{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:05:16Z","timestamp":1788793516710,"version":"build-2803163510"},"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Human parechovirus (HPeV) is widely recognized as a severe viral infection affecting infants and neonates. Belonging to the <jats:italic>Picornaviridae<\/jats:italic> family, HPeV is categorized into 19 distinct genotypes. Among them, HPeV-1 is the most prevalent genotype, primarily associated with respiratory and digestive symptoms. Considering HPeV\u2019s role as a leading cause of life-threatening viral infections in infants and the lack of effective antiviral therapies, our focus centered on developing two multi-epitope vaccines, namely HPeV-Vax-1 and HPeV-Vax-2, using advanced immunoinformatic techniques. Multi-epitope vaccines have the advantage of protecting against various virus strains and may be preferable to live attenuated vaccines. Using the NCBI database, three viral protein sequences (VP0, VP1, and VP3) from six HPeV strains were collected to construct consensus protein sequences. Then the antigenicity, toxicity, allergenicity, and stability were analyzed after discovering T-cell and linear B-cell epitopes from the protein sequences. The fundamental structures of the vaccines were produced by fusing the selected epitopes with appropriate linkers and adjuvants. Comprehensive physicochemical, antigenic, allergic assays, and disulfide engineering demonstrated the effectiveness of the vaccines. Further refinement of secondary and tertiary models for both vaccines revealed promising interactions with toll-like receptor 4 (TLR4) in molecular docking, further confirmed by molecular dynamics simulation. <jats:italic>In silico<\/jats:italic> immunological modeling was employed to assess the vaccine\u2019s capacity to stimulate an immune reaction. <jats:italic>In silico<\/jats:italic> immunological simulations were employed to evaluate the vaccines\u2019 ability to trigger an immune response. Codon optimization and <jats:italic>in silico<\/jats:italic> cloning analyses showed that <jats:italic>Escherichia coli (E<\/jats:italic>. <jats:italic>coli)<\/jats:italic> was most likely the host for the candidate vaccines. Our findings suggest that these multi-epitope vaccines could be the potential HPeV vaccines and are recommended for further wet-lab investigation.<\/jats:p>","DOI":"10.1371\/journal.pone.0302120","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T18:34:07Z","timestamp":1733337247000},"page":"e0302120","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["In Silico design of a multi-epitope vaccine for Human Parechovirus: Integrating immunoinformatics and computational techniques"],"prefix":"10.1371","volume":"19","author":[{"given":"Arnob","family":"Sarker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Mahmudur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7584-5257","authenticated-orcid":true,"given":"Chadni","family":"Khatun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan","family":"Barai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayan","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Abdul","family":"Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1226-7226","authenticated-orcid":true,"given":"Md. 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Comas-Garcia","year":"2019","journal-title":"Viruses"},{"key":"pone.0302120.ref002","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1128\/mr.54.3.316-329.1990","article-title":"Parvovirus replication.","volume":"54","author":"KI Berns","year":"1990","journal-title":"Microbiol Rev"},{"key":"pone.0302120.ref003","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.idc.2015.05.005","article-title":"Human Parechovirus 3: The Most Common Viral Cause of Meningoencephalitis in Young Infants.","volume":"29","author":"C Renaud","year":"2015","journal-title":"Infect Dis Clin North Am."},{"key":"pone.0302120.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/CMR.00047-17","article-title":"Human Parechovirus: an Increasingly Recognized Cause of","volume":"31","author":"L Olijve","year":"2018","journal-title":"Clin Microbiol 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Palewar","year":"2022","journal-title":"J Fam Med Prim Care"},{"key":"pone.0302120.ref008","article-title":"Challenges and Recent Advancements in COVID-19 Vaccines.","volume":"11","author":"SC Wang","year":"2023","journal-title":"Microorganisms"},{"key":"pone.0302120.ref009","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.01181","article-title":"Current Challenges in Vaccinology.","volume":"11","author":"RB Kennedy","year":"2020","journal-title":"Front Immunol."},{"key":"pone.0302120.ref010","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.drudis.2020.03.006","article-title":"Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches","volume":"25","author":"S Parvizpour","year":"2020","journal-title":"Drug Discov Today"},{"key":"pone.0302120.ref011","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.112160","article-title":"Evaluation of humoral and cellular immune responses against Vibrio cholerae using oral immunization by multi-epitope-phage-based vaccine","volume":"134","author":"E Ghafouri","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"pone.0302120.ref012","article-title":"Self-Assembled Multiepitope Nanovaccine Provides Long-Lasting Cross-Protection against Influenza Virus.","volume":"13","author":"J Nie","year":"2024","journal-title":"Adv Healthc Mater."