{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T14:57:11Z","timestamp":1793458631674,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["32070662"],"award-info":[{"award-number":["32070662"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Vaccines"],"abstract":"<jats:p>Tick-borne encephalitis virus (TBEV), belonging to the Flaviviridae family, is transmitted to humans via infected tick bites, leading to serious neurological complications and, in some cases, death. The available vaccines against the TBEV are reported to have low immunogenicity and are associated with adverse effects like swelling, redness and fever. Moreover, these vaccines are whole-organism-based, carry a risk of reactivation and potential for significant mortality. Consequently, to design a potential antigenic and non-allergenic multi-epitope subunit vaccine against the TBEV, we used an immunoinformatic approach to screen the Tick-borne virus proteome for highly antigenic CTL, HTL and B cell epitopes. The proper folding of the constructed vaccine was validated by a molecular dynamic simulation. Additionally, the molecular docking and binding free energy (\u221287.50 kcal\/mol) further confirmed the strong binding affinity of the constructed vaccine with TLR-4. The vaccine exhibited a CAI value of 0.93 and a GC content of 49%, showing a high expression capability in E coli. Moreover, the analysis of immune simulation demonstrated robust immune responses against the injected vaccine and clearance of the antigen with time. In conclusion, our vaccine candidate shows promise for both in vitro and in vivo analyses due to its high immunogenicity, non-allergenicity and stable interaction with the human TLR-4 receptor.<\/jats:p>","DOI":"10.3390\/vaccines9111210","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T22:07:04Z","timestamp":1634767624000},"page":"1210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Immunoinformatics and Immunogenetics-Based Design of Immunogenic Peptides Vaccine against the Emerging Tick-Borne Encephalitis Virus (TBEV) and Its Validation through In Silico Cloning and Immune Simulation"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-1862","authenticated-orcid":false,"given":"Muhammad","family":"Suleman","sequence":"first","affiliation":[{"name":"Centre for Biotechnology and Microbiology, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-4250","authenticated-orcid":false,"given":"Muhammad","family":"ul Qamar","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Kiran","sequence":"additional","affiliation":[{"name":"Department of Plant Breeding and Genetics, University of Agriculture, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samreen","family":"Rasool","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Government College University, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneela","family":"Rasool","sequence":"additional","affiliation":[{"name":"Department of Botany, University of Okara, Okara 56300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-5340","authenticated-orcid":false,"given":"Aqel","family":"Albutti","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-9921","authenticated-orcid":false,"given":"Noorah","family":"Alsowayeh","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Education, Majmaah University, Al Majma\u2019ah 15341, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7290-8945","authenticated-orcid":false,"given":"Ameen","family":"Alwashmi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3708-9200","authenticated-orcid":false,"given":"Mohammad","family":"Aljasir","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Health and Biological Sciences, Abasyn University, Peshawar 25120, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahid","family":"Hussain","sequence":"additional","affiliation":[{"name":"Centre for Biotechnology and Microbiology, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Rizwan","sequence":"additional","affiliation":[{"name":"Centre for Biotechnology and Microbiology, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Ali","sequence":"additional","affiliation":[{"name":"Centre for Biotechnology and Microbiology, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4200-7502","authenticated-orcid":false,"given":"Dong-Qing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China"},{"name":"Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1099\/vir.0.011437-0","article-title":"Tick-borne encephalitis virus\u2014A review of an emerging zoonosis","volume":"90","author":"Mansfield","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S0140-6736(08)60238-X","article-title":"Pathogenic flaviviruses","volume":"371","author":"Gould","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/S0140-6736(08)60800-4","article-title":"Tick-borne encephalitis","volume":"371","author":"Lindquist","year":"2008","journal-title":"Lancet"},{"key":"ref_4","first-page":"717","article-title":"Tick-borne encephalitis in europe and beyond\u2014The epidemiological situation as of 2007","volume":"13","year":"2008","journal-title":"Eurosurveillance"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"430","DOI":"10.12998\/wjcc.v3.i5.430","article-title":"Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management","volume":"3","author":"Bogovic","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1111\/ene.13356","article-title":"Ean consensus review on prevention, diagnosis and management of tick-borne encephalitis","volume":"24","author":"Taba","year":"2017","journal-title":"Eur. J. