{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:16:08Z","timestamp":1792682168602,"version":"4.5.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP2024R45"],"award-info":[{"award-number":["RSP2024R45"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Opisthorchis viverrini<\/jats:italic> is the etiological agent of the disease opisthorchiasis and related cholangiocarcinoma (CCA). It infects fish-eating mammals and more than 10 million people in Southeast Asia suffered from opisthorchiasis with a high fatality rate. The only effective drug against this parasite is Praziquantel, which has significant side effects. Due to the lack of appropriate treatment options and the high death rate, there is a dire need to develop novel therapies against this pathogen. In this study, we designed a multi-epitope chimeric vaccine design against <jats:italic>O. viverrini<\/jats:italic> by using immunoinformatics approaches. Non-allergenic and immunogenic MHC-1, MHC-2, and B cell epitopes of three candidate proteins thioredoxin peroxidase (<jats:italic>Ov-TPx-1<\/jats:italic>), cathepsin F1 (<jats:italic>Ov-CF-1<\/jats:italic>) and calreticulin (<jats:italic>Ov-CALR<\/jats:italic>) of <jats:italic>O. viverrini<\/jats:italic>, were predicted to construct a potent multiepitope vaccine. The coverage of the HLA-alleles of these selected epitopes was determined globally. Four vaccine constructs made by different adjuvants and linkers were evaluated in the context of their physicochemical properties, antigenicity, and allergenicity. Protein-protein docking and MD simulation found that vaccines 3 was more stable and had a higher binding affinity for TLR2 and TLR4 immune receptors. <jats:italic>In-silico<\/jats:italic> restriction cloning of vaccine model led to the formation of plasmid constructs for expression in a suitable host. Finally, the immune simulation showed strong immunological reactions to the engineered vaccine. These findings suggest that the final vaccine construct has the potential to be validated by <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> experiments to confirm its efficacy against the CCA causing <jats:italic>O. viverrini<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1281544","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T04:45:28Z","timestamp":1720586728000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Development of a subunit vaccine against the cholangiocarcinoma causing Opisthorchis viverrini: a computational approach"],"prefix":"10.3389","volume":"15","author":[{"given":"Mohibullah","family":"Shah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farva","family":"Sitara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asifa","family":"Sarfraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Shehroz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tehreem Ul","family":"Wara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asia","family":"Perveen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najeeb","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aqal","family":"Zaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umar","family":"Nishan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarfraz","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riaz","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Essam A.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvash Chandra","family":"Ojha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2013.07.007","article-title":"The zoonotic, fish-borne liver flukes Clonorchis sinensis, Opisthorchis felineus and Opisthorchis viverrini","volume":"43","author":"Petney","year":"2013","journal-title":"Int J Parasitol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2174\/187152610793180902","article-title":"Opisthorchiidosis-A review","volume":"10","author":"Schuster R","year":"2010","journal-title":"Infect Disord Drug Targets"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2020.10.024","article-title":"Foodborne zoonotic parasites of the family Opisthorchiidae","volume":"135","author":"Saijuntha","year":"2021","journal-title":"Res Vet Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/0020-7519(86)90091-3","article-title":"Field studies on the transmission of the human liver fluke, Opisthorchis viverrini, in northeast Thailand: population changes of the snail intermediate host","volume":"16","author":"Brockelman","year":"1986","journal-title":"Int J Parasitol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2003.02.001","article-title":"Epidemiology of opisthorchis viverrini","volume":"88","author":"Sithithaworn","year":"2003","journal-title":"Acta Trop"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4378","DOI":"10.1038\/ncomms5378","article-title":"The Opisthorchis viverrini genome provides insights into life in the bile duct","volume":"5","author":"Young","year":"2014","journal-title":"Nat Commun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1039\/c0mb00295j.Infection","article-title":"NIH public access","volume":"7","author":"Smout","year":"2013","journal-title":"Molecular Systems"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s13149-017-0544-8","article-title":"Vaincre la distomatose \u00e0 Opisthorchis viverrini pour pr\u00e9venir le cholangiocarcinome Control of Opisthorchis viverrini infection for cholangiocarcinoma prevention","volume":"110","author":"Buisson","year":"2017","journal-title":"Bulletin de la Soci\u00e9t\u00e9 de pathologie exotique"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.47102\/annals-acadmedsg.","article-title":"Letter to the editor oriental liver fluke infestation presenting more than 50 years after immigration","volume":"38","author":"Editor","year":"2009","journal-title":"Ann Acad Med"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1016\/bs.apar.2018.08.003","volume-title":"Immune Response to Opisthorchis viverrini Infection and Its Role in Pathology","author":"Sripa","year":"2018"},{"key":"B11","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.actatropica.2019.05.011","article-title":"A