{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:52:58Z","timestamp":1791499978821,"version":"4.3.4"},"reference-count":117,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Youth Science and Technology Top Talent Program","award":["2022TSYCCX0112"],"award-info":[{"award-number":["2022TSYCCX0112"]}]},{"name":"Xinjiang Uygur Autonomous Region Science and Technology Support Project","award":["2022E02061"],"award-info":[{"award-number":["2022E02061"]}]},{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia Fund","award":["SKL-HIDCA2021-JH11"],"award-info":[{"award-number":["SKL-HIDCA2021-JH11"]}]},{"name":"Science and Technology Department of Xinjiang Uygur Autonomous Region, Outstanding Youth Project","award":["2022D01E69"],"award-info":[{"award-number":["2022D01E69"]}]},{"name":"National Natural Science Foundation of China and regional science foundation projects","award":["32160182"],"award-info":[{"award-number":["32160182"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Brucellosis and Tuberculosis, both of which are contagious diseases, have presented significant challenges to global public health security in recent years. Delayed treatment can exacerbate the conditions, jeopardizing patient lives. Currently, no vaccine has been approved to prevent these two diseases simultaneously. In contrast to traditional vaccines, mRNA vaccines offer advantages such as high efficacy, rapid development, and low cost, and their applications are gradually expanding. This study aims to develop multi-epitope mRNA vaccines argeting Brucella melitensis and Mycobacterium tuberculosis H37Rv (L4 strain) utilizing immunoinformatics approaches. The proteins Omp25, Omp31, MPT70, and MPT83 from the specified bacteria were selected to identify the predominant T- and B-cell epitopes for immunological analysis. Following a comprehensive evaluation, a vaccine was developed using helper T lymphocyte epitopes, cytotoxic T lymphocyte epitopes, linear B-cell epitopes, and conformational B-cell epitopes. It has been demonstrated that multi-epitope mRNA vaccines exhibit increased antigenicity, non-allergenicity, solubility, and high stability. The findings from molecular docking and molecular dynamics simulation revealed a robust and enduring binding affinity between multi-epitope peptides mRNA vaccines and TLR4. Ultimately, Subsequently, following the optimization of the nucleotide sequence, the codon adaptation index was calculated to be 1.0, along with an average GC content of 54.01%. This indicates that the multi-epitope mRNA vaccines exhibit potential for efficient expression within the <jats:italic>Escherichia coli(E<\/jats:italic>. <jats:italic>coli)<\/jats:italic> host. Analysis through immune modeling indicates that following administration of the vaccine, there may be variation in immunecell populations associated with both innate and adaptive immune reactions. These types encompass helper T lymphocytes (HTL), cytotoxic T lymphocytes (CTL), regulatory T lymphocytes, natural killer cells, dendritic cells and various immune cell subsets. In summary, the results suggest that the newly created multi-epitope mRNA vaccine exhibits favorable attributes, offering novel insights and a conceptual foundation for potential progress in vaccine development.<\/jats:p>","DOI":"10.1371\/journal.pone.0309560","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T17:26:37Z","timestamp":1730136397000},"page":"e0309560","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Novel dual-pathogen multi-epitope mRNA vaccine development for Brucella melitensis and Mycobacterium tuberculosis in silico approach"],"prefix":"10.1371","volume":"19","author":[{"given":"Yuejie","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huidong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyu","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwei","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5795-8672","authenticated-orcid":true,"given":"Fengbo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"pone.0309560.ref001","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41392-018-0006-9","article-title":"miRNAs reshape immunity and inflammatory responses in bacterial infection","volume":"3","author":"X Zhou","year":"2018","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"pone.0309560.ref002","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13567-019-0650-2","article-title":"Acetate metabolic requirement of avian pathogenic Escherichia coli promotes its intracellular proliferation within macrophage","volume":"50","author":"X Zhuge","year":"2019","journal-title":"Vet Res"},{"issue":"1","key":"pone.0309560.ref003","doi-asserted-by":"crossref","first-page":"6368","DOI":"10.1038\/s41598-020-62472-3","article-title":"Genome-wide unique insertion sequences among five Brucella species and demonstration of differential identification of Brucella by multiplex PCR assay","volume":"10","author":"S Paul","year":"2020","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0309560.ref004","doi-asserted-by":"crossref","first-page":"e0206334","DOI":"10.1371\/journal.pone.0206334","article-title":"Insights