},{"key":"pone.0302120.ref013","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."},{"key":"pone.0302120.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0300507","article-title":"Multi-epitope vaccine design using in silico analysis of glycoprotein and nucleocapsid of NIPAH virus","volume":"19","author":"A Kumar","year":"2024","journal-title":"PLoS One"},{"key":"pone.0302120.ref015","article-title":"Design and evaluation of a multi-epitope DNA vaccine against HPV16.","volume":"20","author":"L Zhu","year":"2024","journal-title":"Hum Vaccines Immunother."},{"key":"pone.0302120.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0302390","article-title":"Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions.","volume":"19","author":"SC Ja\u2019afaru","year":"2024","journal-title":"PLoS One."},{"key":"pone.0302120.ref017","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/molbev\/msp259","article-title":"SeaView Version 4: A Multiplatform Graphical User Interface for Sequence Alignment and Phylogenetic Tree Building","volume":"27","author":"O Gascuel","year":"2010","journal-title":"Mol Biol Evol"},{"key":"pone.0302120.ref018","doi-asserted-by":"crossref","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"},{"key":"pone.0302120.ref019","volume-title":"Clinical Immunology: Principles and Practice Expert Consult: Online and Print","author":"SN Mueller","year":"2008","edition":"3"},{"key":"pone.0302120.ref020","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1186\/1471-2105-8-424","article-title":"Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction","volume":"8","author":"M V. Larsen","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"pone.0302120.ref021","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0073957","article-title":"In Silico Approach for Predicting Toxicity of Peptides and Proteins.","volume":"8","author":"S Gupta","year":"2013","journal-title":"PLoS One"},{"key":"pone.0302120.ref022","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-14-S6-S4","article-title":"AllerTOP\u2014a server for in silico prediction of allergens","volume":"14","author":"I Dimitrov","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"pone.0302120.ref023","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/BF02788751","article-title":"The optimization of helper T lymphocyte (HTL) function in vaccine development.","volume":"18","author":"J Alexander","year":"1998","journal-title":"Immunol Res"},{"key":"pone.0302120.ref024","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0952-7915(00)00103-5","article-title":"The role of CD4+ T helper cells in the cytotoxic T lymphocyte response to HIV-1","volume":"12","author":"M Altfeld","year":"2000","journal-title":"Curr Opin Immunol"},{"key":"pone.0302120.ref025","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/imm.12889","article-title":"Improved methods for predicting peptide binding affinity to MHC class II molecules","volume":"154","author":"KK Jensen","year":"2018","journal-title":"Immunology"},{"key":"pone.0302120.ref026","doi-asserted-by":"crossref","DOI":"10.1186\/1745-6150-8-30","article-title":"Designing of interferon-gamma inducing MHC class-II binders","volume":"8","author":"SK Dhanda","year":"2013","journal-title":"Biol Direct"},{"key":"pone.0302120.ref027","doi-asserted-by":"crossref","first-page":"263952","DOI":"10.1155\/2013\/263952","article-title":"Prediction of IL4 inducing peptides","volume":"2013","author":"SK Dhanda","year":"2013","journal-title":"Clin Dev Immunol"},{"key":"pone.0302120.ref028","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ni.3056","article-title":"Antiviral B cell and T cell immunity in the lungs","volume":"16","author":"C Chiu","year":"2015","journal-title":"Nat Immunol"},{"key":"pone.0302120.ref029","doi-asserted-by":"crossref","first-page":"W24","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"MC Jespersen","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"pone.0302120.ref030","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fgene.2023.866407","article-title":"An HLA map of the world: A comparison of HLA frequencies in 200 worldwide populations reveals diverse patterns for class I and class II.","volume":"14","author":"E Arrieta-Bola\u00f1os","year":"2023","journal-title":"Front Genet."},{"key":"pone.0302120.ref031","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":"S Southwood","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"pone.0302120.ref032","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41573-021-00163-y","article-title":"Emerging concepts in the science of vaccine adjuvants","volume":"20","author":"S. Pulendran B","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"pone.0302120.ref033","doi-asserted-by":"crossref","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"},{"key":"pone.0302120.ref034","article-title":"Immunoinformatics Design of Multi-Epitope Peptide-Based Vaccine Against Schistosoma mansoni Using Transmembrane Proteins as a Target.","volume":"12","author":"RCO Sanches","year":"2021","journal-title":"Front Immunol"},{"key":"pone.0302120.ref035","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.01784","article-title":"Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches.","volume":"11","author":"R Dong","year":"2020","journal-title":"Front Immunol."