comprehensive review of omics and host-parasite interplays studies, towards control of Opisthorchis viverrini infection for prevention of cholangiocarcinoma","volume":"196","author":"Prasopdee","year":"2019","journal-title":"Acta Trop"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000611","article-title":"A granulin-like growth factor secreted by the carcinogenic liver fluke, opisthorchis viverrini, promotes proliferation of host cells","volume":"5","author":"Smout","year":"2009","journal-title":"PLoS Pathog"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv291","article-title":"Carcinogenic liver fluke secretes extracellular vesicles that promote cholangiocytes to adopt a tumorigenic phenotype","volume":"212","author":"Chaiyadet","year":"2015","journal-title":"J Infect Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw785","article-title":"Efficacy and safety of praziquantel against light infections of opisthorchis viverrini: A randomized parallel single-blind dose-ranging trial","volume":"64","author":"Sayasone","year":"2017","journal-title":"Clin Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001726","article-title":"Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: A randomized, single-blinded dose-comparison trial","volume":"6","author":"Lovis","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s40249-019-0529-5","article-title":"Repeated praziquantel treatment and Opisthorchis viverrini infection: a population-based cross-sectional study in northeast Thailand","volume":"8","author":"Thinkhamrop","year":"2019","journal-title":"Infect Dis Poverty"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.5604\/01.3001.0012.3140","article-title":"Association between repeated praziquantel treatment and papillary, and intrahepatic cholangiocarcinoma","volume":"17","author":"Luvira","year":"2018","journal-title":"Ann Hepatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2021.105850","article-title":"Acta Tropica Investigation of possible alternate animal reservoir hosts of Opisthorchis viverrini","volume":"217","author":"Tangkawattana","year":"2021","journal-title":"Acta Trop"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2020.105355","article-title":"Laha T. Partial protection with a chimeric tetraspanin-leucine aminopeptidase subunit vaccine against Opisthorchis viverrini infection in hamsters","volume":"204","author":"Thi Phung","year":"2020","journal-title":"Acta Trop"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9070740","article-title":"Monoclonal antibodies targeting an opisthorchis viverrini extracellular vesicle tetraspanin protect hamsters against challenge infection","volume":"9","author":"Phumrattanaprapin","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007450","article-title":"Vaccination of hamsters with Opisthorchis viverrini extracellular vesicles and vesicle-derived recombinant tetraspanins induces antibodies that block vesicle uptake by cholangiocytes and reduce parasite burden after challenge infection","volume":"13","author":"Chaiyadet","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1016\/bs.apar.2018.06.002","volume-title":"Opisthorchis viverrini Proteome and Host e Parasite Interactions","author":"Suttiprapa","year":"2018"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2018.08.009","article-title":"Acta Tropica Evaluation of Opisthorchis viverrini calreticulin for potential host modulation","volume":"187","author":"Chaibangyang","year":"2018","journal-title":"Acta Trop"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1259612","article-title":"Vaccinomics-based next-generation multi-epitope chimeric vaccine models prediction against Leishmania tropica - a hierarchical subtractive proteomics and immunoinformatics approach","volume":"14","author":"Aiman","year":"2023","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1284621","article-title":"Structural informatics approach for designing an epitope-based vaccine against the brain-eating Naegleria fowleri","volume":"14","author":"Sarfraz","year":"2023","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","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":"Doytchinova","year":"2007","journal-title":"BMC Bioinf"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/S00894\u2013014-2278\u20135\/TABLES\/3","article-title":"AllerTOP v.2 - A server for in silico prediction of allergens","volume":"20","author":"Dimitrov","year":"2014","journal-title":"J Mol Model"},{"key":"B28","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1006\/cbir.1999.0355","article-title":"Protein identification and analysis tools in the ExPASy server","volume":"23","author":"Cash","year":"1999","journal-title":"Cell Biol Int"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1006","article-title":"The immune epitope database (IEDB): 2018 update","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s10989-020-10076-w","article-title":"Delineating novel therapeutic drug and vaccine targets for staphylococcus cornubiensis NW1T through computational analysis","volume":"27","author":"Shah","year":"2021","journal-title":"Int J Pept Res Ther"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: Improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"Reynisson","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1745-6150-8-30","article-title":"Designing of interferon-gamma inducing MHC class-II binders","volume":"8","author":"Dhanda","year":"2013","journal-title":"Biol Direct"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10091476","article-title":"mRNA vaccine designing using chikungunya virus E glycoprotein through immunoinformatics-guided approaches","volume":"10","author":"Jaan","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.7150\/jca.65074","article-title":"Combinations of radiotherapy with immunotherapy in cervical cancer","volume":"2022","author":"Yang","year":"2022","journal-title":"J