into the genetic diversity of Mycobacterium tuberculosis in Tanzania","volume":"14","author":"LK Rutaihwa","year":"2019","journal-title":"PLoS One"},{"key":"pone.0309560.ref005","doi-asserted-by":"crossref","first-page":"1253349","DOI":"10.3389\/fmicb.2023.1253349","article-title":"Immuno-profiling of Brucella proteins for developing improved vaccines and DIVA capable serodiagnostic assays for brucellosis","volume":"14","author":"P Nandini","year":"2023","journal-title":"Front Microbiol"},{"key":"pone.0309560.ref006","article-title":"Update on the diagnosis of tuberculosis","author":"I Kontsevaya","year":"2023","journal-title":"Clin Microbiol Infect"},{"key":"pone.0309560.ref007","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.3389\/fmicb.2017.02039","article-title":"A Novel TetR-Like Transcriptional Regulator Is Induced in Acid-Nitrosative Stress and Controls Expression of an Efflux Pump in Mycobacteria","volume":"8","author":"F Perrone","year":"2017","journal-title":"Front Microbiol"},{"issue":"1","key":"pone.0309560.ref008","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1038\/s41598-020-80899-6","article-title":"In silico analysis of epitope-based vaccine candidate against tuberculosis using reverse vaccinology","volume":"11","author":"S Bibi","year":"2021","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0309560.ref009","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics10030105","article-title":"New Ways to Treat Tuberculosis Using Dendrimers as Nanocarriers","volume":"10","author":"S Mignani","year":"2018","journal-title":"Pharmaceutics"},{"key":"pone.0309560.ref010","article-title":"Novel Targets for the Development of Tuberculosis Vaccine","author":"R Joshi","year":"2024","journal-title":"Curr Drug Discov Technol"},{"issue":"1","key":"pone.0309560.ref011","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s43141-023-00614-6","article-title":"Immunoinformatics analysis of Brucella melitensis to approach a suitable vaccine against brucellosis","volume":"21","author":"P Hashemzadeh","year":"2023","journal-title":"J Genet Eng Biotechnol"},{"issue":"1","key":"pone.0309560.ref012","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12889-017-5016-y","article-title":"Brucellosis remains a neglected disease in the developing world: a call for interdisciplinary action","volume":"18","author":"KA Franc","year":"2018","journal-title":"BMC Public Health"},{"issue":"3","key":"pone.0309560.ref013","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1016\/S1473-3099(19)30625-5","article-title":"The status of tuberculosis vaccine development","volume":"20","author":"LK Schrager","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"pone.0309560.ref014","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.1017\/S0950268821001229","article-title":"Design of a new multi-epitope vaccine against Brucella based on T and B cell epitopes using bioinformatics methods","volume":"149","author":"Z Chen","year":"2021","journal-title":"Epidemiol Infect"},{"issue":"12","key":"pone.0309560.ref015","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1080\/21645515.2017.1329788","article-title":"An immunoinformatics-derived DNA vaccine encoding human class II T cell epitopes of Ebola virus, Sudan virus, and Venezuelan equine encephalitis virus is immunogenic in HLA transgenic mice","volume":"13","author":"CE Bounds","year":"2017","journal-title":"Hum Vaccin Immunother"},{"issue":"1","key":"pone.0309560.ref016","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41392-023-01579-1","article-title":"mRNA vaccines in disease prevention and treatment","volume":"8","author":"G Zhang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"pone.0309560.ref017","doi-asserted-by":"crossref","first-page":"2680160","DOI":"10.1155\/2017\/2680160","article-title":"Fundamentals and Methods for T- and B-Cell Epitope Prediction","volume":"2017","author":"JL Sanchez-Trincado","year":"2017","journal-title":"J Immunol Res"},{"issue":"5","key":"pone.0309560.ref018","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1002\/vms3.537","article-title":"Evaluation of the immunogenicity and efficacy of a chimeric OMP25-OMP31 antigen in BALB\/c mice","volume":"7","author":"Y. Mohammadi","year":"2021","journal-title":"Vet Med Sci"},{"issue":"1","key":"pone.0309560.ref019","doi-asserted-by":"crossref","first-page":"6658","DOI":"10.1038\/s41467-021-26934-0","article-title":"A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Gu\u00e9rin","volume":"12","author":"JS Woodworth","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0309560.ref020","doi-asserted-by":"crossref","first-page":"104318","DOI":"10.1016\/j.micpath.2020.104318","article-title":"Bioinformatics analysis of candidate proteins Omp2b, P39 and BLS for Brucella multivalent epitope vaccines","volume":"147","author":"T Sha","year":"2020","journal-title":"Microb Pathog"},{"issue":"11","key":"pone.0309560.ref021","article-title":"Alum Pickering Emulsion as Effective Adjuvant to Improve Malaria