{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:00:35Z","timestamp":1780585235136,"version":"3.54.1"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"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":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Yersinia pestis is responsible for plague and major pandemics in Asia and Europe. This bacterium has shown resistance to an array of drugs commonly used for the treatment of plague. Therefore, effective therapeutics measurements, such as designing a vaccine that can effectively and safely prevent Y. pestis infection, are of high interest. To fast-track vaccine development against Yersinia pestis, herein, proteome-wide vaccine target annotation was performed, and structural vaccinology-assisted epitopes were predicted. Among the total 3909 proteins, only 5 (rstB, YPO2385, hmuR, flaA1a, and psaB) were shortlisted as essential vaccine targets. These targets were then subjected to multi-epitope vaccine design using different linkers. EAAK, AAY, and GPGPG as linkers were used to link CTL, HTL, and B-cell epitopes, and an adjuvant (beta defensin) was also added at the N-terminal of the MEVC. Physiochemical characterization, such as determination of the instability index, theoretical pI, half-life, aliphatic index, stability profiling, antigenicity, allergenicity, and hydropathy of the ensemble, showed that the vaccine is highly stable, antigenic, and non-allergenic and produces multiple interactions with immune receptors upon docking. In addition, molecular dynamics simulation confirmed the stable binding and good dynamic properties of the vaccine\u2013TLR complex. Furthermore, in silico and immune simulation of the developed MEVC for Y. pestis showed that the vaccine triggered strong immune response after several doses at different intervals. Neutralization of the antigen was observed at the third day of injection. Conclusively, the vaccine designed here for Y. pestis produces an immune response; however, further immunological testing is needed to unveil its real efficacy.<\/jats:p>","DOI":"10.3390\/vaccines9111327","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T20:46:47Z","timestamp":1637009207000},"page":"1327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach"],"prefix":"10.3390","volume":"9","author":[{"given":"Azaz Ul","family":"Haq","sequence":"first","affiliation":[{"name":"Center for Biotechnology and Microbiology, Kanju Campus, 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\/0000-0001-6361-9300","authenticated-orcid":false,"given":"Jafar","family":"Khan","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamaila","family":"Irum","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Gujrat, Punjab 50700, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5789-4215","authenticated-orcid":false,"given":"Yasir","family":"Waheed","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department, Foundation University Medical College, Foundation University Islamabad, Islamabad 44000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Nizam-Uddin","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, HITEC University, Taxila 47080, 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\/0000-0002-6960-6516","authenticated-orcid":false,"given":"Nasib","family":"Zaman","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahid","family":"Hussain","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Shujait","family":"Ali","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1927-3899","authenticated-orcid":false,"given":"Muhammad","family":"Waseem","sequence":"additional","affiliation":[{"name":"Faculty of Rehabilitation and Allied Health Science, Riphah International University, Islamabad 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariha","family":"Kanwal","sequence":"additional","affiliation":[{"name":"Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiaotong 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":"Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen 518055, 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Nanjing Medical University, No. 140, Hanzhong Road, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.tim.2015.11.008","article-title":"Pneumonic plague: The darker side of Yersinia pestis","volume":"24","author":"Pechous","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7620","DOI":"10.1073\/pnas.1901145116","article-title":"Plague, camels, and lice","volume":"116","author":"Barbieri","year":"2019","journal-title":"Proc. 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