Immunoinformatics design of multi-epitope vaccine using OmpA, OmpD and enterotoxin against non-typhoidal salmonellosis

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Abstract

Background

Non-typhoidal Salmonella (NTS) is one of the important bacteria that cause foodborne diseases and invasive infections in children and elderly people. Since NTS infection is difficult to control due to the emergence of antibiotic-resistant species and its adverse effect on immune response, the development of a vaccine against NTS would be necessary. This study aimed to develop a multi-epitope vaccine against the most prevalent serovars of NTS ( Salmonella Typhimurium, Salmonella Enteritidis) using an immunoinformatics approach and targeting OmpA, OmpD, and enterotoxin (Stn).

Results

Initially, the B cell and T cell epitopes were predicted. Then, epitopes and suitable adjuvant were assembled by molecular linkers to construct a multi-epitope vaccine. The computational tools predicted the tertiary structure, refined the tertiary structure and validated the final vaccine construct. The effectiveness of the vaccine was evaluated via molecular docking, molecular dynamics simulation, and in silico immune simulation. The vaccine model had good binding affinity and stability with MHC-I, MHC-II, and toll-like receptors (TLR-1, 2, 4) as well as activation of T cells, IgM, IgG, IFN- \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\gamma$$\end{document} and IL-2 responses. Furthermore, after codon optimization of the vaccine sequence, this sequence was cloned in E. coli plasmid vector pET-30a (+) within restriction sites of HindIII and BamHI.

Conclusions

This study, for the first time, introduced a multi-epitope vaccine based on OmpA, OmpD and enterotoxin (Stn) of NTS that could stimulate T and B cell immune responses and produced in the prokaryotic system. This vaccine was validated in-silico phase which is an essential study to reduce challenges before in vitro and in vivo studies.

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Most cited references 58

Record: found
Abstract: found
Article: not found

Structure validation by Calpha geometry: phi,psi and Cbeta deviation.

Simon C. Lovell, Ian W. Davis, W Bryan Arendall … (2003)

Geometrical validation around the Calpha is described, with a new Cbeta measure and updated Ramachandran plot. Deviation of the observed Cbeta atom from ideal position provides a single measure encapsulating the major structure-validation information contained in bond angle distortions. Cbeta deviation is sensitive to incompatibilities between sidechain and backbone caused by misfit conformations or inappropriate refinement restraints. A new phi,psi plot using density-dependent smoothing for 81,234 non-Gly, non-Pro, and non-prePro residues with B < 30 from 500 high-resolution proteins shows sharp boundaries at critical edges and clear delineation between large empty areas and regions that are allowed but disfavored. One such region is the gamma-turn conformation near +75 degrees,-60 degrees, counted as forbidden by common structure-validation programs; however, it occurs in well-ordered parts of good structures, it is overrepresented near functional sites, and strain is partly compensated by the gamma-turn H-bond. Favored and allowed phi,psi regions are also defined for Pro, pre-Pro, and Gly (important because Gly phi,psi angles are more permissive but less accurately determined). Details of these accurate empirical distributions are poorly predicted by previous theoretical calculations, including a region left of alpha-helix, which rates as favorable in energy yet rarely occurs. A proposed factor explaining this discrepancy is that crowding of the two-peptide NHs permits donating only a single H-bond. New calculations by Hu et al. [Proteins 2002 (this issue)] for Ala and Gly dipeptides, using mixed quantum mechanics and molecular mechanics, fit our nonrepetitive data in excellent detail. To run our geometrical evaluations on a user-uploaded file, see MOLPROBITY (http://kinemage.biochem.duke.edu) or RAMPAGE (http://www-cryst.bioc.cam.ac.uk/rampage). Copyright 2003 Wiley-Liss, Inc.

0 comments Cited 1109 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

PROCHECK: a program to check the stereochemical quality of protein structures

R. A. Laskowski, M. W. MacArthur, D. Moss … (1993)

Journal of Applied Crystallography, 26(2), 283-291

0 comments Cited 956 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The ClusPro web server for protein–protein docking

Dima Kozakov, David R. Hall, BING XIA … (2017)

ClusPro is a web server that performs rigid-body docking of two proteins by sampling billions of conformations. Low-energy docked structures are clustered, and centers of the largest clusters are used as likely models of the complex.

0 comments Cited 721 times – based on 0 reviews      Review now

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Author and article information

Contributors

Babak Beikzadeh:

ORCID: http://orcid.org/0000-0001-7131-9949

b.beikzadeh@bio.ui.ac.ir

Journal

Journal ID (nlm-ta): BMC Bioinformatics

Journal ID (iso-abbrev): BMC Bioinformatics

Title: BMC Bioinformatics

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2105

Publication date (Electronic): 24 February 2023

Publication date PMC-release: 24 February 2023

Publication date Collection: 2023

Volume: 24

Electronic Location Identifier: 63

Affiliations

GRID grid.411750.6, ISNI 0000 0001 0454 365X, Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, , University of Isfahan, ; Isfahan, Iran

Author information

Babak Beikzadeh http://orcid.org/0000-0001-7131-9949

Article

Publisher ID: 5183

DOI: 10.1186/s12859-023-05183-6

PMC ID: 9950014

PubMed ID: 36823524

SO-VID: dae61efc-53af-4392-9e67-1daeabb8e218

License:

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