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In silico Design of a Novel Serotype Independent Vaccine Against Streptococcus pneumoniae Based on B-cell Epitope Regions of Fibronectin Binding Protein, Choline Binding Protein D, and D-alanyl-D-alanine Carboxypeptidase

[ Vol. 16 , Issue. 4 ]

Author(s):

Shirin Tarahomjoo* and Soheila Ghaderi   Pages 372 - 381 ( 10 )

Abstract:


Background: Pneumococcal conjugate vaccines (PCVs) in the past, have been constructed via chemical coupling of pneumococcal capsules to immunogenic carrier proteins. The PCVs implementation in developing countries was prevented by their high manufacturing costs. This issue can be overcome via the development of protein-based vaccines against pneumococci. Choline binding protein D (CBPD), fibronectin binding protein (FBP), and D-alanyl-D-alanine-carboxy peptidase (DDCP) were already identified as pneumococcal surface proteins able to elicit protection against S. pneumoniae serotype 19F.

Methods: As antibody responses are necessary for protection against pneumococci, the aim of this study is, therefore, to design computationally a chimeric pneumococcal vaccine using B-cell epitope regions of CBPD, FBP, and DDCP. These regions were determined using results of Bepipred, BCPreds and CBTope programs. The most probable immunoprotective B-cell epitope region (MIBR) of each protein was identified using VaxiJen. MIBRs were highly conserved in common S. pneumoniae serotypes causing invasive pneumococcal disease worldwide. The conserved MIBRs were joined together using either flexible (Gly4Ser)2 linker or the rigid AspProArgValProSerSer linker to form antigens with molecular weights of 22.53 kDa and 22.74 kDa, respectively.

Results and Discussion: The codon optimization was done for the chimeric antigens. Analysis of mRNAs secondary structures revealed no stable hairpins at 5' ends that could interfere with antigen expression. The 3D model of the antigen possessing the flexible linker contained alpha helix, whereas several beta sheets were observed in the tertiary structure of the antigen possessing the rigid linker and it did not have any alpha helixes. Moreover, the antigen-containing the rigid linker included a beta sheet in the C-terminus of DDCP MIBR, which showed 60% residue identity to the beta sheet in the same region of the partial structure of DDCP obtained from protein data bank. However, the other antigen did not contain any similar structural elements in DDCP MIBR.

Conclusion: In silico analyses of physicochemical properties indicated that inclusion of the rigid linker instead of the flexible linker resulted in better stability of the chimeric antigen. In addition, using the rigid linker increased the probability of the protein soluble expression in Escherichia coli. Therefore, the chimeric antigen composed of conserved MIBRs joining via the rigid linker is predicted to be a suitable vaccine candidate, which could elicit protection against common pneumococcal serotypes.

Keywords:

Computational design, pneumococcal conjugate vaccines, protective epitope, protein based vaccines, Streptococcus pneumoniae, chimeric antigen.

Affiliation:

Division of Genomics and Genetic Engineering, Department of Biotechnology and Central Laboratory, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj 31975/148, Division of Central Laboratory, Department of Biotechnology and Central Laboratory, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj 31975/148

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