{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:45:32Z","timestamp":1780321532573,"version":"3.54.1"},"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for the Support of Scientific and Technological Development of the State of Cear\u00c3\u00a1","award":["PVS0215000420100 23"],"award-info":[{"award-number":["PVS0215000420100 23"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Tularemia is an extremely contagious zoonotic illness resulting from infection with the intracellular bacterium\n                    <jats:italic>Francisella tularensis<\/jats:italic>\n                    . It is transmitted primarily via vector bites particularly from ticks, flies, and mosquitoes and is a severe public health threat. Because of its high virulence, low infective dose, aerosol transmissibility, and potential for mass casualties,\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    is also considered a potential biological warfare agent. Despite its severity, there is presently no licensed vaccine against this pathogen. In the present work, a subtractive proteomics pipeline was implemented to identify potential antigenic targets to prepare a multi-epitope vaccine. Five vaccine constructs were generated through the combination of B-cell, HTL, and CTL epitopes with suitable adjuvants and linkers. Among these, two constructs V1 and V2 were extremely non-allergenic and antigenic. To assess immune receptor engagement, molecular docking was conducted with TLR4 and TLR5, followed by 200 ns molecular dynamics simulations. Vaccine-receptor complexes were analyzed using RMSD, RMSF, radius of gyration (Rg), Dynamic Cross-Correlation Matrix (DCCM), SASA, PCA, H-bond analysis and MMPBSA binding energy calculations, all confirming structural stability and strong binding affinity.\n                    <jats:italic>In-silico<\/jats:italic>\n                    cloning revealed a GC content of 50% and 1.0 codon adaptation index (CAI), suggesting high expression potential in\n                    <jats:italic>E. coli<\/jats:italic>\n                    . Immune simulation further supported the construct`s ability to elicit a robust and long-lasting immunity. These computational findings highlight the potential of the constructed vaccines as effective candidates against\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    , though experimental substantiation is requisite.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0337692","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T18:34:45Z","timestamp":1766774085000},"page":"e0337692","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["In-silico core proteome analysis for chimeric vaccine development against tick-borne tularemia"],"prefix":"10.1371","volume":"20","author":[{"given":"Bader S.","family":"Alotaibi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatiha","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Bilal Iqbal","family":"Rehmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fizza","family":"Arshad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Umer","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umar","family":"Nishan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abid","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled Fahmi","family":"Fawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Altwaim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed M. N.","family":"Alasmari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Dib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6126-7102","authenticated-orcid":true,"given":"Mohibullah","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"issue":"4","key":"pone.0337692.ref001","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a010314","article-title":"Mechanisms of Francisella tularensis intracellular pathogenesis","volume":"3","author":"J Celli","year":"2013","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"4","key":"pone.0337692.ref002","doi-asserted-by":"crossref","first-page":"905","DOI":"10.3390\/microorganisms11040905","article-title":"Identification of francisella tularensis subspecies in a clinical setting using MALDI-TOF MS: an in-house francisella library and biomarkers","volume":"11","author":"MC de Vries","year":"2023","journal-title":"Microorganisms"},{"issue":"1","key":"pone.0337692.ref003","doi-asserted-by":"crossref","first-page":"2274638","DOI":"10.1080\/21505594.2023.2274638","article-title":"Pathogenicity