In silico analysis of chimeric TF, Omp31 and BP26 fragments of Brucella melitensis for development of a multi subunit vaccine candidate

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Abstract

Objective(s): Brucellosis, especially caused by Brucella melitensis, remains one of the most common zoonotic diseases worldwide with more than 500,000 human cases reported annually. The commonly used live attenuated vaccine in ovine brucellosis prophylaxis is B. melitensis Rev1. But due to different problems caused by the administration of this vaccine, a protective subunit vaccine against B. melitensis is strongly demanded. Brucella BP26, Omp31 and TF proteins have shown a considerable potential as protective antigens for brucellosis. Chimeric proteins carrying epitopes or adjuvant sequences increase the possibility of eliciting a broad cellular or humoral immune response. In silico tools are highly suited to study, design and evaluate vaccine strategies.

Materials and Methods: In this study, a synthetic chimeric gene, encoding TF, BP26 ^93-111 and Omp31 ^48-74was designed. In order to predict the 3D structure of protein, modeling was carried out.

Results: Validation results showed that 91.1% of residues lie in favored or additional allowed region of Ramachandran plot. The epitopes in the chimeric protein are likely to induce both the B-cell and T-cell mediated immune responses.

Conclusion : The chimeric protein may be used as multi subunit for development of Brucella vaccine candidates.

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Most cited references 46

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VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines

Irini Doytchinova, Darren R. Flower (2007)

Background Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. Results Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. Conclusion VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. The server can be used on its own or in combination with alignment-based prediction methods. It is freely-available online at the URL: .

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Design of the linkers which effectively separate domains of a bifunctional fusion protein.

N Kamiya, H Ueda, R Arai … (2001)

With the aim of separating the domains of a bifunctional fusion protein, the ability of several lengths of helix-forming peptides to separate two weakly interacting beta-can domains was compared with that of flexible linkers or of a three alpha-helices bundle domain. We introduced helix-forming peptide linkers A(EAAAK)nA (n = 2-5) between two green fluorescent protein variants, EBFP and EGFP, and investigated their spectral properties. The fluorescence resonance energy transfer from EBFP to EGFP decreased as the length of the linkers increased. The circular dichroism spectra analysis suggested that the linkers form an alpha-helix and the alpha-helical contents increased as the length of the linkers increased. The results clearly suggested the ability of the helical linkers to control the distance and reduce the interference between the domains. This 'linker engineering' may open a way to the rational design of linkers which maximize the multiple functions of fusion proteins or de novo multi-domain proteins.

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Conservation and prediction of solvent accessibility in protein families.

B Rost, C. Sander (1994)

Currently, the prediction of three-dimensional (3D) protein structure from sequence alone is an exceedingly difficult task. As an intermediate step, a much simpler task has been pursued extensively: predicting 1D strings of secondary structure. Here, we present an analysis of another 1D projection from 3D structure: the relative solvent accessibility of each residue. We show that solvent accessibility is less conserved in 3D homologues than is secondary structure, and hence is predicted less accurately from automatic homology modeling; the correlation coefficient of relative solvent accessibility between 3D homologues is only 0.77, and the average accuracy of predictions based on sequence alignments is only 0.68. The latter number provides an effective upper limit on the accuracy of predicting accessibility from sequence when homology modeling is not possible. We introduce a neural network system that predicts relative solvent accessibility (projected onto ten discrete states) using evolutionary profiles of amino acid substitutions derived from multiple sequence alignments. Evaluated in a cross-validation test on 238 unique proteins, the correlation between predicted and observed relative accessibility is 0.54. Interpreted in terms of a three-state (buried, intermediate, exposed) description of relative accessibility, the fraction of correctly predicted residue states is about 58%. In absolute terms this accuracy appears poor, but given the relatively low conservation of accessibility in 3D families, the network system is not far from its likely optimal performance. The most reliably predicted fraction of the residues (50%) is predicted as accurately as by automatic homology modeling. Prediction is best for buried residues, e.g., 86% of the completely buried sites are correctly predicted as having 0% relative accessibility.

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Author and article information

Journal

Journal ID (nlm-ta): Iran J Basic Med Sci

Journal ID (iso-abbrev): Iran J Basic Med Sci

Journal ID (publisher-id): IJBMS

Title: Iranian Journal of Basic Medical Sciences

Publisher: Mashhad University of Medical Sciences (Mashhad, Iran )

ISSN (Print): 2008-3866

ISSN (Electronic): 2008-3874

Publication date (Print): March 2014

Volume: 17

Issue: 3

Pages: 172-180

Affiliations

[1 ]Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

[2 ]Applied Microbiology Research Center, Baqiyatallah Medical Science University, Tehran, Iran

Author notes

[* ]Corresponding author: Jafar Amani. Applied Microbiology Research Center, Baqiyatallah Medical Science University, Tehran, Iran. Vanak Sq. Molasadra St. Tehran, Iran. Tel: +98-21-82482568; Fax: +98-21-88068924. email: Jafar.amani@gmail.com

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Publisher ID: ijbms-17-172

PMC ID: 4016687

PubMed ID: 24847419

SO-VID: 561cdf5b-675a-484b-9ce4-f0a741004dd8

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

In silico analysis of chimeric TF, Omp31 and BP26 fragments of Brucella melitensis for development of a multi subunit vaccine candidate

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Abstract

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Malaria vaccine development

Most cited references 46

VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines

Design of the linkers which effectively separate domains of a bifunctional fusion protein.

Conservation and prediction of solvent accessibility in protein families.

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