},{"key":"pone.0302120.ref036","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-99227-7","article-title":"Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus","volume":"11","author":"AO Fadaka","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0302120.ref037","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1016\/j.vaccine.2018.03.042","article-title":"Immunoinformatics approaches to design a novel multi-epitope subunit vaccine against HIV infection","volume":"36","author":"RK Pandey","year":"2018","journal-title":"Vaccine"},{"key":"pone.0302120.ref038","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1093\/bioinformatics\/btt619","article-title":"AllergenFP: Allergenicity prediction by descriptor fingerprints","volume":"30","author":"I Dimitrov","year":"2014","journal-title":"Bioinformatics"},{"key":"pone.0302120.ref039","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1093\/bioinformatics\/btx345","article-title":"Protein-Sol: A web tool for predicting protein solubility from sequence","volume":"33","author":"M Hebditch","year":"2017","journal-title":"Bioinformatics"},{"key":"pone.0302120.ref040","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"},{"key":"pone.0302120.ref041","author":"E. Gasteiger","year":"2014","journal-title":"ExPASy\u2014the proteomics server for in-depth protein knowledge and analysis"},{"key":"pone.0302120.ref042","first-page":"2022.04.08.487609","author":"J Hallgren","year":"2022"},{"key":"pone.0302120.ref043","doi-asserted-by":"crossref","first-page":"W510","DOI":"10.1093\/nar\/gkac439","article-title":"NetSurfP-3.0: accurate and fast prediction of protein structural features by protein language models and deep learning","volume":"50","author":"MH H\u00f8ie","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"pone.0302120.ref044","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: A unified platform for automated protein structure and function prediction.","volume":"5","author":"A Roy","year":"2010","journal-title":"Nat Protoc."},{"key":"pone.0302120.ref045","doi-asserted-by":"crossref","first-page":"W174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER server: New development for protein structure and function predictions","volume":"43","author":"J Yang","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"pone.0302120.ref046","article-title":"GalaxyRefine: Protein structure refinement driven by side-chain repacking","volume":"41","author":"L Heo","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"pone.0302120.ref047","article-title":"The structure assessment web server: for proteins, complexes and more","author":"AM Waterhouse","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"pone.0302120.ref048","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"M Wiederstein","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"pone.0302120.ref049","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1093\/bioinformatics\/btt473","article-title":"lDDT: a local superposition-free score for comparing protein structures and models using distance difference tests","volume":"29","author":"Valerio Mariani","year":"2013","journal-title":"Bioinformatics"},{"key":"pone.0302120.ref050","article-title":"In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases","volume":"9","author":"RA Shey","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0302120.ref051","doi-asserted-by":"crossref","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.0302120.ref052","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nprot.2016.169","article-title":"The ClusPro web server for protein-protein docking.","volume":"12","author":"D Kozakov","year":"2017","journal-title":"Nat Protoc."},{"key":"pone.0302120.ref053","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.str.2020.06.006","article-title":"Performance and Its Limits in Rigid Body Protein-Protein Docking","volume":"28","author":"IT Desta","year":"2020","journal-title":"Structure"},{"key":"pone.0302120.ref054","article-title":"Discovery Studio Life Science Modeling and Simulations.","author":"A. Corporate","year":"2008","journal-title":"ResearchgateNet1\u20138"},{"key":"pone.0302120.ref055","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1529\/biophysj.108.135814","article-title":"DARS (Decoys As the Reference State) potentials for protein-protein docking.","volume":"95","author":"GY Chuang","year":"2008","journal-title":"Biophys J"},{"key":"pone.0302120.ref056","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/pro.3289","article-title":"PDBsum: Structural summaries of PDB entries","volume":"27","author":"RA Laskowski","year":"2018","journal-title":"Protein Sci"},{"key":"pone.0302120.ref057","first-page":"82","article-title":"PyMOL The PyMOL Molecular Graphics System.","volume":"40","author":"L. Schr\u00f6dinger","year":"2010","journal-title":"CCP4 Newsl Protein Crystallogr."