Vaccine Efficacy","volume":"9","author":"Q Chen","year":"2021","journal-title":"Vaccines (Basel)"},{"issue":"8","key":"pone.0309560.ref022","doi-asserted-by":"crossref","first-page":"100591","DOI":"10.1016\/j.mcpro.2023.100591","article-title":"UniProt and Mass Spectrometry-Based Proteomics-A 2-Way Working Relationship","volume":"22","author":"EH Bowler-Barnett","year":"2023","journal-title":"Mol Cell Proteomics"},{"issue":"3","key":"pone.0309560.ref023","article-title":"2 Hydroxybutyric Acid-Producing Bacteria in Gut Microbiome and Fusobacterium nucleatum Regulates 2 Hydroxybutyric Acid Level In Vivo","volume":"13","author":"F Qin","year":"2023","journal-title":"Metabolites"},{"issue":"4","key":"pone.0309560.ref024","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1002\/jmv.26596","article-title":"Vaccine design based on 16 epitopes of SARS-CoV-2 spike protein","volume":"93","author":"J He","year":"2021","journal-title":"J Med Virol"},{"issue":"2","key":"pone.0309560.ref025","doi-asserted-by":"crossref","first-page":"e0299169","DOI":"10.1371\/journal.pone.0299169","article-title":"Pro-SMP finder-A systematic approach for discovering small membrane proteins in prokaryotes","volume":"19","author":"T Hoffman","year":"2024","journal-title":"PLoS One"},{"issue":"2","key":"pone.0309560.ref026","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1080\/21645515.2019.1703453","article-title":"In silico identification and modification of T cell epitopes in pertussis antigens associated with tolerance","volume":"16","author":"C Kruiswijk","year":"2020","journal-title":"Hum Vaccin Immunother"},{"issue":"7","key":"pone.0309560.ref027","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41587-021-01156-3","article-title":"SignalP 6.0 predicts all five types of signal peptides using protein language models","volume":"40","author":"F Teufel","year":"2022","journal-title":"Nat Biotechnol"},{"key":"pone.0309560.ref028","doi-asserted-by":"crossref","first-page":"1067463","DOI":"10.3389\/fimmu.2022.1067463","article-title":"HLA variants have different preferences to present proteins with specific molecular functions which are complemented in frequent haplotypes","volume":"13","author":"V Karnaukhov","year":"2022","journal-title":"Front Immunol"},{"issue":"8","key":"pone.0309560.ref029","doi-asserted-by":"crossref","first-page":"e0286358","DOI":"10.1371\/journal.pone.0286358","article-title":"Design of multi-epitope vaccine candidate against Brucella type IV secretion system (T4SS)","volume":"18","author":"Z Yin","year":"2023","journal-title":"PLoS One"},{"issue":"W1","key":"pone.0309560.ref030","doi-asserted-by":"crossref","first-page":"W526","DOI":"10.1093\/nar\/gkae407","article-title":"Next-generation IEDB tools: a platform for epitope prediction and analysis","volume":"52","author":"Z Yan","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0309560.ref031","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12985-024-02337-7","article-title":"A computational approach to design a multiepitope vaccine against H5N1 virus","volume":"21","author":"F Dashti","year":"2024","journal-title":"Virol J"},{"key":"pone.0309560.ref032","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3389\/fimmu.2018.00678","article-title":"The CD8 T Cell Response to Respiratory Virus Infections","volume":"9","author":"ME Schmidt","year":"2018","journal-title":"Front Immunol"},{"issue":"12","key":"pone.0309560.ref033","article-title":"Immunoinformatics Analysis of SARS-CoV-2 ORF1ab Polyproteins to Identify Promiscuous and Highly Conserved T-Cell Epitopes to Formulate Vaccine for Indonesia and the World Population","volume":"9","author":"M Gustiananda","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"pone.0309560.ref034","doi-asserted-by":"crossref","first-page":"e11232","DOI":"10.7717\/peerj.11232","article-title":"Bioinformatic prediction of immunodominant regions in spike protein for early diagnosis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)","volume":"9","author":"S Zhuang","year":"2021","journal-title":"PeerJ"},{"issue":"1","key":"pone.0309560.ref035","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s12985-024-02424-9","article-title":"Genetic variability of human papillomavirus type 18 based on E6, E7 and L1 genes in central China","volume":"21","author":"T Li","year":"2024","journal-title":"Virol J"},{"key":"pone.0309560.ref036","doi-asserted-by":"crossref","first-page":"e9855","DOI":"10.7717\/peerj.9855","article-title":"Computational perspectives revealed prospective vaccine candidates from five structural proteins of novel SARS corona virus 2019 (SARS-CoV-2)","volume":"8","author":"R Anand","year":"2020","journal-title":"PeerJ"},{"issue":"28","key":"pone.0309560.ref037","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.1016\/j.vaccine.2018.05.106","article-title":"Multi-epitope DnaK peptide vaccine against S.Typhi: An in silico approach","volume":"36","author":"S Verma","year":"2018","journal-title":"Vaccine"},{"issue":"1","key":"pone.0309560.ref038","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s11756-021-00934-3","article-title":"Engineering