Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches

Enterobacter cloacae (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...

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Autores principales: Al-Megrin, Wafa Abdullah I., Karkashan, Alaa, Alnuqaydan, Abdullah M., Aba Alkhayl, Faris F., Alrumaihi, Faris, Almatroudi, Ahmad, Allemailem, Khaled S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227637/
https://www.ncbi.nlm.nih.gov/pubmed/35746494
http://dx.doi.org/10.3390/vaccines10060886
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author Al-Megrin, Wafa Abdullah I.
Karkashan, Alaa
Alnuqaydan, Abdullah M.
Aba Alkhayl, Faris F.
Alrumaihi, Faris
Almatroudi, Ahmad
Allemailem, Khaled S.
author_facet Al-Megrin, Wafa Abdullah I.
Karkashan, Alaa
Alnuqaydan, Abdullah M.
Aba Alkhayl, Faris F.
Alrumaihi, Faris
Almatroudi, Ahmad
Allemailem, Khaled S.
author_sort Al-Megrin, Wafa Abdullah I.
collection PubMed
description Enterobacter cloacae (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 E. cloacae 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 E. cloacae-associated illnesses, further testing in the laboratory will be required before it can be declared safe and immunogenic.
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spelling pubmed-92276372022-06-25 Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches Al-Megrin, Wafa Abdullah I. Karkashan, Alaa Alnuqaydan, Abdullah M. Aba Alkhayl, Faris F. Alrumaihi, Faris Almatroudi, Ahmad Allemailem, Khaled S. Vaccines (Basel) Article Enterobacter cloacae (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 E. cloacae 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 E. cloacae-associated illnesses, further testing in the laboratory will be required before it can be declared safe and immunogenic. MDPI 2022-06-01 /pmc/articles/PMC9227637/ /pubmed/35746494 http://dx.doi.org/10.3390/vaccines10060886 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
Al-Megrin, Wafa Abdullah I.
Karkashan, Alaa
Alnuqaydan, Abdullah M.
Aba Alkhayl, Faris F.
Alrumaihi, Faris
Almatroudi, Ahmad
Allemailem, Khaled S.
Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches
title Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches
title_full Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches
title_fullStr Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches
title_full_unstemmed Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches
title_short Design of a Multi-Epitopes Based Chimeric Vaccine against Enterobacter cloacae Using Pan-Genome and Reverse Vaccinology Approaches
title_sort design of a multi-epitopes based chimeric vaccine against enterobacter cloacae using pan-genome and reverse vaccinology approaches
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227637/
https://www.ncbi.nlm.nih.gov/pubmed/35746494
http://dx.doi.org/10.3390/vaccines10060886
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