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8663","DOI":"10.1128\/JVI.01013-12","article-title":"Revisiting the clinal concept of evolution and dispersal for the tick-borne flaviviruses by using phylogenetic and biogeographic analyses","volume":"86","author":"Heinze","year":"2012","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1089\/vbz.2009.0020","article-title":"Integration of a tick-borne encephalitis virus and borrelia burgdorferi sensu lato into mountain ecosystems, following a shift in the altitudinal limit of distribution of their vector, ixodes ricinus (krkono\u0161e mountains, Czech republic)","volume":"10","author":"Daniel","year":"2010","journal-title":"Vector-Borne Zoonotic Dis."},{"key":"ref_9","first-page":"74","article-title":"Threshold of viraemia in apodemus flavicollis for infection of ixodes ricinus with tick-borne encephalitis virus","volume":"13","author":"Radda","year":"1969","journal-title":"Acta Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kubinski, M., Beicht, J., Gerlach, T., Volz, A., Sutter, G., and Rimmelzwaan, G.F. (2020). Tick-borne encephalitis virus: A quest for better vaccines against a virus on the rise. Vaccines, 8.","DOI":"10.3390\/vaccines8030451"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1093\/nar\/25.6.1194","article-title":"Secondary structure of the 3\u2032 untranslated region of flaviviruses: Similarities and differences","volume":"25","author":"Proutski","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.meegid.2017.09.014","article-title":"Reconsidering the classification of tick-borne encephalitis virus within the siberian subtype gives new insights into its evolutionary history","volume":"55","author":"Kovalev","year":"2017","journal-title":"Infect. Genet. Evol."},{"key":"ref_13","first-page":"1","article-title":"A new subtype of eastern tick-borne encephalitis virus discovered in qinghai-tibet plateau, china","volume":"7","author":"Dai","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1089\/vbz.2008.0028","article-title":"Tick-borne encephalitis in mainland china","volume":"8","author":"Lu","year":"2008","journal-title":"Vector-Borne Zoonotic Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1586\/erv.12.86","article-title":"Vaccines and vaccination against tick-borne encephalitis","volume":"11","author":"Kollaritsch","year":"2012","journal-title":"Expert Rev. Vaccines"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1016\/S0264-410X(02)00814-9","article-title":"History of tbe vaccines","volume":"21","author":"Barrett","year":"2003","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Khan, S., Ali, S.S., Zaheer, I., Saleem, S., Zaman, N., Iqbal, A., Suleman, M., Wadood, A., and Rehman, A.U. (2020). Proteome-wide mapping and reverse vaccinology-based b and t cell multi-epitope subunit vaccine designing for immune response reinforcement against porphyromonas gingivalis. J. Biomol. Struct. Dyn., 1\u201315.","DOI":"10.1080\/07391102.2020.1819423"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ahmad, I., Ali, S.S., Shah, I., Khan, S., Khan, M., Ullah, S., Ali, S., Khan, J., Ali, M., and Khan, A. (2020). Computational vaccinology based development of multi-epitope subunit vaccine for protection against the norovirus infections. bioRxiv.","DOI":"10.1101\/2020.03.18.997197"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104551","DOI":"10.1016\/j.meegid.2020.104551","article-title":"Subtractive proteomics and immunoinformatics approaches to explore bartonella bacilliformis proteome (virulence factors) to design b and t cell multi-epitope subunit vaccine","volume":"85","author":"Gul","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.meegid.2019.06.006","article-title":"Immunoinformatics and structural vaccinology driven prediction of multi-epitope vaccine against mayaro virus and validation through in-silico expression","volume":"73","author":"Khan","year":"2019","journal-title":"Infect. Genet. Evol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/s41598-018-37070-z","article-title":"Immunoinformatic and systems biology approaches to predict and validate peptide vaccines against epstein\u2013barr virus (ebv)","volume":"9","author":"Ali","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejps.2017.11.014","article-title":"Identification and characterization of potential druggable targets among hypothetical proteins of extensively drug resistant mycobacterium tuberculosis (xdr kzn 605) through subtractive genomics approach","volume":"114","author":"Uddin","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1002\/1521-4141(200006)30:6<1724::AID-IMMU1724>3.0.CO;2-A","article-title":"Efficient protection against mycobacterium tuberculosis by vaccination with a single subdominant epitope from the esat-6 antigen","volume":"30","author":"Hansen","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104389","DOI":"10.1016\/j.compbiomed.2021.104389","article-title":"Designing multi-epitope vaccine against staphylococcus aureus by employing subtractive proteomics, reverse vaccinology and immuno-informatics approaches","volume":"132","author":"Ahmad","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kathwate, G.H. (2020). In silico design and characterization of multiepitopes vaccine for SARS-CoV2 from its spike proteins. bioRxiv.","DOI":"10.1101\/2020.06.03.131755"},{"key":"ref_26","first-page":"1","article-title":"Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2","volume":"9","author":"Shahid","year":"2020","journal-title":"Infect. Dis. Poverty"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1142\/S0219720007002564","article-title":"Metabolic pathway analysis of s. Pneumoniae: An in silico approach towards drug-design","volume":"5","author":"Singh","year":"2007","journal-title":"J. Bioinform. Comput. