scholarly journals Towards a Vaccine Against Rheumatic Fever

2006 ◽  
Vol 13 (2-4) ◽  
pp. 125-132 ◽  
Author(s):  
L. Guilherme ◽  
K. C. Faé ◽  
F. Higa ◽  
L. Chaves ◽  
S. E. Oshiro ◽  
...  
Keyword(s):  
Amino Acid ◽  
Autoimmune Disease ◽  
Rheumatic Fever ◽  
B Cell ◽  
Cell Epitope ◽  
M Protein ◽  
Bacterial Invasion ◽  
Amino Acid Residues ◽  
Terminal Portion ◽  
B Cell Epitopes

Rheumatic fever (RF) is an autoimmune disease which affects more than 20 million children in developing countries. It is triggered byStreptococcus pyogenesthroat infection in untreated susceptible individuals. Carditis, the most serious manifestation of the disease, leads to severe and permanent valvular lesions, causing chronic rheumatic heart disease (RHD). We have been studying the mechanisms leading to pathological autoimmunity in RF/RHD for the last 15 years. Our studies allowed us a better understanding of the cellular and molecular pathogenesis of RHD, paving the way for the development of a safe vaccine for a post-infection autoimmune disease. We have focused on the search for protective T and B cell epitopes by testing 620 human blood samples against overlapping peptides spanning 99 residues of the C-terminal portion of the M protein, differing by one amino acid residue. We identified T and B cell epitopes with 22 and 25 amino acid residues, respectively. Although these epitopes were from different regions of the C-terminal portion of the M protein, they showed an identical core of 16 amino acid residues. Antibodies against the B cell epitope inhibited bacterial invasion/adhesionin vitro. Our results strongly indicated that the selected T and B cell epitopes could potentially be protective againstS. pyogenes.

scholarly journals Novel differential linear B-cell epitopes to identify Zika and dengue virus infections in patients

2019 ◽  
Author(s):  
Siti Naqiah Amrun ◽  
Wearn-Xin Yee ◽  
Farhana Abu Bakar ◽  
Bernett Lee ◽  
Yiu-Wing Kam ◽  
...  
Keyword(s):  
B Cell ◽  
Neutralizing Antibodies ◽  
Cell Epitope ◽  
Structural Similarity ◽  
Amino Acid Residues ◽  
Virus Infections ◽  
Protein Amino Acid ◽  
B Cell Epitopes ◽  
Diagnostic Standards ◽  
Linear B

AbstractBackgroundRecent Zika virus (ZIKV) outbreaks challenged existing laboratory diagnostic standards, especially for serology-based methods. Due to the genetic and structural similarity of ZIKV with other flaviviruses, this results in cross-reactive antibodies which confounds serological interpretations.MethodsPlasma from Singapore ZIKV patients was screened longitudinally for antibody responses and neutralizing capacities against ZIKV. Samples from healthy controls, ZIKV and DENV patients were further assessed using ZIKV and DENV peptides of precursor membrane (prM), envelope (E) or non-structural 1 (NS1) viral proteins in a peptide-based ELISA for epitope identification. Identified epitopes were re-validated and diagnostically evaluated using sera of patients with DENV, bacteria or unknown infections from Thailand.ResultsLong-lasting ZIKV-neutralizing antibodies were elicited during ZIKV infection. Thirteen potential linear B-cell epitopes were identified and of these, four common flavivirus, three ZIKV-specific, and one DENV-specific differential epitopes had more than 50% sensitivities and specificities. Notably, ZIKV-specific peptide 26 on domain I/II of E protein (amino acid residues 271-288) presented 80% sensitivity and 85.7% specificity. Importantly, the differential epitopes also showed significance in differentiating non-flavivirus patient samples.ConclusionsLinear B-cell epitope candidates to differentiate ZIKV and DENV infections were identified, providing the first step towards the design of a much-needed serology-based assay.

scholarly journals Identification of Continuous B-Cell Epitopes on the Protein Moiety of the 58-Kilodalton Cell Wall Mannoprotein ofCandida albicans Belonging to a Family of Immunodominant Fungal Antigens

2001 ◽  
Vol 69 (5) ◽  
pp. 2909-2919 ◽  
Author(s):  
Angel Viudes ◽  
Sofia Perea ◽  
Jose L. Lopez-Ribot
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Amino Acid Residues ◽  
B Cell Epitopes ◽  
C Terminus ◽  
Elisa Testing ◽  
Fungal Antigens ◽  
Protein Moiety