Cancer"},{"key":"B35","doi-asserted-by":"publisher","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":"Jaan","year":"2022","journal-title":"Front Microbiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq551","article-title":"High-throughput prediction of protein antigenicity using protein microarray data","volume":"26","author":"Magnan","year":"2010","journal-title":"Bioinformatics"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/S00894\u2013001-0058\u20135","article-title":"New quantitative descriptors of amino acids based on multidimensional scaling of a large number of physical-chemical properties","volume":"7","author":"Venkatarajan","year":"2001","journal-title":"J Mol Model"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx345","article-title":"Protein-Sol: A web tool for predicting protein solubility from sequence","volume":"33","author":"Hebditch","year":"2017","journal-title":"Bioinformatics"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4315","article-title":"Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes","volume":"305","author":"Krogh","year":"2001","journal-title":"J Mol Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-153","article-title":"Predicting population coverage of T-cell epitope-based diagnostics and vaccines","volume":"7","author":"Bui","year":"2006","journal-title":"BMC Bioinf"},{"key":"B41","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.meegid.2017.10.022","article-title":"Overlapping CD8 + and CD4 + T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach","volume":"56","author":"Adhikari","year":"2017","journal-title":"Infection Genet Evol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111952","article-title":"Decrypting the multi-genome data for chimeric vaccine designing against the antibiotic resistant Yersinia pestis","volume":"132","author":"Sarfraz","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/16.4.404","article-title":"The PSIPRED protein structure prediction server","volume":"16","author":"McGuffin","year":"2000","journal-title":"Bioinformatics"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt458","article-title":"GalaxyRefine: Protein structure refinement driven by side-chain repacking","volume":"41","author":"Heo","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg565","article-title":"VADAR: A web server for quantitative evaluation of protein structure quality","volume":"31","author":"Willard","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: a program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J Appl Crystallogr"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-9-514","article-title":"ElliPro: A new structure-based tool for the prediction of antibody epitopes","volume":"9","author":"Ponomarenko","year":"2008","journal-title":"BMC Bioinf"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein-protein docking","volume":"12","author":"Kozakov","year":"2017","journal-title":"Nat Protoc"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr497","article-title":"iMod: Multipurpose normal mode analysis in internal coordinates","volume":"27","author":"Lop\u00e9z-Blanco","year":"2011","journal-title":"Bioinformatics"},{"key":"B51","doi-asserted-by":"crossref","DOI":"10.1109\/SC.2006.54","article-title":"\u201cScalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters,\u201c","author":"Bowers","year":"2006"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2019.06.004","article-title":"Bringing molecular dynamics simulation data into view","volume":"44","author":"Hildebrand","year":"2019","journal-title":"Trends Biochem Sci"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Madhavi Sastry","year":"2013","journal-title":"J Comput Aided Mol Des"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1021\/ct900587b","article-title":"Prediction of absolute solvation free energies using molecular dynamics free energy perturbation and the OPLS force field","volume":"6","author":"Shivakumar","year":"2010","journal-title":"J Chem Theory Comput"},{"key":"B55","doi-asserted-by":"publisher","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":"Grote","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr335","article-title":"Immune system simulation online","volume":"27","author":"Rapin","year":"2011","journal-title":"Bioinformatics"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c07866","article-title":"Deciphering the immunogenicity of monkeypox proteins for designing the potential mRNA vaccine","volume":"8","author":"Shah","year":"2023","journal-title":"ACS Omega"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00228-X","article-title":"Antibody-mediated regulation of cellular immunity and the inflammatory response","volume":"24","author":"Casadevall","year":"2003","journal-title":"Trends Immunol"},{"key":"B59","doi-asserted-by":"publisher","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":"Qasim","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B60","doi-asserted-by":"publisher","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":"Aslam","year":"2021","journal-title":"Comput Biol Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering10040430","article-title":"Annotation of Potential Vaccine Targets and Designing of mRNA-Based Multi-Epitope Vaccine against Lumpy Skin Disease Virus via Reverse Vaccinology and Agent-Based Modeling","volume":"10","author":"Kakakhel","year":"2023","journal-title":"Bioengineering"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040201","article-title":"Liver fluke induces cholangiocarcinoma","volume":"4","author":"Sripa","year":"2007","journal-title":"PLoS Med"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004293","article-title":"A comprehensive public health conceptual framework and strategy to effectively combat cholangiocarcinoma in Thailand","volume":"10","author":"Khuntikeo","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e3282fbf9b3","article-title":"Cholangiocarcinoma: lessons from Thailand","volume":"24","author":"Sripa","year":"2008","journal-title":"Curr Opin