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

2019 ◽  
Vol 16 (4) ◽  
pp. 372-381 ◽  
Author(s):  
Shirin Tarahomjoo ◽  
Soheila Ghaderi
Keyword(s):  
B Cell ◽  
In Silico ◽  
Binding Protein ◽  
Cell Epitope ◽  
Alpha Helix ◽  
Beta Sheet ◽  
Epitope Region ◽  
B Cell Epitope ◽  
Fibronectin Binding Protein ◽  
Fibronectin Binding

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.

scholarly journals An Introduction to B-Cell Epitope Mapping and In Silico Epitope Prediction

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Lenka Potocnakova ◽  
Mangesh Bhide ◽  
Lucia Borszekova Pulzova
Keyword(s):  
B Cell ◽  
In Silico ◽  
Epitope Mapping ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Diagnostic Tools ◽  
Accurate Identification ◽  
B Cell Epitopes ◽  
Epitope Identification ◽  
B Cell Epitope

Identification of B-cell epitopes is a fundamental step for development of epitope-based vaccines, therapeutic antibodies, and diagnostic tools. Epitope-based antibodies are currently the most promising class of biopharmaceuticals. In the last decade, in-depth in silico analysis and categorization of the experimentally identified epitopes stimulated development of algorithms for epitope prediction. Recently, various in silico tools are employed in attempts to predict B-cell epitopes based on sequence and/or structural data. The main objective of epitope identification is to replace an antigen in the immunization, antibody production, and serodiagnosis. The accurate identification of B-cell epitopes still presents major challenges for immunologists. Advances in B-cell epitope mapping and computational prediction have yielded molecular insights into the process of biorecognition and formation of antigen-antibody complex, which may help to localize B-cell epitopes more precisely. In this paper, we have comprehensively reviewed state-of-the-art experimental methods for B-cell epitope identification, existing databases for epitopes, and novel in silico resources and prediction tools available online. We have also elaborated new trends in the antibody-based epitope prediction. The aim of this review is to assist researchers in identification of B-cell epitopes.

scholarly journals Linear and Conformational B Cell Epitope Prediction of the HER 2 ECD-Subdomain III by in silico Methods

2012 ◽  
Vol 13 (7) ◽  
pp. 3053-3059 ◽  
Author(s):  
Manijeh Mahdavi ◽  
Hassan Mohabatkar ◽  
Mehrnaz Keyhanfar ◽  
Abbas Jafarian Dehkordi ◽  
Mohammad Rabbani
Keyword(s):  
B Cell ◽  
In Silico ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
B Cell Epitope ◽  
Her 2 ◽  
In Silico Methods

scholarly journals Polymorphism of 41 kD Flagellin Gene and Its Human B-Cell Epitope in Borrelia burgdorferi Strains of China

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Huixin Liu ◽  
Wei Liu ◽  
Xuexia Hou ◽  
Lin Zhang ◽  
Qin Hao ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
B Cell ◽  
Early Stage ◽  
Cell Epitope ◽  
Gene Encoding ◽  
Epitope Region ◽  
B Cell Epitopes ◽  
B Cell Epitope ◽  
Human B Cell

The 41 kD flagellin of Borrelia burgdorferi (B. burgdorferi) is a major component of periplasmic flagellar filament core and a good candidate for serodiagnosis in early stage of Lyme disease. Here, we chose 89 B. burgdorferi strains in China, amplified the gene encoding the 41 kD flagellin, and compared the sequences. The results showed that genetic diversity presented in the 41 kD flagellin genes of all 89 strains among the four genotypes of B. burgdorferi, especially in the genotype of B. garinii. Some specific mutation sites for each genotype of the 41 kD flagellin genes were found, which could be used for genotyping B. burgdorferi strains in China. Human B-cell epitope analysis showed that thirteen of 15 nonsynonymous mutations occurred in the epitope region of 41 kD flagellin and thirty of 42 B-cell epitopes were altered due to all 13 nonsynonymous mutations in the epitope region, which may affect the function of the antigen. Nonsynonymous mutations and changed human B-cell epitopes exist in 41 kD flagellin of B. burgdorferi sensu lato strains; these changes should be considered in serodiagnosis of Lyme disease.

