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Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques

Whipple’s disease is caused by T. whipplei, a Gram-positive pathogenic bacterium. It is considered a persistent infection affecting various organs, more likely to infect males. There is currently no licensed vaccination available for Whipple’s disease; thus, the development of a chimeric peptide-bas...

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Autores principales: Albekairi, Thamer H., Alshammari, Abdulrahman, Alharbi, Metab, Alshammary, Amal F., Tahir ul Qamar, Muhammad, Anwar, Tasneem, Ismail, Saba, Shaker, Bilal, Ahmad, Sajjad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147804/
https://www.ncbi.nlm.nih.gov/pubmed/35632446
http://dx.doi.org/10.3390/vaccines10050691
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author Albekairi, Thamer H.
Alshammari, Abdulrahman
Alharbi, Metab
Alshammary, Amal F.
Tahir ul Qamar, Muhammad
Anwar, Tasneem
Ismail, Saba
Shaker, Bilal
Ahmad, Sajjad
author_facet Albekairi, Thamer H.
Alshammari, Abdulrahman
Alharbi, Metab
Alshammary, Amal F.
Tahir ul Qamar, Muhammad
Anwar, Tasneem
Ismail, Saba
Shaker, Bilal
Ahmad, Sajjad
author_sort Albekairi, Thamer H.
collection PubMed
description Whipple’s disease is caused by T. whipplei, a Gram-positive pathogenic bacterium. It is considered a persistent infection affecting various organs, more likely to infect males. There is currently no licensed vaccination available for Whipple’s disease; thus, the development of a chimeric peptide-based vaccine against T. whipplei has the potential to be tremendously beneficial in preventing Whipple’s disease in the future. The present study aimed to apply modern computational approaches to generate a multi-epitope-based vaccine that expresses antigenic determinants prioritized from the core proteome of two T. whipplei whole proteomes. Using an integrated computational approach, four immunodominant epitopes were found from two extracellular proteins. Combined, these epitopes covered 89.03% of the global population. The shortlisted epitopes exhibited a strong binding affinity for the B- and T-cell reference set of alleles, high antigenicity score, nonallergenic nature, high solubility, nontoxicity, and excellent binders of DRB1*0101. Through the use of appropriate linkers and adjuvation with a suitable adjuvant molecule, the epitopes were designed into a chimeric vaccine. An adjuvant was linked to the connected epitopes to boost immunogenicity and efficiently engage both innate and adaptive immunity. The physiochemical properties of the vaccine were observed favorable, leading toward the 3D modeling of the construct. Furthermore, the vaccine’s binding confirmation to the TLR-4 critical innate immune receptor was also determined using molecular docking and molecular dynamics (MD) simulations, which shows that the vaccine has a strong binding affinity for TLR4 (−29.4452 kcal/mol in MM-GBSA and −42.3229 kcal/mol in MM-PBSA). Overall, the vaccine described here has a promising potential for eliciting protective and targeted immunogenicity, subject to further experimental testing.
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spelling pubmed-91478042022-05-29 Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques Albekairi, Thamer H. Alshammari, Abdulrahman Alharbi, Metab Alshammary, Amal F. Tahir ul Qamar, Muhammad Anwar, Tasneem Ismail, Saba Shaker, Bilal Ahmad, Sajjad Vaccines (Basel) Article Whipple’s disease is caused by T. whipplei, a Gram-positive pathogenic bacterium. It is considered a persistent infection affecting various organs, more likely to infect males. There is currently no licensed vaccination available for Whipple’s disease; thus, the development of a chimeric peptide-based vaccine against T. whipplei has the potential to be tremendously beneficial in preventing Whipple’s disease in the future. The present study aimed to apply modern computational approaches to generate a multi-epitope-based vaccine that expresses antigenic determinants prioritized from the core proteome of two T. whipplei whole proteomes. Using an integrated computational approach, four immunodominant epitopes were found from two extracellular proteins. Combined, these epitopes covered 89.03% of the global population. The shortlisted epitopes exhibited a strong binding affinity for the B- and T-cell reference set of alleles, high antigenicity score, nonallergenic nature, high solubility, nontoxicity, and excellent binders of DRB1*0101. Through the use of appropriate linkers and adjuvation with a suitable adjuvant molecule, the epitopes were designed into a chimeric vaccine. An adjuvant was linked to the connected epitopes to boost immunogenicity and efficiently engage both innate and adaptive immunity. The physiochemical properties of the vaccine were observed favorable, leading toward the 3D modeling of the construct. Furthermore, the vaccine’s binding confirmation to the TLR-4 critical innate immune receptor was also determined using molecular docking and molecular dynamics (MD) simulations, which shows that the vaccine has a strong binding affinity for TLR4 (−29.4452 kcal/mol in MM-GBSA and −42.3229 kcal/mol in MM-PBSA). Overall, the vaccine described here has a promising potential for eliciting protective and targeted immunogenicity, subject to further experimental testing. MDPI 2022-04-28 /pmc/articles/PMC9147804/ /pubmed/35632446 http://dx.doi.org/10.3390/vaccines10050691 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Albekairi, Thamer H.
Alshammari, Abdulrahman
Alharbi, Metab
Alshammary, Amal F.
Tahir ul Qamar, Muhammad
Anwar, Tasneem
Ismail, Saba
Shaker, Bilal
Ahmad, Sajjad
Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques
title Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques
title_full Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques
title_fullStr Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques
title_full_unstemmed Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques
title_short Design of a Multi-Epitope Vaccine against Tropheryma whipplei Using Immunoinformatics and Molecular Dynamics Simulation Techniques
title_sort design of a multi-epitope vaccine against tropheryma whipplei using immunoinformatics and molecular dynamics simulation techniques
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147804/
https://www.ncbi.nlm.nih.gov/pubmed/35632446
http://dx.doi.org/10.3390/vaccines10050691
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