Gastroenterol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2016.17.2.857","article-title":"Reinfection by opisthorchis viverrini after treatment with praziquantel","volume":"17","author":"Saengsawang","year":"2016","journal-title":"Asian Pac J Cancer Prev"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2022.105592","article-title":"Characterization of proteome wide antigenic epitopes to design proteins specific and proteome-wide ensemble vaccines against heartland virus using structural vaccinology and immune simulation approaches","volume":"168","author":"Suleman","year":"2022","journal-title":"Microb Pathog"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2164-8-189","article-title":"Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini","volume":"8","author":"Laha","year":"2007","journal-title":"BMC Genomics"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407617200","article-title":"AIP1\/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2-induced ASK1-JNK activation","volume":"279","author":"Zhang","year":"2004","journal-title":"J Biol Chem"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798322003928","article-title":"Racemic crystal structures of A-DNA duplexes","volume":"78","author":"Mandal","year":"2022","journal-title":"Acta Crystallogr D Struct Biol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.2010.12.issue-6","article-title":"Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini : regulation of cathepsin F activation by autocatalysis and trans- processing by cathepsin B","volume":"12","author":"Sripa","year":"2010","journal-title":"Cellular Microbiology"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000398","article-title":"Cathepsin F cysteine protease of the human liver fluke, opisthorchis viverrini","volume":"3","author":"Pinlaor","year":"2009","journal-title":"PLoS Negl Trop Dis"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2019.10.009","article-title":"Potential druggable proteins and chimeric vaccine construct prioritization against Brucella melitensis from species core genome data","volume":"112","author":"Aslam","year":"2020","journal-title":"Genomics"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1042997","article-title":"Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation","volume":"13","author":"Suleman","year":"2022","journal-title":"Front Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2020.03.006","article-title":"Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches","volume":"25","author":"Parvizpour","year":"2020","journal-title":"Drug Discovery Today"},{"key":"B75","doi-asserted-by":"publisher","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":"Khan","year":"2021","journal-title":"Comput Biol Med"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c04817","article-title":"Designing of a multi-epitope vaccine against the structural proteins of marburg virus exploiting the immunoinformatics approach","volume":"6","author":"Sami","year":"2021","journal-title":"ACS Omega"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11010061","article-title":"An immunoinformatics approach to design a potent multi-epitope vaccine against asia-1 genotype of crimean\u2013congo haemorrhagic fever virus using the structural glycoproteins as a target","volume":"11","author":"Shah","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B78","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41598-021-03990-6","article-title":"In silico construction of a multiepitope Zika virus vaccine using immunoinformatics tools","volume":"12","author":"Antonelli","year":"2022","journal-title":"Sci Rep"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.12.4491","article-title":"Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor","volume":"92","author":"Armitage","year":"1998","journal-title":"Blood"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.6185","article-title":"Application of built-in adjuvants for epitope-based vaccines","volume":"6","author":"Lei","year":"2019","journal-title":"PeerJ"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-01770-w","article-title":"Immunoprotective effect of an in silico designed multiepitope cancer vaccine with BORIS cancer - testis antigen target in a murine mammary carcinoma model","volume":"11","author":"Mahdevar","year":"2021","journal-title":"Sci Rep"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1186\/1745-7580-6-6","article-title":"Identification of conformational B-cell Epitopes in an antigen from its primary sequence","volume":"6","author":"Ansari","year":"2010","journal-title":"Immunome Res"},{"key":"B83","doi-asserted-by":"publisher","first-page":"297","DOI":"10.3390\/cancers12020297","article-title":"Toll-like receptors from the perspective of cancer treatment","volume":"12","author":"Javaid","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2005.02.003","article-title":"Opisthorchis viverrini antigen induces the expression of Toll-like receptor 2 in macrophage RAW cell line","volume":"35","author":"Pinlaor","year":"2005","journal-title":"International Journal for Parasitology"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2010.09.008","article-title":"Parasitology International Opisthorchis viverrini excretory \/ secretory products induce toll-like receptor 4 upregulation and production of interleukin 6 and 8 in cholangiocyte","volume":"59","author":"Ninlawan","year":"2010","journal-title":"Parasitol Int"}],"updated-by":[{"DOI":"10.3389\/fimmu.2025.1638914","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1281544\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T07:47:09Z","timestamp":1751269629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1281544\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,10]]},"references-count":85,"alternative-id":["10.3389\/fimmu.2024.1281544"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1281544","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fimmu.2025.1638914","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,10]]},"article-number":"1281544"}}