and virulence of Francisella tularensis","volume":"14","author":"M Degabriel","year":"2023","journal-title":"Virulence"},{"issue":"10","key":"pone.0337692.ref004","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/cir612","article-title":"Human tularemia in France, 2006-2010","volume":"53","author":"M Maurin","year":"2011","journal-title":"Clin Infect Dis"},{"key":"pone.0337692.ref005","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fcimb.2014.00035","article-title":"Comparative review of Francisella tularensis and Francisella novicida","volume":"4","author":"LC Kingry","year":"2014","journal-title":"Front Cell Infect Microbiol"},{"issue":"21","key":"pone.0337692.ref006","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1001\/jama.285.21.2763","article-title":"Tularemia as a biological weapon: medical and public health management","volume":"285","author":"DT Dennis","year":"2001","journal-title":"JAMA"},{"key":"pone.0337692.ref007","author":"WL Jellison","year":"1955"},{"issue":"1","key":"pone.0337692.ref008","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/inf.1971.3.issue-1.02","article-title":"Airborne tularemia in Sweden","volume":"3","author":"S Dahlstrand","year":"1971","journal-title":"Scand J Infect Dis"},{"key":"pone.0337692.ref009","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1749-6632.1992.tb38021.x","article-title":"Japanese biological warfare research on humans: a case study of microbiology and ethics","volume":"666","author":"S Harris","year":"1992","journal-title":"Ann N Y Acad Sci"},{"key":"pone.0337692.ref010","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fcimb.2014.00040","article-title":"New therapeutic approaches for treatment of tularaemia: a review","volume":"4","author":"S Boisset","year":"2014","journal-title":"Front Cell Infect Microbiol"},{"issue":"2","key":"pone.0337692.ref011","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1586\/14787210.2015.986463","article-title":"Francisella tularensis as a potential agent of bioterrorism?","volume":"13","author":"M Maurin","year":"2015","journal-title":"Expert Rev Anti Infect Ther"},{"issue":"1","key":"pone.0337692.ref012","doi-asserted-by":"crossref","first-page":"13321","DOI":"10.1038\/s41598-019-49354-z","article-title":"Immunoinformatics approaches to explore Helicobacter Pylori proteome (Virulence Factors) to design B and T cell multi-epitope subunit vaccine","volume":"9","author":"M Khan","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0337692.ref013","doi-asserted-by":"crossref","first-page":"126002","DOI":"10.1016\/j.ijbiomac.2023.126002","article-title":"Targeted vaccine development against Bilophila wadsworthia to curb colon diseases: A multiepitope approach based on reverse vaccinology and computational analysis","volume":"250","author":"S Khan","year":"2023","journal-title":"Int J Biol Macromol"},{"key":"pone.0337692.ref014","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2023.1017315","article-title":"Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets","volume":"13","author":"A Qasim","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0337692.ref015","doi-asserted-by":"crossref","first-page":"104701","DOI":"10.1016\/j.compbiomed.2021.104701","article-title":"Chlamydia trachomatis core genome data mining for promising novel drug targets and chimeric vaccine candidates identification","volume":"136","author":"M Aslam","year":"2021","journal-title":"Comput Biol Med"},{"key":"pone.0337692.ref016","article-title":"VFDB 2019: a comparative pathogenomic platform with an interactive web interface","volume":"47","author":"B Liu","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pone.0337692.ref017","doi-asserted-by":"crossref","first-page":"971263","DOI":"10.3389\/fmicb.2022.971263","article-title":"Multi-epitope chimeric vaccine designing and novel drug targets prioritization against multi-drug resistant Staphylococcus pseudintermedius","volume":"13","author":"S Jaan","year":"2022","journal-title":"Front Microbiol"},{"key":"pone.0337692.ref018","article-title":"DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements","volume":"42","author":"H Luo","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"pone.0337692.ref019","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkm321","article-title":"KAAS: an automatic genome annotation and