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.

scholarly journals A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help

2017 ◽  
Vol 198 (4) ◽  
pp. 1685-1695 ◽  
Author(s):  
Meena Narayanan ◽  
Raphaela Freidl ◽  
Margarete Focke-Tejkl ◽  
Ulrike Baranyi ◽  
Thomas Wekerle ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Grass Pollen ◽  
Cell Epitope ◽  
Antibody Responses ◽  
Secondary Antibody ◽  
Epitope Peptide ◽  
B Cell Epitope ◽  
Grass Pollen Allergen ◽  
T Cell Help

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

Linear PADRE T Helper Epitope and Carbohydrate B Cell Epitope Conjugates Induce Specific High Titer IgG Antibody Responses

2000 ◽  
Vol 164 (3) ◽  
pp. 1625-1633 ◽  
Author(s):  
Jeff Alexander ◽  
Marie-France del Guercio ◽  
Ajesh Maewal ◽  
Lei Qiao ◽  
John Fikes ◽  
...  
Keyword(s):  
B Cell ◽  
High Titer ◽  
Cell Epitope ◽  
Antibody Responses ◽  
T Helper ◽  
Igg Antibody ◽  
B Cell Epitope ◽  
Helper Epitope

scholarly journals In silico analysis suggests less effective MHC-II presentation of SARS-CoV-2 RBM peptides: Implication for neutralizing antibody responses

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246731
Author(s):  
Andrea Castro ◽  
Kivilcim Ozturk ◽  
Maurizio Zanetti ◽  
Hannah Carter
Keyword(s):  
T Cell ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Cell Epitope ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Binding Motif ◽  
T Cell Epitopes ◽  
Mhc Ii ◽  
B Cell Epitope

SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.

Dominant B cell epitope from NY‐ESO‐1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker

2004 ◽  
Vol 114 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Gang Zeng ◽  
Michael E. Aldridge ◽  
Yu Wang ◽  
Allan J. Pantuck ◽  
Allen Y. Wang ◽  
...  
Keyword(s):  
B Cell ◽  
Cancer Patients ◽  
Wide Spectrum ◽  
Cell Epitope ◽  
B Cell Epitope ◽  
Potential Biomarker

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.

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