ABSTRACT The 58-kiloDalton mannoprotein (mp58) on the surface ofCandida albicans is highly immunogenic, is expressed by allC. albicans isolates tested, and elicits strong antibody responses during candidiasis. It belongs to a family of immunodominant fungal antigens with representatives also in different species ofAspergillus. The amino acid sequence of the protein portion of mp58 as deduced from the DNA sequence of its encoding gene (FBP1/PRA1) was used to synthesize a complete set of overlapping dodecapeptides (overlap, 7; offset, 5) covalently attached to the surface of derivatized polyethylene pins. The pin-coupled peptides were used in a modified enzyme-linked immunosorbent assay (ELISA) to identify continuous epitopes recognized by a number of antiserum preparations containing anti-mp58 antibodies. This comprehensive epitope-scanning study revealed the presence of multiple immunoreactive continuous B-cell epitopes within the protein sequence. Regions of increased reactivity included both the amino and carboxy termini of the mature protein (encompassing amino acid residues 16 to 50 and 286 to 299, respectively) and four internal regions spanning amino acids at positions 66 to 92, 121 to 142, 148 to 192, and 211 to 232. Further delineation of epitopic regions and identification of the boundaries of the antigenic sites was performed upon ELISA testing with a second Pepset consisting of completely overlapping 8-mer peptides spanning these reactive regions in the protein moiety of mp58. The highly reactive epitopic region at the C terminus of the protein was further evaluated using both window net and replacement net analyses. A synthetic peptide corresponding to the last 10 amino acid residues at the C terminus of the protein was immunogenic when injected into mice after being coupled to a carrier protein. Moreover, antibodies in the resulting sera specifically recognized the homologus mp58 in ELISAs and immunoblot assays. Delineation of the antibody responses to mp58 could provide the basis for the development of novel immunity-based prophylactic, therapeutic, and diagnostic techniques for the management of candidiasis.

scholarly journals Multiple Distinct Sets of Stereotyped Antigen Receptors Indicate a Role for Antigen in Promoting Chronic Lymphocytic Leukemia

2004 ◽  
Vol 200 (4) ◽  
pp. 519-525 ◽  
Author(s):  
Bradley T. Messmer ◽  
Emilia Albesiano ◽  
Dimitar G. Efremov ◽  
Fabio Ghiotto ◽  
Steven L. Allen ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Structural Features ◽  
Lymphocytic Leukemia ◽  
Cell Subpopulation ◽  
Amino Acid Residues ◽  
Antigen Receptors ◽  
Region Gene ◽  
V Region ◽  
Unique Amino Acid

Previous studies suggest that the diversity of the expressed variable (V) region repertoire of the immunoglobulin (Ig)H chain of B-CLL cells is restricted. Although limited examples of marked constraint in the primary structure of the H and L chain V regions exist, the possibility that this level of restriction is a general principle in this disease has not been accepted. This report describes five sets of patients, mostly with unmutated or minimally mutated IgV genes, with strikingly similar B cell antigen receptors (BCRs) arising from the use of common H and L chain V region gene segments that share CDR3 structural features such as length, amino acid composition, and unique amino acid residues at recombination junctions. Thus, a much more striking degree of structural restriction of the entire BCR and a much higher frequency of receptor sharing exists among patients than appreciated previously. The data imply that either a significant fraction of B-CLL cells was selected by a limited set of antigenic epitopes at some point in their development and/or that they derive from a distinct B cell subpopulation with limited Ig V region diversity. These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy.

scholarly journals Data curation to improve the pattern recognition performance of B-cell epitope prediction by support vector machine

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Li Cen Lim ◽  
Yee Ying Lim ◽  
Yee Siew Choong
Keyword(s):  
Pattern Recognition ◽  
Support Vector Machine ◽  
B Cell ◽  
Recognition Performance ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Support Vector ◽  
B Cell Epitopes ◽  
Prediction Module ◽  
B Cell Epitope

Abstract B-cell epitope will be recognized and attached to the surface of receptors in B-lymphocytes to trigger immune response, thus are the vital elements in the field of epitope-based vaccine design, antibody production and therapeutic development. However, the experimental approaches in mapping epitopes are time consuming and costly. Computational prediction could offer an unbiased preliminary selection to reduce the number of epitopes for experimental validation. The deposited B-cell epitopes in the databases are those with experimentally determined positive/negative peptides and some are ambiguous resulted from different experimental methods. Prior to the development of B-cell epitope prediction module, the available dataset need to be handled with care. In this work, we first pre-processed the B-cell epitope dataset prior to B-cell epitopes prediction based on pattern recognition using support vector machine (SVM). By using only the absolute epitopes and non-epitopes, the datasets were classified into five categories of pathogen and worked on the 6-mers peptide sequences. The pre-processing of the datasets have improved the B-cell epitope prediction performance up to 99.1 % accuracy and showed significant improvement in cross validation results. It could be useful when incorporated with physicochemical propensity ranking in the future for the development of B-cell epitope prediction module.