a multi-epitope vaccine candidate against Leishmania infantum using comprehensive Immunoinformatics methods","volume":"77","author":"M Shams","year":"2022","journal-title":"Biologia (Bratisl)"},{"issue":"3","key":"pone.0309560.ref039","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1039\/D2FO03776A","article-title":"Identification of umami peptides based on virtual screening and molecular docking from Atlantic cod (Gadus morhua)","volume":"14","author":"Y Wang","year":"2023","journal-title":"Food Funct"},{"issue":"9","key":"pone.0309560.ref040","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1002\/jmv.27040","article-title":"Can molecular mimicry explain the cytokine storm of SARS-CoV-2?: An in silico approach","volume":"93","author":"G. Obando-Pereda","year":"2021","journal-title":"J Med Virol"},{"issue":"9","key":"pone.0309560.ref041","article-title":"Development of a Conserved Chimeric Vaccine for Induction of Strong Immune Response against Staphylococcus aureus Using Immunoinformatics Approaches","volume":"9","author":"R Chatterjee","year":"2021","journal-title":"Vaccines (Basel)"},{"issue":"5","key":"pone.0309560.ref042","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/s41596-020-0312-x","article-title":"The HDOCK server for integrated protein-protein docking","volume":"15","author":"Y Yan","year":"2020","journal-title":"Nat Protoc"},{"issue":"10","key":"pone.0309560.ref043","doi-asserted-by":"crossref","DOI":"10.3390\/cells10102646","article-title":"Molecular Basis of a Dominant SARS-CoV-2 Spike-Derived Epitope Presented by HLA-A*02:01 Recognised by a Public TCR","volume":"10","author":"C Szeto","year":"2021","journal-title":"Cells"},{"issue":"9","key":"pone.0309560.ref044","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph19095568","article-title":"Vaccinomics to Design a Multi-Epitopes Vaccine for Acinetobacter baumannii","volume":"19","author":"M Ud-Din","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0309560.ref045","doi-asserted-by":"crossref","first-page":"113216","DOI":"10.1016\/j.jim.2022.113216","article-title":"A vaccine built from potential immunogenic pieces derived from the SARS-CoV-2 spike glycoprotein: A computational approximation","volume":"502","author":"J. Marchan","year":"2022","journal-title":"J Immunol Methods"},{"issue":"4","key":"pone.0309560.ref046","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/eji.201646799","article-title":"Human \u03b2-defensin 3 increases the TLR9-dependent response to bacterial DNA","volume":"47","author":"SL McGlasson","year":"2017","journal-title":"Eur J Immunol"},{"issue":"1","key":"pone.0309560.ref047","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13568-018-0573-8","article-title":"Expression of recombinant HBD3 protein that reduces Mycobacterial infection capacity","volume":"8","author":"F Su","year":"2018","journal-title":"AMB Express"},{"key":"pone.0309560.ref048","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.3389\/fmicb.2020.02078","article-title":"Delineating the Immuno-Dominant Antigenic Vaccine Peptides Against gacS-Sensor Kinase in Acinetobacter baumannii: An in silico Investigational Approach","volume":"11","author":"AS Smiline Girija","year":"2020","journal-title":"Front Microbiol"},{"issue":"1","key":"pone.0309560.ref049","doi-asserted-by":"crossref","DOI":"10.3390\/molecules29010209","article-title":"Plant-Derived Proteins and Peptides as Potential Immunomodulators","volume":"29","author":"I Szerszunowicz","year":"2023","journal-title":"Molecules"},{"issue":"6","key":"pone.0309560.ref050","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/prot.25674","article-title":"NetSurfP-2.0: Improved prediction of protein structural features by integrated deep learning","volume":"87","author":"MS Klausen","year":"2019","journal-title":"Proteins"},{"issue":"7873","key":"pone.0309560.ref051","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"J Jumper","year":"2021","journal-title":"Nature"},{"issue":"1","key":"pone.0309560.ref052","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1038\/s41598-024-53048-6","article-title":"Immunoinformatics, molecular docking and dynamics simulation approaches unveil a multi epitope-based potent peptide vaccine candidate against avian leukosis virus","volume":"14","author":"SO Elshafei","year":"2024","journal-title":"Sci Rep"},{"issue":"10","key":"pone.0309560.ref053","article-title":"Vaccinomics-Aided Development of a Next-Generation Chimeric Vaccine against an Emerging Threat: Mycoplasma genitalium","volume":"10","author":"K Khalid","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"pone.0309560.ref054","doi-asserted-by":"crossref","first-page":"1091004","DOI":"10.3389\/fimmu.2022.1091004","article-title":"A multi-epitope vaccine GILE against Echinococcus Multilocularis infection in mice","volume":"13","author":"P Zhou","year":"2022","journal-title":"Front Immunol"},{"issue":"6","key":"pone.0309560.ref055","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21062243","article-title":"Accurate