamics
mRNA vaccine
title Development of a novel multi-epitope subunit mRNA vaccine candidate to combat Acinetobacter baumannii
title_full Development of a novel multi-epitope subunit mRNA vaccine candidate to combat Acinetobacter baumannii
title_fullStr Development of a novel multi-epitope subunit mRNA vaccine candidate to combat Acinetobacter baumannii
title_full_unstemmed Development of a novel multi-epitope subunit mRNA vaccine candidate to combat Acinetobacter baumannii
title_short Development of a novel multi-epitope subunit mRNA vaccine candidate to combat Acinetobacter baumannii
title_sort development of a novel multi epitope subunit mrna vaccine candidate to combat acinetobacter baumannii
topic Acinetobacter baumannii
Multiepitope vaccine
Molecular docking
Molecular dynamics
mRNA vaccine
url https://doi.org/10.1038/s41598-024-84823-0
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