An Immunodominant, Cross-Reactive B-Cell Epitope Region Is Located at the C-Terminal Part of the Hamster Polyomavirus Major Capsid Protein VP1

2000 ◽  
Vol 13 (4) ◽  
pp. 533-545 ◽  
Author(s):  
HASSEN SIRAY ◽  
CORNELIUS FRÖMMEL ◽  
TATYANA VORONKOVA ◽  
STEFANIE HAHN ◽  
WOLFGANG ARNOLD ◽  
...  
Keyword(s):  
B Cell ◽  
Capsid Protein ◽  
Major Capsid Protein ◽  
Cell Epitope ◽  
Terminal Part ◽  
Epitope Region ◽  
B Cell Epitope ◽  
Hamster Polyomavirus ◽  
Capsid Protein Vp1

Sequence Analysis and B Cell Epitope Prediction of Duck Hepatitis A Virus 1 VP1 Gene

2013 ◽  
Vol 647 ◽  
pp. 214-219
Author(s):  
Xing Jian Wen ◽  
An Chun Cheng ◽  
Ming Shu Wang
Keyword(s):  
B Cell ◽  
Hepatitis A Virus ◽  
Phylogenetic Analyses ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Alpha Helix ◽  
Vp1 Gene ◽  
Vp1 Protein ◽  
Duck Hepatitis ◽  
B Cell Epitope

Molecular characterization and phylogenetic analysis of the DHAV-1 VP1 gene, structure and biological function of the VP1 protein were analyzed by using the programs of the DNAstar software ,MEGA software and other bioinformatics software on the line. The nucleotide sequence homologies among and the amino acids homologies of the VP1 gene of DHAV H stain with other 13 DHAV-1 strains in the GenBank were 92.54%-99.86% and 93.75%-99.57%.The putative secondary structure of the VP1 protein contained 10.08% H(alpha helix), 38.24% E(beta-sheet), 51.68%L(loop/coil), Protein can be classified as mixed. The results showed that the B cell epitopes of the VP1 protein were located at the C-terminal 131-136, and 209-218 regions according to Kyte-Doolitte method, Emini method,Karlus-Schulz method, and Jameson-Wolf method implemented in Protean program of DNAStar 7.The VP1 protein in the surface of the virus most exposed, it is to decide the major components of the effects of the virus of Picornaviridae. The VP1 protein of DHAV is a good biomaterial for vaccine research, and genetic and phylogenetic analyses of the VP1 and the B cell epitope prediction can help us to develop multi-epitope vaccine against DHAV variant viruses infections.

scholarly journals Deimmunization of flagellin for repeated administration as a vaccine adjuvant

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Koemchhoy Khim ◽  
Yong Jun Bang ◽  
Sao Puth ◽  
Yoonjoo Choi ◽  
Youn Suhk Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Vibrio Vulnificus ◽  
Wide Spectrum ◽  
Cell Epitope ◽  
Repeated Administration ◽  
Antibody Responses ◽  
Vaccine Antigen ◽  
Epitope Region ◽  
B Cell Epitope

AbstractFlagellin, a protein-based Toll-like receptor agonist, is a versatile adjuvant applicable to wide spectrum of vaccines and immunotherapies. Given reiterated treatments of immunogenic biopharmaceuticals should lead to antibody responses precluding repeated administration, the development of flagellin not inducing specific antibodies would greatly expand the chances of clinical applications. Here we computationally identified immunogenic regions in Vibrio vulnificus flagellin B and deimmunized by simply removing a B cell epitope region. The recombinant deimmunized FlaB (dFlaB) maintains stable TLR5-stimulating activity. Multiple immunization of dFlaB does not induce FlaB-specific B cell responses in mice. Intranasally co-administered dFlaB with influenza vaccine enhanced strong Ag-specific immune responses in both systemic and mucosal compartments devoid of FlaB-specific Ab production. Notably, dFlaB showed better protective immune responses against lethal viral challenge compared with wild type FlaB. The deimmunizing B cell epitope deletion did not compromise stability and adjuvanticity, while suppressing unwanted antibody responses that may negatively affected vaccine antigen-directed immune responses in repeated vaccinations. We explain the underlying mechanism of deimmunization by employing molecular dynamics analysis.

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