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

<i>Yersinia pestis</i> 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 an...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Yersinia pestis</i> vaccine targets epitope mining in silico cloning immune simulation Medicine R
Acceso en línea:	https://doaj.org/article/df1d889ee75d4af986f027c372b202d5
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spelling	oai:doaj.org-article:df1d889ee75d4af986f027c372b202d52021-11-25T19:11:22ZAnnotation 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 Approach10.3390/vaccines91113272076-393Xhttps://doaj.org/article/df1d889ee75d4af986f027c372b202d52021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1327https://doaj.org/toc/2076-393X<i>Yersinia pestis</i> 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 <i>Y. pestis</i> infection, are of high interest. To fast-track vaccine development against <i>Yersinia pestis</i>, 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 <i>Y. pestis</i> 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 <i>Y. pestis</i> produces an immune response; however, further immunological testing is needed to unveil its real efficacy.Azaz Ul HaqAbbas KhanJafar KhanShamaila IrumYasir WaheedSajjad AhmadN. Nizam-UddinAqel AlbuttiNasib ZamanZahid HussainSyed Shujait AliMuhammad WaseemFariha KanwalDong-Qing WeiQian WangMDPI AGarticle<i>Yersinia pestis</i>vaccine targetsepitope miningin silico cloningimmune simulationMedicineRENVaccines, Vol 9, Iss 1327, p 1327 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Yersinia pestis</i> vaccine targets epitope mining in silico cloning immune simulation Medicine R
spellingShingle	<i>Yersinia pestis</i> vaccine targets epitope mining in silico cloning immune simulation Medicine R 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 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
description	<i>Yersinia pestis</i> 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 <i>Y. pestis</i> infection, are of high interest. To fast-track vaccine development against <i>Yersinia pestis</i>, 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 <i>Y. pestis</i> 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 <i>Y. pestis</i> produces an immune response; however, further immunological testing is needed to unveil its real efficacy.
format	article
author	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
author_facet	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
author_sort	Azaz Ul Haq
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/df1d889ee75d4af986f027c372b202d5
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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

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