pathway reconstruction server","volume":"35","author":"Y Moriya","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"pone.0337692.ref020","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1471-2105-8-4","article-title":"VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines","volume":"8","author":"IA Doytchinova","year":"2007","journal-title":"BMC Bioinformatics"},{"issue":"6","key":"pone.0337692.ref021","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v.2--a server for in silico prediction of allergens","volume":"20","author":"I Dimitrov","year":"2014","journal-title":"J Mol Model"},{"issue":"5","key":"pone.0337692.ref022","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1006\/cbir.1999.0355","article-title":"Book reviews","volume":"23","author":"P Cash","year":"1999","journal-title":"Cell Biology International"},{"key":"pone.0337692.ref023","doi-asserted-by":"crossref","first-page":"108056","DOI":"10.1016\/j.compbiomed.2024.108056","article-title":"Immunoinformatics-driven In silico vaccine design for Nipah virus (NPV): Integrating machine learning and computational epitope prediction","volume":"170","author":"M Shahab","year":"2024","journal-title":"Comput Biol Med"},{"key":"pone.0337692.ref024","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3389\/fimmu.2017.00278","article-title":"The immune epitope database and analysis resource in epitope discovery and synthetic vaccine design","volume":"8","author":"W Fleri","year":"2017","journal-title":"Front Immunol"},{"issue":"5","key":"pone.0337692.ref025","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1182\/blood-2008-05-078154","article-title":"CD4 T cells: fates, functions, and faults","volume":"112","author":"J Zhu","year":"2008","journal-title":"Blood"},{"key":"pone.0337692.ref026","doi-asserted-by":"crossref","first-page":"105507","DOI":"10.1016\/j.compbiomed.2022.105507","article-title":"Designing a multi-epitope vaccine against Chlamydia pneumoniae by integrating the core proteomics, subtractive proteomics and reverse vaccinology-based immunoinformatics approaches","volume":"145","author":"F Noor","year":"2022","journal-title":"Comput Biol Med"},{"issue":"3","key":"pone.0337692.ref027","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3390\/vaccines2030515","article-title":"Peptide vaccine: progress and challenges","volume":"2","author":"W Li","year":"2014","journal-title":"Vaccines (Basel)"},{"key":"pone.0337692.ref028","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jtbi.2014.01.018","article-title":"A novel multi-epitope peptide vaccine against cancer: an in silico approach","volume":"349","author":"N Nezafat","year":"2014","journal-title":"J Theor Biol"},{"key":"pone.0337692.ref029","doi-asserted-by":"crossref","first-page":"104795","DOI":"10.1016\/j.meegid.2021.104795","article-title":"Rational design of multimeric based subunit vaccine against Mycoplasma pneumonia: Subtractive proteomics with immunoinformatics framework","volume":"91","author":"M Mahmood","year":"2021","journal-title":"Infect Genet Evol"},{"key":"pone.0337692.ref030","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1385\/1-59259-890-0:571","article-title":"Protein Identification and Analysis Tools on the ExPASy Server","volume-title":"The Proteomics Protocols Handbook","author":"E Gasteiger","year":"2005"},{"issue":"17","key":"pone.0337692.ref031","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1093\/bioinformatics\/btp386","article-title":"SOLpro: accurate sequence-based prediction of protein solubility","volume":"25","author":"CN Magnan","year":"2009","journal-title":"Bioinformatics"},{"issue":"6","key":"pone.0337692.ref032","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/bioinformatics\/11.6.681","article-title":"SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments","volume":"11","author":"C Geourjon","year":"1995","journal-title":"Bioinformatics"},{"issue":"4","key":"pone.0337692.ref033","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/bioinformatics\/16.4.404","article-title":"The PSIPRED protein structure prediction server","volume":"16","author":"LJ McGuffin","year":"2000","journal-title":"Bioinformatics"},{"issue":"12","key":"pone.0337692.ref034","doi-asserted-by":"crossref","first-page":"5634","DOI":"10.1038\/s41596-021-00628-9","article-title":"The trRosetta server for fast and accurate protein structure prediction","volume":"16","author":"Z