},{"key":"pone.0302120.ref058","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-14-346","article-title":"Disulfide by Design 2.0: A web-based tool for disulfide engineering in proteins","volume":"14","author":"DB Craig","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"pone.0302120.ref059","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/protein\/12.7.535","article-title":"Amino acid neighbours and detailed conformational analysis of cysteines in proteins","volume":"12","author":"MTN Petersen","year":"1999","journal-title":"Protein Eng"},{"key":"pone.0302120.ref060","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1093\/bioinformatics\/btu426","article-title":"YASARA View\u2014molecular graphics for all devices\u2014from smartphones to workstations | Bioinformatics | Oxford Academic","author":"E Krieger","year":"2014","journal-title":"Bioinformatics"},{"key":"pone.0302120.ref061","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1021\/ct4010307","article-title":"Lipid14: The amber lipid force field.","volume":"10","author":"CJ Dickson","year":"2014","journal-title":"J Chem Theory Comput"},{"key":"pone.0302120.ref062","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"WL Jorgensen","year":"1983","journal-title":"J Chem Phys"},{"key":"pone.0302120.ref063","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.jmgm.2006.02.009","article-title":"Fast empirical pKa prediction by Ewald summation","volume":"25","author":"E Krieger","year":"2006","journal-title":"J Mol Graph Model"},{"key":"pone.0302120.ref064","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/jcc.23899","article-title":"New ways to boost molecular dynamics simulations","volume":"36","author":"E Krieger","year":"2015","journal-title":"J Comput Chem"},{"key":"pone.0302120.ref065","first-page":"3586","article-title":"Molecular dynamics with coupling to an external bath","volume":"81","author":"LD Schuler","year":"2001","journal-title":"J Chem Phys"},{"key":"pone.0302120.ref066","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/prot.10104","article-title":"Increasing the precision of comparative models with YASARA NOVA\u2014A self-parameterizing force field","volume":"47","author":"E Krieger","year":"2002","journal-title":"Proteins Struct Funct Genet"},{"key":"pone.0302120.ref067","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0009862","article-title":"Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System.","volume":"5","author":"N Rapin","year":"2010","journal-title":"PLoS One"},{"key":"pone.0302120.ref068","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/842329","article-title":"How the interval between prime and boost injection affects the immune response in a computational model of the immune system.","volume":"2012","author":"F Castiglione","year":"2012","journal-title":"Comput Math Methods Med."},{"key":"pone.0302120.ref069","doi-asserted-by":"crossref","first-page":"W526","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 Res"},{"key":"pone.0302120.ref070","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0022-2836(82)90515-0","article-title":"A simple method for displaying the hydropathic character of a protein","volume":"157","author":"Jack Kyte","year":"1982","journal-title":"J Mol Biol"},{"key":"pone.0302120.ref071","article-title":"An in silico deep learning approach to multi-epitope vaccine design: a SARS-CoV-2 case study.","volume":"11","author":"Z Yang","year":"2021","journal-title":"Sci Rep."},{"key":"pone.0302120.ref072","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/JLB.4MIR0420-619RR","article-title":"Changing the paradigm of IFN-\u03b3 at the interface between innate and adaptive immunity: Macrophage-derived IFN-\u03b3","volume":"108","author":"S Mezouar","year":"2020","journal-title":"J Leukoc Biol"},{"key":"pone.0302120.ref073","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.meegid.2018.03.007","article-title":"Excavating chikungunya genome to design B and T cell multi-epitope subunit vaccine using comprehensive immunoinformatics approach to control chikungunya infection","volume":"61","author":"A Narula","year":"2018","journal-title":"Infect Genet Evol"},{"key":"pone.0302120.ref074","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2807\/1560-7917.ES2014.19.46.20964","article-title":"Presence of human non-polio enterovirus and parechovirus genotypes in an Amsterdam hospital in 2007 to 2011 compared to national and international published surveillance data: A comprehensive review.","volume":"19","author":"VA Janes","year":"2014","journal-title":"Eurosurveillance"},{"key":"pone.0302120.ref075","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/cmi.2017.92","article-title":"Multi-epitope vaccines: A promising strategy against tumors and viral infections","volume":"15","author":"L. Zhang","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"pone.0302120.ref076","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/CMR.00047-17","article-title":"Human parechovirus: An increasingly recognized cause of sepsis-like illness in young infants","volume":"31","author":"L Olijve","year":"2018","journal-title":"Clin Microbiol Rev"},{"key":"pone.0302120.ref077","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/B978-0-323-04404-2.10027-2","article-title":"Immune responses to viruses","author":"S. N. Mueller","year":"2008","journal-title":"In Clinical Immunology"},{"key":"pone.0302120.ref078","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":"2023","journal-title":"Curr Comput Aided Drug Des."},{"key":"pone.0302120.ref079","article-title":"An In Silico Multi-epitopes Vaccine Ensemble and Characterization Against Nosocomial Proteus penneri","author":"A Ullah","year":"2023","journal-title":"Mol Biotechnol"},{"key":"pone.0302120.ref080","doi-asserted-by":"crossref","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 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