Representation of Protein-Ligand Structural Diversity in the Protein Data Bank (PDB)","volume":"21","author":"NK Shinada","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0309560.ref056","doi-asserted-by":"crossref","first-page":"7278","DOI":"10.1038\/s41598-024-57793-6","article-title":"In silico designed novel multi-epitope mRNA vaccines against Brucella by targeting extracellular protein BtuB and LptD","volume":"14","author":"J Shi","year":"2024","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0309560.ref057","doi-asserted-by":"crossref","first-page":"e0285177","DOI":"10.1371\/journal.pone.0285177","article-title":"In silico design and validation of a novel multi-epitope vaccine candidate against structural proteins of Chikungunya virus using comprehensive immunoinformatics analyses","volume":"18","author":"S Mahmoodi","year":"2023","journal-title":"PLoS One"},{"issue":"6","key":"pone.0309560.ref058","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23063050","article-title":"The Family Keeps on Growing: Four Novel Fungal OYEs Characterized","volume":"23","author":"MS Robescu","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"5","key":"pone.0309560.ref059","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41419-018-0463-7","article-title":"APR-246 reactivates mutant p53 by targeting cysteines 124 and 277","volume":"9","author":"Q Zhang","year":"2018","journal-title":"Cell Death Dis"},{"issue":"1","key":"pone.0309560.ref060","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1021\/acs.jctc.9b00591","article-title":"ff19SB: Amino-Acid-Specific Protein Backbone Parameters Trained against Quantum Mechanics Energy Surfaces in Solution","volume":"16","author":"C Tian","year":"2020","journal-title":"J Chem Theory Comput"},{"issue":"8","key":"pone.0309560.ref061","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27082483","article-title":"Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-\u03b2 Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation","volume":"27","author":"H Okumura","year":"2022","journal-title":"Molecules"},{"key":"pone.0309560.ref062","doi-asserted-by":"crossref","first-page":"40452","DOI":"10.1038\/srep40452","article-title":"Molecular dynamics studies unravel role of conserved residues responsible for movement of ions into active site of DHBPS","volume":"7","author":"RN Shinde","year":"2017","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0309560.ref063","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1080\/07391102.2020.1835732","article-title":"Caffeine and caffeine-containing pharmaceuticals as promising inhibitors for 3-chymotrypsin-like protease of SARS-CoV-2","volume":"40","author":"AO Elzupir","year":"2022","journal-title":"J Biomol Struct Dyn"},{"issue":"7","key":"pone.0309560.ref064","doi-asserted-by":"crossref","first-page":"e0307501","DOI":"10.1371\/journal.pone.0307501","article-title":"Identification of potent inhibitors of HDAC2 from herbal products for the treatment of colon cancer: Molecular docking, molecular dynamics simulation, MM\/GBSA calculations, DFT studies, and pharmacokinetic analysis","volume":"19","author":"M Khanal","year":"2024","journal-title":"PLoS One"},{"issue":"5","key":"pone.0309560.ref065","first-page":"e14085","article-title":"Identification of potential target endoribonuclease NSP15 inhibitors of SARS-COV-2 from natural products through high-throughput virtual screening and molecular dynamics simulation","volume":"46","author":"LC Hu","year":"2022","journal-title":"J Food Biochem"},{"key":"pone.0309560.ref066","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/07391102.2024.2349527","article-title":"Enhancing MD simulations: ASGARD\u2019s automated analysis for GROMACS","author":"A Rodr\u00edguez-Mart\u00ednez","year":"2024","journal-title":"J Biomol Struct Dyn"},{"key":"pone.0309560.ref067","doi-asserted-by":"crossref","first-page":"50","DOI":"10.3389\/fnmol.2019.00050","article-title":"Evolutionary-Conserved Allosteric Properties of Three Neuronal Calcium Sensor Proteins","volume":"12","author":"V Marino","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"pone.0309560.ref068","article-title":"In Silico Design of CT26 Polytope and its Surface Display by ClearColi\u2122-Derived Outer Membrane Vesicles as a Cancer Vaccine Candidate Against Colon Carcinoma","author":"E Sharif","year":"2024","journal-title":"Appl Biochem Biotechnol"},{"key":"pone.0309560.ref069","doi-asserted-by":"crossref","first-page":"105150","DOI":"10.1016\/j.micpath.2021.105150","article-title":"Prioritization of potential vaccine candidates and designing a multiepitope-based subunit vaccine against multidrug-resistant Salmonella Typhi str. CT18: A subtractive proteomics and immunoinformatics approach","volume":"159","author":"Y Chand","year":"2021","journal-title":"Microb Pathog"},{"issue":"6","key":"pone.0309560.ref070","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.gpb.2019.11.013","article-title":"Specificity of mRNA Folding and Its Association with Evolutionarily Adaptive mRNA Secondary Structures","volume":"19","author":"G