Design of a Multi-Epitopes Based Chimeric Vaccine against <i>Enterobacter cloacae</i> Using Pan-Genome and Reverse Vaccinology Approaches
<i>Enterobacter cloacae</i> (EC) is a significant emerging pathogen that is occasionally associated with lung infection, surgical site infection, urinary infection, sepsis, and outbreaks in neonatal intensive care units. In light of the fact that there is currently no approved vaccine or...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/10/6/886 |
| _version_ | 1797481656657903616 |
|---|---|
| author | Wafa Abdullah I. Al-Megrin Alaa Karkashan Abdullah M. Alnuqaydan Faris F. Aba Alkhayl Faris Alrumaihi Ahmad Almatroudi Khaled S. Allemailem |
| author_facet | Wafa Abdullah I. Al-Megrin Alaa Karkashan Abdullah M. Alnuqaydan Faris F. Aba Alkhayl Faris Alrumaihi Ahmad Almatroudi Khaled S. Allemailem |
| author_sort | Wafa Abdullah I. Al-Megrin |
| collection | DOAJ |
| description | <i>Enterobacter cloacae</i> (EC) is a significant emerging pathogen that is occasionally associated with lung infection, surgical site infection, urinary infection, sepsis, and outbreaks in neonatal intensive care units. In light of the fact that there is currently no approved vaccine or therapeutic option for the treatment of EC, the current study was developed to concentrate on applications based on modern computational approaches to design a multi-epitope-based <i>E. cloacae</i> peptide vaccine (MEBEPV) expressing the antigenic determinants prioritized from the EC genome. Integrated computational analyses identified two potential protein targets (phosphoporin protein-PhoE and putative outer-membrane porin protein) for further exploration on the basis of pangenome subtractive proteomics and immunoinformatic in-depth examination of the core proteomes. Then, a multi-epitope peptide vaccine was designed, which comprised shortlisted epitopes that were capable of eliciting both innate and adaptive immunity, as well as the cholera toxin’s B-subunit, which was used as an adjuvant in the vaccine formulation. To ensure maximum expression, the vaccine’s 3D structure was developed and the loop was refined, improving the stability by disulfide engineering, and the physicochemical characteristics of the recombinant vaccine sequence were found to be ideal for both in vitro and in vivo experimentation. Blind docking was then used for the prediction of the MEBEPV predominant blinding mode with MHCI, MHCII, and TLR3 innate immune receptors, with lowest global energy of −18.64 kJ/mol, −48.25 kJ/mol, and −5.20 kJ/mol for MHC-I, MHC-II, and TLR-4, respectively, with docked complexes considered for simulation. In MD and MMGBSA investigations, the docked models of MEBEPV-TLR3, MEBEPV-MHCI, and MEBEPV-MHCII were found to be stable during the course of the simulation. MM-GBSA analysis calculated −122.17 total net binding free energies for the TLR3-vaccine complex, −125.4 for the MHC I-vaccine complex, and −187.94 for the MHC II-vaccine complex. Next, MM-PBSA analysis calculated −115.63 binding free energy for the TLR3-vaccine complex, −118.19 for the MHC I-vaccine complex, and −184.61 for the MHC II-vaccine complex. When the vaccine was tested in silico, researchers discovered that it was capable of inducing both types of immune responses (cell mediated and humoral) at the same time. Even though the suggested MEBEPV has the potential to be a powerful contender against <i>E. cloacae</i>-associated illnesses, further testing in the laboratory will be required before it can be declared safe and immunogenic. |
| first_indexed | 2024-03-09T22:17:44Z |
| format | Article |
| id | doaj.art-ec305fbf112047a493bbd23273fad721 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T22:17:44Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-ec305fbf112047a493bbd23273fad7212023-11-23T19:20:53ZengMDPI AGVaccines2076-393X2022-06-0110688610.3390/vaccines10060886Design of a Multi-Epitopes Based Chimeric Vaccine against <i>Enterobacter cloacae</i> Using Pan-Genome and Reverse Vaccinology ApproachesWafa Abdullah I. Al-Megrin0Alaa Karkashan1Abdullah M. Alnuqaydan2Faris F. Aba Alkhayl3Faris Alrumaihi4Ahmad Almatroudi5Khaled S. Allemailem6Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Biology, College of Sciences, University of Jeddah, Jeddah 21959, Saudi Arabia Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia<i>Enterobacter cloacae</i> (EC) is a significant emerging pathogen that is occasionally associated with lung infection, surgical site infection, urinary infection, sepsis, and outbreaks in neonatal intensive care units. In light of the fact that there is currently no approved vaccine or therapeutic option for the treatment of EC, the current study was developed to concentrate on applications based on modern computational approaches to design a multi-epitope-based <i>E. cloacae</i> peptide vaccine (MEBEPV) expressing the antigenic determinants prioritized from the EC genome. Integrated computational analyses identified two potential protein targets (phosphoporin protein-PhoE and putative outer-membrane porin protein) for further exploration on the basis of pangenome subtractive proteomics and immunoinformatic in-depth examination of the core proteomes. Then, a multi-epitope peptide vaccine was designed, which comprised shortlisted epitopes that were capable of eliciting both innate and adaptive immunity, as well as the cholera toxin’s B-subunit, which was used as an adjuvant in the vaccine formulation. To ensure maximum expression, the vaccine’s 3D structure was developed and the loop was refined, improving the stability by disulfide engineering, and the physicochemical characteristics of the recombinant vaccine sequence were found to be ideal for both in vitro and in vivo experimentation. Blind docking was then used for the prediction of the MEBEPV predominant blinding mode with MHCI, MHCII, and TLR3 innate immune receptors, with lowest global energy of −18.64 kJ/mol, −48.25 kJ/mol, and −5.20 kJ/mol for MHC-I, MHC-II, and TLR-4, respectively, with docked complexes considered for simulation. In MD and MMGBSA investigations, the docked models of MEBEPV-TLR3, MEBEPV-MHCI, and MEBEPV-MHCII were found to be stable during the course of the simulation. MM-GBSA analysis calculated −122.17 total net binding free energies for the TLR3-vaccine complex, −125.4 for the MHC I-vaccine complex, and −187.94 for the MHC II-vaccine complex. Next, MM-PBSA analysis calculated −115.63 binding free energy for the TLR3-vaccine complex, −118.19 for the MHC I-vaccine complex, and −184.61 for the MHC II-vaccine complex. When the vaccine was tested in silico, researchers discovered that it was capable of inducing both types of immune responses (cell mediated and humoral) at the same time. Even though the suggested MEBEPV has the potential to be a powerful contender against <i>E. cloacae</i>-associated illnesses, further testing in the laboratory will be required before it can be declared safe and immunogenic.https://www.mdpi.com/2076-393X/10/6/886<i>Enterobacter cloaca</i>pangenome subtractive proteomicsimmunoinformaticmolecular dockingmolecular dynamic simulationsbinding free energies |
| spellingShingle | Wafa Abdullah I. Al-Megrin Alaa Karkashan Abdullah M. Alnuqaydan Faris F. Aba Alkhayl Faris Alrumaihi Ahmad Almatroudi Khaled S. Allemailem Design of a Multi-Epitopes Based Chimeric Vaccine against <i>Enterobacter cloacae</i> Using Pan-Genome and Reverse Vaccinology Approaches Vaccines <i>Enterobacter cloaca</i> pangenome subtractive proteomics immunoinformatic molecular docking molecular dynamic simulations binding free energies |
| title | Design of a Multi-Epitopes Based Chimeric Vaccine against <i>Enterobacter cloacae</i> Using Pan-Genome and Reverse Vaccinology Approaches |
| title_full | Design of a Multi-Epitopes Based Chimeric Vaccine against <i>Enterobacter cloacae</i> Using Pan-Genome and Reverse Vaccinology Approaches |
| title_fullStr | Design of a Multi-Epitopes Based Chimeric Vaccine against <i>Enterobacter cloacae</i> Using Pan-Genome and Reverse Vaccinology Approaches |
| title_full_unstemmed | Design of a Multi-Epitopes Based Chimeric Vaccine against <i>Enterobacter cloacae</i> Using Pan-Genome and Reverse Vaccinology Approaches |
| title_short | Design of a Multi-Epitopes Based Chimeric Vaccine against <i>Enterobacter cloacae</i> Using Pan-Genome and Reverse Vaccinology Approaches |
| title_sort | design of a multi epitopes based chimeric vaccine against i enterobacter cloacae i using pan genome and reverse vaccinology approaches |
| topic | <i>Enterobacter cloaca</i> pangenome subtractive proteomics immunoinformatic molecular docking molecular dynamic simulations binding free energies |
| url | https://www.mdpi.com/2076-393X/10/6/886 |
| work_keys_str_mv | AT wafaabdullahialmegrin designofamultiepitopesbasedchimericvaccineagainstienterobactercloacaeiusingpangenomeandreversevaccinologyapproaches AT alaakarkashan designofamultiepitopesbasedchimericvaccineagainstienterobactercloacaeiusingpangenomeandreversevaccinologyapproaches AT abdullahmalnuqaydan designofamultiepitopesbasedchimericvaccineagainstienterobactercloacaeiusingpangenomeandreversevaccinologyapproaches AT farisfabaalkhayl designofamultiepitopesbasedchimericvaccineagainstienterobactercloacaeiusingpangenomeandreversevaccinologyapproaches AT farisalrumaihi designofamultiepitopesbasedchimericvaccineagainstienterobactercloacaeiusingpangenomeandreversevaccinologyapproaches AT ahmadalmatroudi designofamultiepitopesbasedchimericvaccineagainstienterobactercloacaeiusingpangenomeandreversevaccinologyapproaches AT khaledsallemailem designofamultiepitopesbasedchimericvaccineagainstienterobactercloacaeiusingpangenomeandreversevaccinologyapproaches |