Development of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach

<i>Klebsiella aerogenes</i> is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce...

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Autores principales:	Ahitsham Umar, Asma Haque, Youssef Saeed Alghamdi, Mutaib M Mashraqi, Abdur Rehman, Farah Shahid, Mohsin Khurshid, Usman Ali Ashfaq
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	subtractive proteomics subunit vaccine <i>Klebsiella aerogenes</i> molecular docking Medicine R
Acceso en línea:	https://doaj.org/article/246a15ae12064a2caf63db7526cd1417
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spelling	oai:doaj.org-article:246a15ae12064a2caf63db7526cd14172021-11-25T19:11:44ZDevelopment of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach10.3390/vaccines91113732076-393Xhttps://doaj.org/article/246a15ae12064a2caf63db7526cd14172021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1373https://doaj.org/toc/2076-393X<i>Klebsiella aerogenes</i> is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce inducible chromosomal AmpC beta-lactamases, which confer high resistance. The drug resistance in <i>K. aerogenes</i> has been reported in China, Israel, Poland, Italy and the United States, with a high mortality rate (~50%). This study aims to combine immunological approaches with molecular docking approaches for three highly antigenic proteins to design vaccines against <i>K. aerogenes</i>. The synthesis of the B-cell, T-cell (CTL and HTL) and IFN-γ epitopes of the targeted proteins was performed and most conserved epitopes were chosen for future research studies. The vaccine was predicted by connecting the respective epitopes, i.e., B cells, CTL and HTL with KK, AAY and GPGPG linkers and all these were connected with N-terminal adjuvants with EAAAK linker. The humoral response of the constructed vaccine was measured through IFN-γ and B-cell epitopes. Before being used as vaccine candidate, all identified B-cell, HTL and CTL epitopes were tested for antigenicity, allergenicity and toxicity to check the safety profiles of our vaccine. To find out the compatibility of constructed vaccine with receptors, MHC-I, followed by MHC-II and TLR4 receptors, was docked with the vaccine. Lastly, in order to precisely certify the proper expression and integrity of our construct, in silico cloning was carried out. Further studies are needed to confirm the safety features and immunogenicity of the vaccine.Ahitsham UmarAsma HaqueYoussef Saeed AlghamdiMutaib M MashraqiAbdur RehmanFarah ShahidMohsin KhurshidUsman Ali AshfaqMDPI AGarticlesubtractive proteomicssubunit vaccine<i>Klebsiella aerogenes</i>molecular dockingMedicineRENVaccines, Vol 9, Iss 1373, p 1373 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	subtractive proteomics subunit vaccine <i>Klebsiella aerogenes</i> molecular docking Medicine R
spellingShingle	subtractive proteomics subunit vaccine <i>Klebsiella aerogenes</i> molecular docking Medicine R Ahitsham Umar Asma Haque Youssef Saeed Alghamdi Mutaib M Mashraqi Abdur Rehman Farah Shahid Mohsin Khurshid Usman Ali Ashfaq Development of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach
description	<i>Klebsiella aerogenes</i> is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce inducible chromosomal AmpC beta-lactamases, which confer high resistance. The drug resistance in <i>K. aerogenes</i> has been reported in China, Israel, Poland, Italy and the United States, with a high mortality rate (~50%). This study aims to combine immunological approaches with molecular docking approaches for three highly antigenic proteins to design vaccines against <i>K. aerogenes</i>. The synthesis of the B-cell, T-cell (CTL and HTL) and IFN-γ epitopes of the targeted proteins was performed and most conserved epitopes were chosen for future research studies. The vaccine was predicted by connecting the respective epitopes, i.e., B cells, CTL and HTL with KK, AAY and GPGPG linkers and all these were connected with N-terminal adjuvants with EAAAK linker. The humoral response of the constructed vaccine was measured through IFN-γ and B-cell epitopes. Before being used as vaccine candidate, all identified B-cell, HTL and CTL epitopes were tested for antigenicity, allergenicity and toxicity to check the safety profiles of our vaccine. To find out the compatibility of constructed vaccine with receptors, MHC-I, followed by MHC-II and TLR4 receptors, was docked with the vaccine. Lastly, in order to precisely certify the proper expression and integrity of our construct, in silico cloning was carried out. Further studies are needed to confirm the safety features and immunogenicity of the vaccine.
format	article
author	Ahitsham Umar Asma Haque Youssef Saeed Alghamdi Mutaib M Mashraqi Abdur Rehman Farah Shahid Mohsin Khurshid Usman Ali Ashfaq
author_facet	Ahitsham Umar Asma Haque Youssef Saeed Alghamdi Mutaib M Mashraqi Abdur Rehman Farah Shahid Mohsin Khurshid Usman Ali Ashfaq
author_sort	Ahitsham Umar
title	Development of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach
title_short	Development of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach
title_full	Development of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach
title_fullStr	Development of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach
title_full_unstemmed	Development of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach
title_sort	development of a candidate multi-epitope subunit vaccine against <i>klebsiella aerogenes</i>: subtractive proteomics and immuno-informatics approach
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/246a15ae12064a2caf63db7526cd1417
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Development of a Candidate Multi-Epitope Subunit Vaccine against <i>Klebsiella aerogenes</i>: Subtractive Proteomics and Immuno-Informatics Approach

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