Yu","year":"2021","journal-title":"Genomics Proteomics Bioinformatics"},{"issue":"7","key":"pone.0309560.ref071","doi-asserted-by":"crossref","DOI":"10.3390\/genes14071337","article-title":"Comparative Analysis of CRISPR-Cas Systems in Pseudomonas Genomes","volume":"14","author":"\u00c1 Parra-S\u00e1nchez","year":"2023","journal-title":"Genes (Basel)"},{"issue":"1","key":"pone.0309560.ref072","first-page":"54","article-title":"Molecular mimicry between Plasmodium sp and Guillain-Barre syndrome antigens","volume":"71","author":"YM Emiliani-Navarro","year":"2024","journal-title":"Rev Alerg Mex"},{"issue":"3","key":"pone.0309560.ref073","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.3758\/s13428-022-01835-2","article-title":"Precise display time measurement in JavaScript for web-based experiments","volume":"55","author":"G Luk\u00e1cs","year":"2023","journal-title":"Behav Res Methods"},{"issue":"1","key":"pone.0309560.ref074","doi-asserted-by":"crossref","first-page":"17118","DOI":"10.1038\/s41598-021-94488-8","article-title":"In-silico design of envelope based multi-epitope vaccine candidate against Kyasanur forest disease virus","volume":"11","author":"S Arumugam","year":"2021","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0309560.ref075","doi-asserted-by":"crossref","first-page":"108","DOI":"10.2144\/btn-2020-0038","article-title":"Discovery of alliin as a putative inhibitor of the main protease of SARS-CoV-2 by molecular docking","volume":"69","author":"B Cheng","year":"2020","journal-title":"Biotechniques"},{"key":"pone.0309560.ref076","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/978-1-0716-3222-2_16","article-title":"Molecular Dynamics Simulation of Protein Cages","volume":"2671","author":"C Lu","year":"2023","journal-title":"Methods Mol Biol"},{"issue":"12","key":"pone.0309560.ref077","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1007\/s43630-023-00486-2","article-title":"Application of molecular dynamic simulations in modeling the excited state behavior of confined molecules","volume":"22","author":"D Khadka","year":"2023","journal-title":"Photochem Photobiol Sci"},{"issue":"6","key":"pone.0309560.ref078","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1021\/acsptsci.0c00139","article-title":"Vaccine Formulation and Optimization for Human Herpes Virus-5 through an Immunoinformatics Framework","volume":"3","author":"N Kumar","year":"2020","journal-title":"ACS Pharmacol Transl Sci"},{"issue":"6","key":"pone.0309560.ref079","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00251-021-01228-3","article-title":"A reverse vaccinology and immunoinformatics approach for designing a multiepitope vaccine against SARS-CoV-2","volume":"73","author":"E Jahangirian","year":"2021","journal-title":"Immunogenetics"},{"issue":"1","key":"pone.0309560.ref080","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12864-021-07370-2","article-title":"GCSscore: an R package for differential gene expression analysis in Affymetrix\/Thermo-Fisher whole transcriptome microarrays","volume":"22","author":"GM Harris","year":"2021","journal-title":"BMC Genomics"},{"key":"pone.0309560.ref081","doi-asserted-by":"crossref","first-page":"e2020073","DOI":"10.4178\/epih.e2020073","article-title":"Neglected paths of transmission of milkborne brucellosis and tuberculosis in developing countries: novel control opportunities","volume":"42","author":"AAP Milton","year":"2020","journal-title":"Epidemiol Health"},{"issue":"2","key":"pone.0309560.ref082","article-title":"Proteome-Wide Screening of Potential Vaccine Targets against Brucella melitensis","volume":"11","author":"M Malik","year":"2023","journal-title":"Vaccines (Basel)"},{"issue":"Pt 2","key":"pone.0309560.ref083","doi-asserted-by":"crossref","first-page":"131517","DOI":"10.1016\/j.ijbiomac.2024.131517","article-title":"In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches","volume":"267","author":"S Ahmad","year":"2024","journal-title":"Int J Biol Macromol"},{"issue":"4","key":"pone.0309560.ref084","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1080\/21645515.2018.1549449","article-title":"Immunogenicity and safety following primary and booster vaccination with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b vaccine: a randomized trial in the United States","volume":"15","author":"NP Klein","year":"2019","journal-title":"Hum Vaccin Immunother"},{"key":"pone.0309560.ref085","article-title":"An In Silico Multi-epitopes Vaccine Ensemble and Characterization Against Nosocomial Proteus penneri","author":"A Ullah","year":"2023","journal-title":"Mol Biotechnol"},{"issue":"3","key":"pone.0309560.ref086","doi-asserted-by":"crossref","first-page":"274","DOI":"10.2174\/1573409919666230612125440","article-title":"Designing a Multi-epitope Vaccine against the SARS-CoV-2 Variant based on an Immunoinformatics Approach","volume":"20","author":"I Farhani","year":"2024","journal-title":"Curr Comput Aided Drug Des"},{"key":"pone.0309560.ref087","doi-asserted-by":"crossref","first-page":"104388","DOI":"10.1016\/j.meegid.2020.104388","article-title":"In