Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against <i>Yersinia pestis</i> through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach
Azaz Ul Haq,
Abbas Khan,
Jafar Khan,
Shamaila Irum,
Yasir Waheed,
Sajjad Ahmad,
N. Nizam-Uddin,
Aqel Albutti,
Nasib Zaman,
Zahid Hussain,
Syed Shujait Ali,
Muhammad Waseem,
Fariha Kanwal,
Dong-Qing Wei,
Qian Wang
Affiliations
Azaz Ul Haq
Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan
Abbas Khan
Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Jafar Khan
Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan
Shamaila Irum
Department of Zoology, University of Gujrat, Punjab 50700, Pakistan
Yasir Waheed
Multidisciplinary Department, Foundation University Medical College, Foundation University Islamabad, Islamabad 44000, Pakistan
Sajjad Ahmad
Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan
Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
Nasib Zaman
Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan
Zahid Hussain
Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan
Syed Shujait Ali
Center for Biotechnology and Microbiology, Kanju Campus, University of Swat, Swat 19200, Pakistan
Muhammad Waseem
Faculty of Rehabilitation and Allied Health Science, Riphah International University, Islamabad 46000, Pakistan
Fariha Kanwal
Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai 200240, China
Dong-Qing Wei
Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Qian Wang
Department of Medicine, Nanjing Medical University, No. 140, Hanzhong Road, Nanjing 210029, China
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–TLR 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.