Prediction of linear B-cell epitopes using amino acid pair antigenicity scale

Amino Acids ◽  
2007 ◽  
Vol 33 (3) ◽  
pp. 423-428 ◽  
Author(s):  
J. Chen ◽  
H. Liu ◽  
J. Yang ◽  
K.-C. Chou
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Amino Acid Pair ◽  
B Cell Epitopes ◽  
Linear B

scholarly journals B-Cell Epitope Discovery: The First Protein Flexibility-Based Algorithm – Zika Virus Conserved Epitope Demonstration

2020 ◽  
Author(s):  
Daniel W. Biner ◽  
Jason S. Grosch ◽  
Peter J. Ortoleva
Keyword(s):  
B Cell ◽  
Zika Virus ◽  
Clustering Algorithm ◽  
Cell Epitope ◽  
Protein Flexibility ◽  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
B Cell Epitopes ◽  
Enveloped Virus ◽  
Epitope Discovery

<p></p><p>Antibody-antigen interaction – at antigenic local environments called B-cell epitopes – is a prominent mechanism for neutralization of infection. Effective mimicry, and display, of B-cell epitopes is key to vaccine design. Here, a physical approach is evaluated for the discovery of epitopes which evolve slowly over closely related pathogens (conserved epitopes). The approach is 1) protein flexibility-based and 2) demonstrated with clinically relevant enveloped viruses, simulated via molecular dynamics. The approach is validated against 1) seven structurally characterized enveloped virus epitopes which evolved the least (out of thirty-eight enveloped virus-antibody structures) and 2) eight preexisting epitope and peptide discovery algorithms. Rationale for a new benchmarking scheme is presented. A data-driven epitope clustering algorithm is introduced. The prediction of eleven Zika virus epitopes (for future exploration on recombinant vaccine technologies) is demonstrated. For the first time, protein flexibility is shown to outperform solvent accessible surface area as an epitope discovery metric.</p><p></p>

scholarly journals Immunodominant and neutralizing linear B cell epitopes spanning the spike and membrane proteins of Porcine Epidemic Diarrhea Virus

2021 ◽  
Author(s):  
Kanokporn Polyiam ◽  
Marasri Ruengjitchatchawalya ◽  
Phenjun Mekvichitsaeng ◽  
Kampon Kaeoket ◽  
Tawatchai Hoonsuwan ◽  
...  
Keyword(s):  
B Cell ◽  
Porcine Epidemic Diarrhea Virus ◽  
M Protein ◽  
B Cell Epitopes ◽  
Diarrhea Virus ◽  
M Proteins ◽  
Porcine Epidemic Diarrhea ◽  
Neutralizing Epitopes ◽  
Immunodominant Epitopes ◽  
Linear B

AbstractPorcine Epidemic Diarrhea Virus (PEDV) is the causative agent of PED, an enteric disease that causes high mortality rates in piglets. PEDV is an alphacoronavirus that has high genetic diversity. Insights into neutralizing B cell epitopes of all genetically diverse PEDV strains are of importance, particularly for designing a vaccine that can provide broad protection against PEDV. In this work, we aimed to explore the landscape of linear B cell epitopes on the spike (S) and membrane (M) proteins of global PEDV strains. All amino acid sequences of the PEDV S and M proteins were retrieved from the NCBI database and grouped. Immunoinformatics-based methods were next developed and used to identify putative linear B cell epitopes from 14 and 5 consensus sequences generated from distinct groups of the S and M proteins, respectively. ELISA testing predicted peptides with PEDV-positive sera revealed 9 novel immunodominant epitopes on the S protein. Importantly, 7 of these novel immunodominant epitopes and other subdominant epitopes were demonstrated to be neutralizing epitopes by neutralization-inhibition assay. Additionally, our study shows the first time that M protein is also the target of neutralizing antibodies as 7 neutralizing epitopes in the M protein were identified. Conservancy analysis revealed that epitopes in the S1 subunit are more variable than those in the S2 subunit and M protein. In this study, we offer the immunoinformatics approach for linear B cell epitope identification and a more complete profile of linear B cell epitopes across the PEDV S and M proteins, which may contribute to the development of a greater PEDV vaccine as well as peptide-based immunoassays.