Du","year":"2021","journal-title":"Nat Protoc"},{"key":"pone.0337692.ref035","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1142\/9789814449144_0005","article-title":"The Ramachandran plot and protein structure validation","volume-title":"Biomolecular forms and functions","author":"RA Laskowski","year":"2013"},{"issue":"1","key":"pone.0337692.ref036","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jmb.2004.06.088","article-title":"A comparative study of the relationship between protein structure and beta-aggregation in globular and intrinsically disordered proteins","volume":"342","author":"R Linding","year":"2004","journal-title":"J Mol Biol"},{"key":"pone.0337692.ref037","doi-asserted-by":"crossref","first-page":"110869","DOI":"10.1016\/j.vetimm.2024.110869","article-title":"Peptide-based vaccine design against Hendra virus through immunoinformatics approach","volume":"280","author":"A Sarfraz","year":"2025","journal-title":"Vet Immunol Immunopathol"},{"issue":"6","key":"pone.0337692.ref038","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1002\/pmic.200300771","article-title":"Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence","volume":"4","author":"N Blom","year":"2004","journal-title":"Proteomics"},{"key":"pone.0337692.ref039","doi-asserted-by":"crossref","first-page":"151186","DOI":"10.1016\/j.ejcb.2021.151186","article-title":"Advances in understanding N-glycosylation structure, function, and regulation in health and disease","volume":"100","author":"S Esmail","year":"2021","journal-title":"Eur J Cell Biol"},{"key":"pone.0337692.ref040","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1186\/1471-2105-9-514","article-title":"ElliPro: a new structure-based tool for the prediction of antibody epitopes","volume":"9","author":"J Ponomarenko","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"pone.0337692.ref041","doi-asserted-by":"crossref","first-page":"1322712","DOI":"10.3389\/fimmu.2024.1322712","article-title":"DiscoTope-3.0: improved B-cell epitope prediction using inverse folding latent representations","volume":"15","author":"MH H\u00f8ie","year":"2024","journal-title":"Front Immunol"},{"key":"pone.0337692.ref042","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gky473","article-title":"CASTp 3.0: computed atlas of surface topography of proteins","volume":"46","author":"W Tian","year":"2018","journal-title":"Nucleic Acids Research"},{"key":"pone.0337692.ref043","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jtbi.2014.01.018","article-title":"A novel multi-epitope peptide vaccine against cancer: An in silico approach","volume":"349","author":"N Nezafat","year":"2014","journal-title":"Journal of Theoretical Biology"},{"issue":"2","key":"pone.0337692.ref044","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s12026-023-09429-6","article-title":"Rational design of multi-epitope-based vaccine by exploring all dengue virus serotypes proteome: an immunoinformatic approach","volume":"72","author":"AA Alsaiari","year":"2024","journal-title":"Immunol Res"},{"key":"pone.0337692.ref045","doi-asserted-by":"crossref","first-page":"108003","DOI":"10.1016\/j.compbiolchem.2023.108003","article-title":"Integrated computational approaches for designing potent pyrimidine-based CDK9 inhibitors: 3D-QSAR, docking, and molecular dynamics simulations","volume":"108","author":"I Habib","year":"2024","journal-title":"Comput Biol Chem"},{"key":"pone.0337692.ref046","doi-asserted-by":"crossref","first-page":"1395870","DOI":"10.3389\/fimmu.2024.1395870","article-title":"Immunoinformatics assisted profiling of West Nile virus proteome to determine immunodominant epitopes for the development of next-generation multi-peptide vaccine","volume":"15","author":"A Karkashan","year":"2024","journal-title":"Front Immunol"},{"issue":"14","key":"pone.0337692.ref047","doi-asserted-by":"crossref","first-page":"6477","DOI":"10.1080\/07391102.2021.1886171","article-title":"Whole proteome screening and identification of potential epitopes of SARS-CoV-2 for vaccine design-an immunoinformatic, molecular docking and molecular dynamics simulation accelerated robust strategy","volume":"40","author":"MMA Ezaj","year":"2022","journal-title":"J Biomol Struct Dyn"},{"issue":"1","key":"pone.0337692.ref048","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1039\/C5MB00630A","article-title":"Molecular simulation studies