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

Ghasemi A, Ranjbar R, Amani J - Iran J Basic Med Sci (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

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(48-74) was 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.

No MeSH data available.


Related in: MedlinePlus

Schematic model displaying the construction of TF, BP26 and Omp 31, bound together by the linkers for expression in prokaryotic cells
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Figure 1: Schematic model displaying the construction of TF, BP26 and Omp 31, bound together by the linkers for expression in prokaryotic cells

Mentions: Being reported as strong immunogens (6, 7, 9), TF protein and two peptides of B. melitensis, 27 and18 amino acids from Omp31 and BP26, respectively, were selected for the present study. Sequence comparison by ClustalW showed that these sequences were highly conserved among different strains of B.melitensis. The schematic diagram of protein domain structures with linker's sites is shown in Figure 1. Linkers, consisting EAAAK repeats and expecting to form a monomeric hydrophobic α-helix, were designed and used to separate the different domains. It has been reported that salt bridge Glu--Lys+ between the repeated Ala can stabilize helix formation. Four repeated EAAAK sequences were introduced between different domains for more flexibility and efficient separating. Arrangements of fragment junctions and linker sites are shown in Figure 1.


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

Ghasemi A, Ranjbar R, Amani J - Iran J Basic Med Sci (2014)

Schematic model displaying the construction of TF, BP26 and Omp 31, bound together by the linkers for expression in prokaryotic cells
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016687&req=5

Figure 1: Schematic model displaying the construction of TF, BP26 and Omp 31, bound together by the linkers for expression in prokaryotic cells
Mentions: Being reported as strong immunogens (6, 7, 9), TF protein and two peptides of B. melitensis, 27 and18 amino acids from Omp31 and BP26, respectively, were selected for the present study. Sequence comparison by ClustalW showed that these sequences were highly conserved among different strains of B.melitensis. The schematic diagram of protein domain structures with linker's sites is shown in Figure 1. Linkers, consisting EAAAK repeats and expecting to form a monomeric hydrophobic α-helix, were designed and used to separate the different domains. It has been reported that salt bridge Glu--Lys+ between the repeated Ala can stabilize helix formation. Four repeated EAAAK sequences were introduced between different domains for more flexibility and efficient separating. Arrangements of fragment junctions and linker sites are shown in Figure 1.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

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(48-74) was 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.

No MeSH data available.


Related in: MedlinePlus