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Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei

The emergence of antibiotic resistance in bacterial species is a major threat to public health and has resulted in high mortality as well as high health care costs. Burkholderia mallei is one of the etiological agents of health care-associated infections. As no licensed vaccine is available against...

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Autores principales: Irfan, Muhammad, Khan, Saifullah, Hameed, Alaa R., Al-Harbi, Alhanouf I., Abideen, Syed Ainul, Ismail, Saba, Ullah, Asad, Abbasi, Sumra Wajid, Ahmad, Sajjad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607922/
https://www.ncbi.nlm.nih.gov/pubmed/36298444
http://dx.doi.org/10.3390/vaccines10101580
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author Irfan, Muhammad
Khan, Saifullah
Hameed, Alaa R.
Al-Harbi, Alhanouf I.
Abideen, Syed Ainul
Ismail, Saba
Ullah, Asad
Abbasi, Sumra Wajid
Ahmad, Sajjad
author_facet Irfan, Muhammad
Khan, Saifullah
Hameed, Alaa R.
Al-Harbi, Alhanouf I.
Abideen, Syed Ainul
Ismail, Saba
Ullah, Asad
Abbasi, Sumra Wajid
Ahmad, Sajjad
author_sort Irfan, Muhammad
collection PubMed
description The emergence of antibiotic resistance in bacterial species is a major threat to public health and has resulted in high mortality as well as high health care costs. Burkholderia mallei is one of the etiological agents of health care-associated infections. As no licensed vaccine is available against the pathogen herein, using reverse vaccinology, bioinformatics, and immunoinformatics approaches, a multi-epitope-based vaccine against B. mallei was designed. In completely sequenced proteomes of B. mallei, 18,405 core, 3671 non-redundant, and 14,734 redundant proteins were predicted. Among the 3671 non-redundant proteins, 3 proteins were predicted in the extracellular matrix, 11 were predicted as outer membrane proteins, and 11 proteins were predicted in the periplasmic membrane. Only two proteins, type VI secretion system tube protein (Hcp) and type IV pilus secretin proteins, were selected for epitope prediction. Six epitopes, EAMPERMPAA, RSSPPAAGA, DNRPISINL, RQRFDAHAR, AERERQRFDA, and HARAAQLEPL, were shortlisted for multi-epitopes vaccine design. The predicted epitopes were linked to each other via a specific GPGPG linker and the epitopes peptide was then linked to an adjuvant molecule through an EAAAK linker to make the designed vaccine more immunologically potent. The designed vaccine was also found to have favorable physicochemical properties with a low molecular weight and fewer transmembrane helices. Molecular docking studies revealed vaccine construct stable binding with MHC-I, MHC-II, and TLR-4 with energy scores of −944.1 kcal/mol, −975.5 kcal/mol, and −1067.3 kcal/mol, respectively. Molecular dynamic simulation assay noticed stable dynamics of the docked vaccine-receptors complexes and no drastic changes were observed. Binding free energies estimation revealed a net value of −283.74 kcal/mol for the vaccine-MHC-I complex, −296.88 kcal/mol for the vaccine-MHC-II complex, and −586.38 kcal/mol for the vaccine-TLR-4 complex. These findings validate that the designed vaccine construct showed promising ability in terms of binding to immune receptors and may be capable of eliciting strong immune responses once administered to the host. Further evidence from experimentations in mice models is required to validate real immune protection of the designed vaccine construct against B. mallei.
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spelling pubmed-96079222022-10-28 Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei Irfan, Muhammad Khan, Saifullah Hameed, Alaa R. Al-Harbi, Alhanouf I. Abideen, Syed Ainul Ismail, Saba Ullah, Asad Abbasi, Sumra Wajid Ahmad, Sajjad Vaccines (Basel) Article The emergence of antibiotic resistance in bacterial species is a major threat to public health and has resulted in high mortality as well as high health care costs. Burkholderia mallei is one of the etiological agents of health care-associated infections. As no licensed vaccine is available against the pathogen herein, using reverse vaccinology, bioinformatics, and immunoinformatics approaches, a multi-epitope-based vaccine against B. mallei was designed. In completely sequenced proteomes of B. mallei, 18,405 core, 3671 non-redundant, and 14,734 redundant proteins were predicted. Among the 3671 non-redundant proteins, 3 proteins were predicted in the extracellular matrix, 11 were predicted as outer membrane proteins, and 11 proteins were predicted in the periplasmic membrane. Only two proteins, type VI secretion system tube protein (Hcp) and type IV pilus secretin proteins, were selected for epitope prediction. Six epitopes, EAMPERMPAA, RSSPPAAGA, DNRPISINL, RQRFDAHAR, AERERQRFDA, and HARAAQLEPL, were shortlisted for multi-epitopes vaccine design. The predicted epitopes were linked to each other via a specific GPGPG linker and the epitopes peptide was then linked to an adjuvant molecule through an EAAAK linker to make the designed vaccine more immunologically potent. The designed vaccine was also found to have favorable physicochemical properties with a low molecular weight and fewer transmembrane helices. Molecular docking studies revealed vaccine construct stable binding with MHC-I, MHC-II, and TLR-4 with energy scores of −944.1 kcal/mol, −975.5 kcal/mol, and −1067.3 kcal/mol, respectively. Molecular dynamic simulation assay noticed stable dynamics of the docked vaccine-receptors complexes and no drastic changes were observed. Binding free energies estimation revealed a net value of −283.74 kcal/mol for the vaccine-MHC-I complex, −296.88 kcal/mol for the vaccine-MHC-II complex, and −586.38 kcal/mol for the vaccine-TLR-4 complex. These findings validate that the designed vaccine construct showed promising ability in terms of binding to immune receptors and may be capable of eliciting strong immune responses once administered to the host. Further evidence from experimentations in mice models is required to validate real immune protection of the designed vaccine construct against B. mallei. MDPI 2022-09-21 /pmc/articles/PMC9607922/ /pubmed/36298444 http://dx.doi.org/10.3390/vaccines10101580 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
Irfan, Muhammad
Khan, Saifullah
Hameed, Alaa R.
Al-Harbi, Alhanouf I.
Abideen, Syed Ainul
Ismail, Saba
Ullah, Asad
Abbasi, Sumra Wajid
Ahmad, Sajjad
Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei
title Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei
title_full Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei
title_fullStr Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei
title_full_unstemmed Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei
title_short Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei
title_sort computational based designing of a multi-epitopes vaccine against burkholderia mallei
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9607922/
https://www.ncbi.nlm.nih.gov/pubmed/36298444
http://dx.doi.org/10.3390/vaccines10101580
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