on the binding selectivity of 2-anilino-4-(thiazol-5-yl)-pyrimidines in complexes with CDK2 and CDK7","volume":"12","author":"TA Chohan","year":"2016","journal-title":"Mol Biosyst"},{"key":"pone.0337692.ref049","doi-asserted-by":"crossref","first-page":"1402963","DOI":"10.3389\/fmicb.2024.1402963","article-title":"Epitope screening and self-assembled nanovaccine molecule design of PDCoV-S protein based on immunoinformatics","volume":"15","author":"Y Chen","year":"2024","journal-title":"Front Microbiol"},{"key":"pone.0337692.ref050","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gki376","article-title":"JCat: a novel tool to adapt codon usage of a target gene to its potential expression host","volume":"33","author":"A Grote","year":"2005","journal-title":"Nucleic Acids Research"},{"issue":"14","key":"pone.0337692.ref051","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1093\/bioinformatics\/btr335","article-title":"Immune system simulation online","volume":"27","author":"N Rapin","year":"2011","journal-title":"Bioinformatics"},{"key":"pone.0337692.ref052","doi-asserted-by":"crossref","first-page":"6718083","DOI":"10.1155\/2018\/6718083","article-title":"Immunoinformatics approach for epitope-based peptide vaccine design and active site prediction against polyprotein of emerging oropouche virus","volume":"2018","author":"UK Adhikari","year":"2018","journal-title":"J Immunol Res"},{"key":"pone.0337692.ref053","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/1471-2105-7-153","article-title":"Predicting population coverage of T-cell epitope-based diagnostics and vaccines","volume":"7","author":"H-H Bui","year":"2006","journal-title":"BMC Bioinformatics"},{"issue":"11","key":"pone.0337692.ref054","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e31304","article-title":"Subtractive proteomics-based vaccine targets annotation and reverse vaccinology approaches to identify multiepitope vaccine against Plesiomonas shigelloides","volume":"10","author":"D Rasool","year":"2024","journal-title":"Heliyon"},{"issue":"3","key":"pone.0337692.ref055","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1080\/21645515.2015.1012017","article-title":"In silico design of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations","volume":"11","author":"Y Yang","year":"2015","journal-title":"Hum Vaccin Immunother"},{"key":"pone.0337692.ref056","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1016\/j.vaccine.2005.01.031","article-title":"An ingenious design for peptide vaccines","volume":"23","author":"A Yano","year":"2005","journal-title":"Vaccine"},{"issue":"6","key":"pone.0337692.ref057","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1159\/000445059","article-title":"Design and Evaluation of a Multi-Epitope Peptide of Human Metapneumovirus","volume":"58","author":"X Li","year":"2015","journal-title":"Intervirology"},{"issue":"1","key":"pone.0337692.ref058","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1038\/s41598-024-55372-3","article-title":"Proteomics-based vaccine targets annotation and design of multi-epitope vaccine against antibiotic-resistant Streptococcus gallolyticus","volume":"14","author":"P Chao","year":"2024","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0337692.ref059","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.3390\/biomedinformatics4030088","article-title":"Harnessing immunoinformatics for precision vaccines: designing epitope-based subunit vaccines against Hepatitis E virus","volume":"4","author":"EK Oladipo","year":"2024","journal-title":"BioMedInformatics"},{"issue":"47","key":"pone.0337692.ref060","doi-asserted-by":"crossref","first-page":"18631","DOI":"10.1073\/pnas.0702130104","article-title":"Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2","volume":"104","author":"N Funderburg","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5439","key":"pone.0337692.ref061","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1126\/science.286.5439.525","article-title":"Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6","volume":"286","author":"D Yang","year":"1999","journal-title":"Science"},{"issue":"2","key":"pone.0337692.ref062","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3390\/vaccines12020139","article-title":"Advancing PEDV vaccination: comparison between inactivated and flagellin N-terminus-adjuvanted subunit vaccines","volume":"12","author":"A