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkn201","article-title":"Ncbi blast: A better web interface","volume":"36","author":"Johnson","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Larsen, M.V., Lundegaard, C., Lamberth, K., Buus, S., Lund, O., and Nielsen, M. (2007). Large-scale validation of methods for cytotoxic t-lymphocyte epitope prediction. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-424"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ponomarenko, J., Bui, H.-H., Li, W., Fusseder, N., Bourne, P.E., Sette, A., and Peters, B. (2008). Ellipro: A new structure-based tool for the prediction of antibody epitopes. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-514"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Saha, S., and Raghava, G.P. (2007). Prediction methods for b-cell epitopes. Immunoinformatics, Springer.","DOI":"10.1007\/978-1-60327-118-9_29"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/yea.1431","article-title":"A flexible protein linker improves the function of epitope-tagged proteins in saccharomyces cerevisiae","volume":"24","author":"Sabourin","year":"2007","journal-title":"Yeast"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lee, S.J., Shin, S.J., Lee, M.H., Lee, M.-G., Kang, T.H., Park, W.S., Soh, B.Y., Park, J.H., Shin, Y.K., and Kim, H.W. (2014). A potential protein adjuvant derived from mycobacterium tuberculosis rv0652 enhances dendritic cells-based tumor immunotherapy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104351"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W202","DOI":"10.1093\/nar\/gkl343","article-title":"Algpred: Prediction of allergenic proteins and mapping of ige epitopes","volume":"34","author":"Saha","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"398","DOI":"10.2174\/1573409915666190318121838","article-title":"Vaxijen dataset of bacterial immunogens: An update","volume":"15","author":"Zaharieva","year":"2019","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_36","first-page":"531","article-title":"Protein identification and analysis tools in the expasy server","volume":"112","author":"Wilkins","year":"1999","journal-title":"Methods Mol. Biol."},{"key":"ref_37","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":"McGuffin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/prot.23175","article-title":"Raptorx: Exploiting structure information for protein alignment by statistical inference","volume":"79","author":"Peng","year":"2011","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1101\/gr.4086505","article-title":"Galaxy: A platform for interactive large-scale genome analysis","volume":"15","author":"Giardine","year":"2005","journal-title":"Genome Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W407","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":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_41","first-page":"75","article-title":"Limitations of structure evaluation tools errat","volume":"16","author":"Lengths","year":"2018","journal-title":"Quick Guidel. Comput. Drug Des."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.1080\/07391102.2020.1772109","article-title":"Targeting the protein-protein interface pocket of aurora-a-tpx2 complex: Rational drug design and validation","volume":"39","author":"Bhardwaj","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/wcms.1121","article-title":"An overview of the amber biomolecular simulation package","volume":"3","author":"Case","year":"2013","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1021\/ct400314y","article-title":"Routine microsecond molecular dynamics simulations with amber on gpus. 2. Explicit solvent particle mesh ewald","volume":"9","author":"Gotz","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"Ptraj and cpptraj: Software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W363","DOI":"10.1093\/nar\/gki481","article-title":"Patchdock and symmdock: Servers for rigid and symmetric docking","volume":"33","author":"Inbar","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/prot.21495","article-title":"Firedock: Fast interaction refinement in molecular docking","volume":"69","author":"Andrusier","year":"2007","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the performance of the mm\/pbsa and mm\/gbsa methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations","volume":"51","author":"Hou","year":"2011","journal-title":"J. Chem. Inf. Modeling"},{"key":"ref_49","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":"Grote","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_50","unstructured":"G Biotech Snapgene viewer, Glick B, editor 3."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rapin, N., Lund, O., Bernaschi, M., and Castiglione, F. (2010). Computational immunology meets bioinformatics: The use of prediction tools for molecular binding in the simulation of the immune system. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009862"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.neuron.2018.08.011","article-title":"Molecular dynamics simulation for all","volume":"99","author":"Hollingsworth","year":"2018","journal-title":"Neuron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmolb.2021.692835","article-title":"Mutational landscape of pirin and elucidation of the impact of most detrimental missense variants that accelerate the breast cancer pathways: A computational modelling study","volume":"8","author":"Suleman","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13276","DOI":"10.1073\/pnas.1811364115","article-title":"Experimental accuracy in protein structure refinement via molecular dynamics simulations","volume":"115","author":"Heo","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4659","DOI":"10.1080\/07391102.2020.1779128","article-title":"Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3clpro)","volume":"39","author":"Khan","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41435-020-00120-6","article-title":"Evolutionary and structural analysis of SARS-CoV-2 specific evasion of host immunity","volume":"21","author":"Hussain","year":"2020","journal-title":"Genes Immun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7045","DOI":"10.1002\/jcp.30367","article-title":"Higher infectivity of the SARS-CoV-2 new variants is associated with k417n\/t, e484k, and n501y mutants: An insight from structural data","volume":"236","author":"Khan","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Khan, A., Heng, W., Wang, Y., Qiu, J., Wei, X., Peng, S., Saleem, S., Khan, M., Ali, S.S., and Wei, D.-Q. (2021). In silico and in vitro evaluation of kaempferol as a potential inhibitor of the SARS-CoV-2 main protease (3clpro). Phytother. Res., 1\u20133.","DOI":"10.1002\/ptr.6998"},{"key":"ref_59","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":"Khan","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/01.shk.0000180074.69143.77","article-title":"Implication of toll-like receptor and tumor necrosis factor alpha signaling in septic shock","volume":"24","author":"Lin","year":"2005","journal-title":"Shock"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.3201\/eid1811.120675","article-title":"Bartonella spp. Bacteremia and rheumatic symptoms in patients from lyme disease\u2013endemic region","volume":"18","author":"Beard","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S382","DOI":"10.1093\/infdis\/jix172","article-title":"The unique microbiology and molecular pathogenesis of mycoplasma genitalium","volume":"216","author":"McGowin","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Khan, A., Junaid, M., Kaushik, A.C., Ali, A., Ali, S.S., Mehmood, A., and Wei, D.-Q. (2018). Computational identification, characterization and validation of potential antigenic peptide vaccines from hrhpvs e6 proteins using immunoinformatics and computational systems biology approaches. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196484"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1586\/erv.09.160","article-title":"Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists","volume":"9","author":"Black","year":"2010","journal-title":"Expert Rev. Vaccines"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3390\/vaccines2030515","article-title":"Peptide vaccine: Progress and challenges","volume":"2","author":"Li","year":"2014","journal-title":"Vaccines"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/bs.apcsb.2015.03.002","article-title":"The use of liposomes to shape epitope structure and modulate immunogenic responses of peptide vaccines against hiv mper","volume":"Volume 99","author":"Nieva","year":"2015","journal-title":"Advances in Protein Chemistry and Structural Biology"},{"key":"ref_67","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":"Khan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8285","DOI":"10.1038\/s41598-017-08842-w","article-title":"Exploring leishmania secretory proteins to design b and t cell multi-epitope subunit vaccine using immunoinformatics approach","volume":"7","author":"Khatoon","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5915","DOI":"10.4049\/jimmunol.1500157","article-title":"A synthetic m protein peptide synergizes with a cxc chemokine protease to induce vaccine-mediated protection against virulent streptococcal pyoderma and bacteremia","volume":"194","author":"Pandey","year":"2015","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.biologicals.2017.08.004","article-title":"Towards a peptide-based vaccine against shigella sonnei: A subtractive reverse vaccinology based approach","volume":"50","author":"Baseer","year":"2017","journal-title":"Biologicals"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"492","DOI":"10.3399\/bjgp16X687013","article-title":"Prevention of tick-borne diseases: An overview","volume":"66","author":"Rahlenbeck","year":"2016","journal-title":"Br. J. Gen. Pract."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s12539-020-00381-9","article-title":"Phylogenetic analysis and structural perspectives of rna-dependent rna-polymerase inhibition from SARS-CoV-2 with natural products","volume":"12","author":"Khan","year":"2020","journal-title":"Interdiscip. Sci. Comput. Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1016\/j.csbj.2020.08.006","article-title":"Structural insights into the mechanism of rna recognition by the n-terminal rna-binding domain of the SARS-CoV-2 nucleocapsid phosphoprotein","volume":"18","author":"Khan","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."}],"updated-by":[{"DOI":"10.3390\/vaccines12080920","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000}}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/11\/1210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T22:42:07Z","timestamp":1754260927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/11\/1210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":73,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["vaccines9111210"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9111210","relation":{"correction":[{"id-type":"doi","id":"10.3390\/vaccines12080920","asserted-by":"object"}]},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]}}}