silico designing of peptide based vaccine for Hepatitis viruses using reverse vaccinology approach","volume":"84","author":"D Chaudhuri","year":"2020","journal-title":"Infect Genet Evol"},{"key":"pone.0309560.ref088","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/07391102.2023.2258403","article-title":"Computational design of a multi-epitope vaccine candidate against Langya henipavirus using surface proteins","author":"S Ahmad","year":"2023","journal-title":"J Biomol Struct Dyn"},{"issue":"2","key":"pone.0309560.ref089","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1089\/mdr.2020.0161","article-title":"A Comparative Genomics Approach for Shortlisting Broad-Spectrum Drug Targets in Nontuberculous Mycobacteria","volume":"27","author":"A Swain","year":"2021","journal-title":"Microb Drug Resist"},{"issue":"3","key":"pone.0309560.ref090","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/tbed.12826","article-title":"Seroprevalence of brucellosis in goats and sheep in Thailand: Results from the Thai National Brucellosis Surveillance System from 2013 to 2015","volume":"65","author":"ME Peck","year":"2018","journal-title":"Transbound Emerg Dis"},{"issue":"1","key":"pone.0309560.ref091","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/s41598-017-00720-9","article-title":"Mycobacterium tuberculosis Lineage Distribution in Xinjiang and Gansu Provinces, China","volume":"7","author":"H Chen","year":"2017","journal-title":"Sci Rep"},{"issue":"11","key":"pone.0309560.ref092","article-title":"Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach","volume":"9","author":"AU Haq","year":"2021","journal-title":"Vaccines (Basel)"},{"issue":"1","key":"pone.0309560.ref093","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s43141-021-00199-y","article-title":"Screening and characterization of hypothetical proteins of Plasmodium falciparum as novel vaccine candidates in the fight against malaria using reverse vaccinology","volume":"19","author":"C Aguttu","year":"2021","journal-title":"J Genet Eng Biotechnol"},{"key":"pone.0309560.ref094","doi-asserted-by":"crossref","first-page":"768569","DOI":"10.3389\/fimmu.2022.768569","article-title":"A Systematic Immuno-Informatic Approach to Design a Multiepitope-Based Vaccine Against Emerging Multiple Drug Resistant Serratia marcescens","volume":"13","author":"MSF Damas","year":"2022","journal-title":"Front Immunol"},{"key":"pone.0309560.ref095","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.3389\/fimmu.2019.02181","article-title":"Bacterial RNA Contributes to the Down-Modulation of MHC-II Expression on Monocytes\/Macrophages Diminishing CD4(+) T Cell Responses","volume":"10","author":"MA Milillo","year":"2019","journal-title":"Front Immunol"},{"issue":"23","key":"pone.0309560.ref096","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222312814","article-title":"Pan-Genome Reverse Vaccinology Approach for the Design of Multi-Epitope Vaccine Construct against Escherichia albertii","volume":"22","author":"K Jalal","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pone.0309560.ref097","doi-asserted-by":"crossref","first-page":"104420","DOI":"10.1016\/j.compbiomed.2021.104420","article-title":"Immunogenomics guided design of immunomodulatory multi-epitope subunit vaccine against the SARS-CoV-2 new variants, and its validation through in silico cloning and immune simulation","volume":"133","author":"A Khan","year":"2021","journal-title":"Comput Biol Med"},{"issue":"10","key":"pone.0309560.ref098","article-title":"Designing a Multi-Epitope Vaccine against Chlamydia trachomatis by Employing Integrated Core Proteomics, Immuno-Informatics and In Silico Approaches","volume":"10","author":"S Aslam","year":"2021","journal-title":"Biology (Basel)"},{"issue":"1","key":"pone.0309560.ref099","doi-asserted-by":"crossref","first-page":"7757","DOI":"10.1038\/s41598-022-11851-z","article-title":"Designing a novel multi\u2011epitope vaccine against Ebola virus using reverse vaccinology approach","volume":"12","author":"M Alizadeh","year":"2022","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0309560.ref100","doi-asserted-by":"crossref","first-page":"13836","DOI":"10.1038\/s41598-021-93266-w","article-title":"An immunoinformatics approach to design a multi-epitope vaccine against Mycobacterium tuberculosis exploiting secreted exosome proteins","volume":"11","author":"R Sharma","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0309560.ref101","doi-asserted-by":"crossref","first-page":"735373","DOI":"10.3389\/fimmu.2021.735373","article-title":"Immunoinformatics-Based Designing of a Multi-Epitope Chimeric Vaccine From Multi-Domain Outer Surface Antigens of Leptospira","volume":"12","author":"P Kumar","year":"2021","journal-title":"Front Immunol"},{"issue":"4","key":"pone.0309560.ref102","first-page":"e22252","article-title":"Immmunoinformatics-based design of a multi-epitope vaccine with CTLA-4 extracellular domain to combat Helicobacter pylori","volume":"36","author":"Z Ru","year":"2022","journal-title":"Faseb