Murtaza","year":"2024","journal-title":"Vaccines (Basel)"},{"issue":"10","key":"pone.0337692.ref063","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.4049\/jimmunol.1002156","article-title":"Flagellin as an adjuvant: cellular mechanisms and potential","volume":"185","author":"SB Mizel","year":"2010","journal-title":"J Immunol"},{"issue":"1","key":"pone.0337692.ref064","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1385\/IR:33:1:083","article-title":"Effects of flagellin on innate and adaptive immunity","volume":"33","author":"AN Honko","year":"2005","journal-title":"Immunol Res"},{"key":"pone.0337692.ref065","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.cytogfr.2021.01.001","article-title":"Granulocyte macrophage colony-stimulating factor has come of age: From a vaccine adjuvant to antiviral immunotherapy","volume":"59","author":"M Petrina","year":"2021","journal-title":"Cytokine Growth Factor Rev"},{"issue":"6","key":"pone.0337692.ref066","doi-asserted-by":"crossref","first-page":"111162","DOI":"10.1016\/j.humimm.2024.111162","article-title":"Rational design of novel peptide-based vaccine against the emerging OZ virus","volume":"85","author":"F Arshad","year":"2024","journal-title":"Hum Immunol"},{"key":"pone.0337692.ref067","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.3389\/fmicb.2018.02258","article-title":"Heparin-binding hemagglutinin adhesin (HBHA) is involved in intracytosolic lipid inclusions formation in mycobacteria","volume":"9","author":"D Raze","year":"2018","journal-title":"Front Microbiol"},{"issue":"12","key":"pone.0337692.ref068","doi-asserted-by":"crossref","first-page":"6799","DOI":"10.1128\/IAI.72.12.6799-6805.2004","article-title":"The mycobacterial heparin-binding hemagglutinin is a protective antigen in the mouse aerosol challenge model of tuberculosis","volume":"72","author":"M Parra","year":"2004","journal-title":"Infect Immun"},{"issue":"1","key":"pone.0337692.ref069","doi-asserted-by":"crossref","DOI":"10.1186\/s12859-023-05197-0","article-title":"Designing multi-epitope vaccine against important colorectal cancer (CRC) associated pathogens based on immunoinformatics approach","volume":"24","author":"H Motamedi","year":"2023","journal-title":"BMC Bioinformatics"},{"issue":"2","key":"pone.0337692.ref070","first-page":"66","article-title":"In silico Prediction and Docking of Tertiary Structure of LuxI, an Inducer Synthase of Vibrio fischeri","volume":"4","author":"MZS Al-Khayyat","year":"2016","journal-title":"Rep Biochem Mol Biol"},{"issue":"1","key":"pone.0337692.ref071","doi-asserted-by":"crossref","first-page":"107939","DOI":"10.1016\/j.jsb.2023.107939","article-title":"Revisiting the ramachandran plot based on statistical analysis of static and dynamic characteristics of protein structures","volume":"215","author":"SW Park","year":"2023","journal-title":"J Struct Biol"},{"issue":"3","key":"pone.0337692.ref072","first-page":"763","article-title":"Integrating immunoinformatics and computational epitope prediction for a vaccine candidate against respiratory syncytial virus","volume":"9","author":"TL Nguyen","year":"2024","journal-title":"Infect Dis Model"},{"key":"pone.0337692.ref073","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","author":"MJ Abraham","year":"2015","journal-title":"SoftwareX"},{"issue":"5","key":"pone.0337692.ref074","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41579-020-00506-3","article-title":"The role of vaccines in combatting antimicrobial resistance","volume":"19","author":"F Micoli","year":"2021","journal-title":"Nat Rev Microbiol"},{"issue":"7","key":"pone.0337692.ref075","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.3390\/microorganisms12071270","article-title":"Immunoinformatics and reverse vaccinology approach for the identification of potential vaccine candidates against vandammella animalimors","volume":"12","author":"A Hasan","year":"2024","journal-title":"Microorganisms"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0337692","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T18:34:57Z","timestamp":1766774097000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0337692"}},"subtitle":[],"editor":[{"given":"Sheikh Arslan","family":"Sehgal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":75,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0337692","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]}}}