Computational Based Designing of a Multi-Epitopes Vaccine against <i>Burkholderia mallei</i>
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. <i>Burkholderia mallei</i> is one of the etiological agents of health care-associated infections. As no licensed vaccine is...
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MDPI AG
2022-09-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/10/1580 |
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| author | Muhammad Irfan Saifullah Khan Alaa R. Hameed Alhanouf I. Al-Harbi Syed Ainul Abideen Saba Ismail Asad Ullah Sumra Wajid Abbasi Sajjad Ahmad |
| author_facet | Muhammad Irfan Saifullah Khan Alaa R. Hameed Alhanouf I. Al-Harbi Syed Ainul Abideen Saba Ismail Asad Ullah Sumra Wajid Abbasi Sajjad Ahmad |
| author_sort | Muhammad Irfan |
| collection | DOAJ |
| 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. <i>Burkholderia mallei</i> 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 <i>B. mallei</i> was designed. In completely sequenced proteomes of <i>B. mallei</i>, 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 <i>B. mallei</i>. |
| first_indexed | 2024-03-09T19:24:36Z |
| format | Article |
| id | doaj.art-19dfa00061074fa49d92812395a0acc9 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T19:24:36Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-19dfa00061074fa49d92812395a0acc92023-11-24T03:02:20ZengMDPI AGVaccines2076-393X2022-09-011010158010.3390/vaccines10101580Computational Based Designing of a Multi-Epitopes Vaccine against <i>Burkholderia mallei</i>Muhammad Irfan0Saifullah Khan1Alaa R. Hameed2Alhanouf I. Al-Harbi3Syed Ainul Abideen4Saba Ismail5Asad Ullah6Sumra Wajid Abbasi7Sajjad Ahmad8Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32611, USAInstitute of Biotechnology and Microbiology, Bacha Khan University, Charsadda 24461, PakistanDepartment of Medical Laboratory Techniques, School of Life Sciences, Dijlah University College, Baghdad 00964, IraqDepartment of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu 41477, Saudi ArabiaSchool of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200000, ChinaDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, PakistanDepartment of Health and Biological Sciences, Abasyn University, Peshawar 25000, PakistanDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, PakistanDepartment of Health and Biological Sciences, Abasyn University, Peshawar 25000, PakistanThe 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. <i>Burkholderia mallei</i> 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 <i>B. mallei</i> was designed. In completely sequenced proteomes of <i>B. mallei</i>, 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 <i>B. mallei</i>.https://www.mdpi.com/2076-393X/10/10/1580<i>Burkholderia mallei</i>multi-epitopes vaccinemolecular dynamics simulationTLR-4 |
| spellingShingle | Muhammad Irfan Saifullah Khan Alaa R. Hameed Alhanouf I. Al-Harbi Syed Ainul Abideen Saba Ismail Asad Ullah Sumra Wajid Abbasi Sajjad Ahmad Computational Based Designing of a Multi-Epitopes Vaccine against <i>Burkholderia mallei</i> Vaccines <i>Burkholderia mallei</i> multi-epitopes vaccine molecular dynamics simulation TLR-4 |
| title | Computational Based Designing of a Multi-Epitopes Vaccine against <i>Burkholderia mallei</i> |
| title_full | Computational Based Designing of a Multi-Epitopes Vaccine against <i>Burkholderia mallei</i> |
| title_fullStr | Computational Based Designing of a Multi-Epitopes Vaccine against <i>Burkholderia mallei</i> |
| title_full_unstemmed | Computational Based Designing of a Multi-Epitopes Vaccine against <i>Burkholderia mallei</i> |
| title_short | Computational Based Designing of a Multi-Epitopes Vaccine against <i>Burkholderia mallei</i> |
| title_sort | computational based designing of a multi epitopes vaccine against i burkholderia mallei i |
| topic | <i>Burkholderia mallei</i> multi-epitopes vaccine molecular dynamics simulation TLR-4 |
| url | https://www.mdpi.com/2076-393X/10/10/1580 |
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