j"},{"issue":"5","key":"pone.0309560.ref103","article-title":"Preliminary Work Towards Finding Proteins as Potential Vaccine Candidates for Vibrio cholerae Pakistani Isolates through Reverse Vaccinology","volume":"55","author":"S Zeb","year":"2019","journal-title":"Medicina (Kaunas)"},{"issue":"1","key":"pone.0309560.ref104","doi-asserted-by":"crossref","first-page":"15431","DOI":"10.1038\/s41598-021-92176-1","article-title":"Designing a multi-epitope vaccine candidate to combat MERS-CoV by employing an immunoinformatics approach","volume":"11","author":"S Mahmud","year":"2021","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0309560.ref105","doi-asserted-by":"crossref","first-page":"8736","DOI":"10.1038\/s41598-022-12651-1","article-title":"In silico design and analyses of a multi-epitope vaccine against Crimean-Congo hemorrhagic fever virus through reverse vaccinology and immunoinformatics approaches","volume":"12","author":"AA Omoniyi","year":"2022","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0309560.ref106","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41590-017-0006-x","article-title":"The twilight of immunity: emerging concepts in aging of the immune system","volume":"19","author":"J. Nikolich-\u017dugich","year":"2018","journal-title":"Nat Immunol"},{"issue":"1","key":"pone.0309560.ref107","doi-asserted-by":"crossref","first-page":"9044","DOI":"10.1038\/s41598-018-26689-7","article-title":"Subtractive proteomics to identify novel drug targets and reverse vaccinology for the development of chimeric vaccine against Acinetobacter baumannii","volume":"8","author":"V Solanki","year":"2018","journal-title":"Sci Rep"},{"key":"pone.0309560.ref108","doi-asserted-by":"crossref","first-page":"1115345","DOI":"10.3389\/fimmu.2023.1115345","article-title":"Design of a multi-epitopic vaccine against Epstein-Barr virus via computer-based methods","volume":"14","author":"A Larijani","year":"2023","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0309560.ref109","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1080\/07391102.2020.1792347","article-title":"Designing a multi-epitope vaccine against SARS-CoV-2: an immunoinformatics approach","volume":"40","author":"A Samad","year":"2022","journal-title":"J Biomol Struct Dyn"},{"issue":"5","key":"pone.0309560.ref110","doi-asserted-by":"crossref","first-page":"322","DOI":"10.2174\/1570162X17666190102151717","article-title":"In Silico Design and Immunologic Evaluation of HIV-1 p24-Nef Fusion Protein to Approach a Therapeutic Vaccine Candidate","volume":"16","author":"MS Larijani","year":"2018","journal-title":"Curr HIV Res"},{"issue":"7","key":"pone.0309560.ref111","doi-asserted-by":"crossref","first-page":"5373","DOI":"10.1021\/acs.jmedchem.3c01840","article-title":"Chimeric NOD2 Mincle Agonists as Vaccine Adjuvants","volume":"67","author":"EM Dangerfield","year":"2024","journal-title":"J Med Chem"},{"key":"pone.0309560.ref112","doi-asserted-by":"crossref","first-page":"19081","DOI":"10.1038\/srep19081","article-title":"Changes in pathogenicity and immunogenicity of Mycoplasma mycoides subsp. mycoides strains revealed by comparative genomics analysis","volume":"6","author":"Y Li","year":"2016","journal-title":"Sci Rep"},{"issue":"5999","key":"pone.0309560.ref113","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1126\/science.1191996","article-title":"Stability of the regulatory T cell lineage in vivo","volume":"329","author":"YP Rubtsov","year":"2010","journal-title":"Science"},{"issue":"29","key":"pone.0309560.ref114","doi-asserted-by":"crossref","first-page":"18103","DOI":"10.1039\/D1RA02885E","article-title":"Immunoinformatics-guided design of a multi-epitope vaccine based on the structural proteins of severe acute respiratory syndrome coronavirus 2","volume":"11","author":"AJ Obaidullah","year":"2021","journal-title":"RSC Adv"},{"issue":"9\u201310","key":"pone.0309560.ref115","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s00239-021-10027-z","article-title":"Codon Usage Bias: An Endless Tale","volume":"89","author":"A Iriarte","year":"2021","journal-title":"J Mol Evol"},{"issue":"5","key":"pone.0309560.ref116","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/dnares\/dsu017","article-title":"Modelling the efficiency of codon-tRNA interactions based on codon usage bias","volume":"21","author":"R Sabi","year":"2014","journal-title":"DNA Res"},{"issue":"2","key":"pone.0309560.ref117","article-title":"Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate against Onchocerciasis and Related Filarial Diseases","volume":"10","author":"RA Shey","year":"2021","journal-title":"Pathogens"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0309560","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T17:27:13Z","timestamp":1730136433000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0309560"}},"subtitle":[],"editor":[{"given":"Wenping","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,10,28]]},"references-count":117,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0309560","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,28]]}}}