scholarly journals The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 432 ◽  
Author(s):  
Jessica M. van Loben Sels ◽  
Kim Y. Green
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
P Domain ◽  
Capsid Protein Vp1 ◽  
Murine Noroviruses ◽  
Acute Nonbacterial Gastroenteritis ◽  
Insight Into

Human norovirus (HuNoV) is the leading cause of acute nonbacterial gastroenteritis. Vaccine design has been confounded by the antigenic diversity of these viruses and a limited understanding of protective immunity. We reviewed 77 articles published since 1988 describing the isolation, function, and mapping of 307 unique monoclonal antibodies directed against B cell epitopes of human and murine noroviruses representing diverse Genogroups (G). Of these antibodies, 91, 153, 21, and 42 were reported as GI-specific, GII-specific, MNV GV-specific, and G cross-reactive, respectively. Our goal was to reconstruct the antigenic topology of noroviruses in relationship to mapped epitopes with potential for therapeutic use or inclusion in universal vaccines. Furthermore, we reviewed seven published studies of norovirus T cell epitopes that identified 18 unique peptide sequences with CD4- or CD8-stimulating activity. Both the protruding (P) and shell (S) domains of the major capsid protein VP1 contained B and T cell epitopes, with the majority of neutralizing and HBGA-blocking B cell epitopes mapping in or proximal to the surface-exposed P2 region of the P domain. The majority of broadly reactive B and T cell epitopes mapped to the S and P1 arm of the P domain. Taken together, this atlas of mapped B and T cell epitopes offers insight into the promises and challenges of designing universal vaccines and immunotherapy for the noroviruses.

scholarly journals Anti-M monoclonal antibodies cross-reacting with variant Mg antigen: an example of modulation of antigenic properties of peptide by its glycosylation

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2340-2345 ◽  
Author(s):  
E Jaskiewicz ◽  
M Czerwinski ◽  
D Syper ◽  
E Lisowska
Keyword(s):  
Monoclonal Antibodies ◽  
Amino Acid ◽  
Blood Group ◽  
Polypeptide Chain ◽  
Protein Glycosylation ◽  
Glycophorin A ◽  
Amino Acid Residues ◽  
Terminal Portion ◽  
Peptide Analogs ◽  
Antigenic Properties

Abstract Some monoclonal antibodies (MoAbs) directed against blood group M- related epitope of glycophorin A (GPA) were found to agglutinate rare variant erythrocytes carrying GPA of Mg type. In contradistinction to normal GPA-M or -N, the N-terminal portion of GPA-Mg is not glycosylated. Therefore, the multipin peptide synthesis was used for testing the specificity of the cross-reacting MoAbs. Among several anti- M and anti-N MoAbs tested, only three anti-M (E3, E6, 425/2B) agglutinated Mg erythrocytes and showed binding to the synthetic octapeptides corresponding to N-terminal sequences of GPA-M (SSTTGVAM), GPA-N (LSTTEVAM), and GPA-Mg (LSTNEVAM). Testing multiple peptide analogs (window and replacement analysis) showed that these MoAbs were specific for peptidic epitope in which Met8 and Val6 were the most essential amino acid residues. The amino acid replacements Ser<-->Leu1 or Gly<-->Glu5 (M v N) and Thr<-->Asn4 (M and N v Mg) had no or negligible effect on the reaction of synthetic peptides with the MoAbs. However, when Ser2, Thr3, and Thr4 carry O-linked sialooligosaccharides (normal GPA-M or -N), the MoAbs recognize Gly5- and sialic acid- dependent blood group M-related epitope. An interesting finding concerning anti-M/Mg MoAbs described here is the fact that glycosylation of amino acid residues adjacent to the most important part of peptidic epitope not only differentially modulates the proper exposure of peptidic epitope, but also alters the requirement for some amino acid residues present within the epitope. Pathologic conditions, including hematologic disorders, are often accompanied by alterations in protein glycosylation, resulting not only from differences in the structure of antigen polypeptide chain, but also from changes in specificity or expression of enzymes involved in glycosylation. Our present findings draw attention to possibility of the bidirectional modulation of protein antigenicity by glycosylation and may be helpful in interpretation of some results obtained with MoAb used for diagnostic or other purposes.

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