Core proteome mediated therapeutic target mining and multi-epitope vaccine design for Helicobacter pylori.


Journal

Genomics
ISSN: 1089-8646
Titre abrégé: Genomics
Pays: United States
ID NLM: 8800135

Informations de publication

Date de publication:
09 2020
Historique:
received: 21 05 2020
revised: 13 06 2020
accepted: 15 06 2020
pubmed: 21 6 2020
medline: 18 8 2021
entrez: 21 6 2020
Statut: ppublish

Résumé

Helicobacter pylori is a Gram-negative spiral-shaped bacterium that infects half of the human population worldwide and causes chronic inflammation. In the present study, we used the art of computational biology for therapeutic drug targets identification and a multi-epitope vaccine against multi-strains of H. pylori. For drug target identification, we used different tools and softwares to identify human non-homologous but pathogen essential proteins, with virulent properties and involved in unique metabolic pathways of H. pylori. For this purpose, the core proteome of 84 strains of H. pylori was retrieved from EDGAR 2.3 database. There were 59,808 proteins sequences in these strains. Duplicates and paralogous protein sequence removal was followed by human non-homologous protein miningPathogen essential and virulent proteins were subjected to pathway analysis Subcellular localization of the virulent proteins was predicted and druggability was also checked, leading to 30 druggable targets based on their similarity with the approved drug targets in Drugbank. For immunoinformatics analysis, we selected two outer membrane proteins (HPAKL86_RS06305 and HPSNT_RS00950) and subjected to determined immunogenic B and T-Cell epitopes. The B and T-Cell overlapped epitopes were selected to design 9 different vaccine constructs by using linkers and adjuvants. Least allergenic and most antigenic construct (C-8) was selected as a promiscuous vaccine to elicit host immune response. Cloning and in silico expression of the constructed vaccine (C-8) was done to produce a clone having the desired (gene) vaccine construct. In conclusion, the prioritized therapeutic targets for 84 strains of H.pylori will be useful for future therapy design. Vaccine design may also prove useful in the quest for targeting multi-strains of H. pylori in patients.

Identifiants

pubmed: 32562830
pii: S0888-7543(20)30623-6
doi: 10.1016/j.ygeno.2020.06.026
pii:
doi:

Substances chimiques

Bacterial Proteins 0
Bacterial Vaccines 0
Epitopes, B-Lymphocyte 0
Epitopes, T-Lymphocyte 0
Proteome 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3473-3483

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare no conflicts of interest in preparing this article.

Auteurs

Noor Rahman (N)

H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: noorbiochemist@gmail.com.

Amar Ajmal (A)

Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, KP, Pakistan.

Fawad Ali (F)

Department of Biochemistry, Hazara University, Mansehra, Pakistan.

Luca Rastrelli (L)

Dipartimento di Farmacia, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, SA, Italy.

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Classifications MeSH