American Journal of Microbiological Research
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American Journal of Microbiological Research. 2017, 5(6), 118-123
DOI: 10.12691/ajmr-5-6-1
Open AccessArticle

Novel Vaccines against Streptococcus pneumoniae Based on the Immunoprotective B-cell Epitope Region of Pneumococcal Choline Binding Protein D and Salmonella Enteritidis Flagellin

Shirin Tarahomjoo1, and Soheila Ghaderi2

1Division 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, Iran

2Division 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, Iran

Pub. Date: November 22, 2017

Cite this paper:
Shirin Tarahomjoo and Soheila Ghaderi. Novel Vaccines against Streptococcus pneumoniae Based on the Immunoprotective B-cell Epitope Region of Pneumococcal Choline Binding Protein D and Salmonella Enteritidis Flagellin. American Journal of Microbiological Research. 2017; 5(6):118-123. doi: 10.12691/ajmr-5-6-1

Abstract

Pneumococcal conjugate vaccines (PCVs) were constructed through chemical conjugation 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 by development of protein based vaccines against pneumococci. Antibody responses are necessary for protection against S. pneumoniae. Choline binding protein D (CBPD) was already identified as a pneumococcal surface protein able to elicit protection against S. pneumoniae and its most protective B-cell epitope region (MIBR) was determined. MIBR was highly conserved in common pneumococcal serotypes. Whole antigens are not as potent as epitope based vaccines and B-cell epitope based vaccines are more effective than whole antigen based vaccines in the prevention of infections. Bacterial flagellins are effective adjuvants that signal via Toll like receptor 5 (TLR5). The TLR5 binding site of flagellin located in the D1 domain and its proper conformation is critical for TLR5 recognition of flagellin. In the present study, therefore, we aim to design effective chimeric vaccines against pneumococci based on MIBR and flagellin of Salmonella Enteritidis (FliC) using bioinformatics tools. FliC was joined to MIBR at N-terminus (CFH), C-terminus (FCH) and the D3 domain (D3Gly202, D3Thr275). All of the constructs were immunoprotective regarding the VaxiJen score (0.8). The codon optimization for constructs was done using OPTIMIZER. Analysis of the mRNA secondary structures using Mfold tool revealed no stable hairpins at 5' ends of constructs and thus the antigens can be expressed appropriately. SCRATCH results indicated that the antigens can be expressed in the soluble form in Escherichia coli at more than 80% probability. The 3D models of antigens resulted from I-TASSER indicated the presence of alpha helix, beta sheet, turn, coil, and 310 helix as the protein structural elements. Superimposing 3D models of D1 domains of antigens with the D1 domain of FliC using FATCAT indicated no change in the D1 conformation. Therefore, FliC can exert its adjuvant effects in these constructs through TLR5 signaling. Inserting MIBR in Gly202 of FliC enhanced the protein beta sheet content remarkably, which can result in appropriate thermostability of the antigen. Our results, therefore, demonstrated that D3Gly202 is a suitable vaccine candidate, which can elicit protection against common S. pneumoniae serotypes causing invasive pneumococcal disease in children less than 5 years of age.

Keywords:
Computational design Flagellin Pneumococcal conjugate vaccines Protective epitope Protein based vaccines Streptococcus pneumoniae

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