Systematic Bioinformatic Approach for Prediction of Linear B-Cell Epitopes on Dengue E and prM Protein

B-cell epitopes on the envelope (E) and premembrane (prM) proteins of dengue virus (DENV) were predicted using bioinformatics tools, BepiPred, Ellipro, and SVMTriP. Predicted epitopes, 32 and 17 for E and prM proteins, respectively, were then characterized for their level of conservations. The epitopes, EP4/E (48–55), epitope number 4 of E protein at amino acids 48–55, EP9/E (165–182), EP11/E (218–233), EP20/E (322–349), EP21/E (326–353), EP23/E (356–365), and EP25/E (380–386), showed a high intraserotype conservancy with very low pan-serotype conservancy, demonstrating a potential target as serotype specific diagnostic markers. EP3 (30–41) located in domain-I and EP26/E (393–409), EP27/E (416–435), EP28/E (417–430) located in the stem region of E protein, and EP8/prM (93–112) from the prM protein have a pan-serotype conservancy higher than 70%. These epitopes indicate a potential use as universal vaccine candidates, subjected to verification of their potential in viral neutralization. EP2/E (16–21), EP5/E (62–123), EP6/E (63–89), EP19/E (310–329), and EP24/E (371–402), which have more than 50% pan-serotype conservancies, were found on E protein regions that are important in host cell attachment. Previous studies further show evidence for some of these epitopes to generate cross-reactive neutralizing antibodies, indicating their importance in antiviral strategies for DENV. This study suggests that bioinformatic approaches are attractive first line of screening for identification of linear B-cell epitopes.

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Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

10.1101/2020.12.13.422550 ◽

2020 ◽

Author(s):

Lin Li ◽

Zhongpeng Zhao ◽

Xiaolan Yang ◽

WenDong Li ◽

Shaolong Chen ◽

...

Keyword(s):

B Cell ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Cell Epitope ◽

Effective Vaccine ◽

B Cell Epitopes ◽

S Protein ◽

The Public ◽

B Cell Epitope ◽

Linear B

SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with serum antibodies from horse, mouse, and monkey inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

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

10.1101/639542 ◽

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.

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Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodiesIdentification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

10.21203/rs.3.rs-348597/v1 ◽

2021 ◽

Author(s):

Lin Li ◽

Zhongpeng Zhao ◽

Xiaolan Yang ◽

Wendong Li ◽

Shaolong Chen ◽

...

Keyword(s):

B Cell ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Cell Epitope ◽

Spike Protein ◽

Effective Vaccine ◽

B Cell Epitopes ◽

S Protein ◽

B Cell Epitope ◽

Linear B

Abstract SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with pooled serum antibodies from horses, mice, and monkeys inoculated with different SARS-CoV-2 vaccine candidates or five patients recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

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BCEPS: A Web Server to Predict Linear B Cell Epitopes with Enhanced Immunogenicity and Cross-Reactivity

Cells ◽

10.3390/cells10102744 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2744

Author(s):

Alvaro Ras-Carmona ◽

Hector F. Pelaez-Prestel ◽

Esther M. Lafuente ◽

Pedro A. Reche

Keyword(s):

B Cell ◽

Neutralizing Antibodies ◽

Protein Structures ◽

Web Server ◽

Cross Reactivity ◽

Support Vector ◽

B Cell Epitopes ◽

Antibody Recognition ◽

Mhc Ii ◽

Linear B

Prediction of linear B cell epitopes is of interest for the production of antigen-specific antibodies and the design of peptide-based vaccines. Here, we present BCEPS, a web server for predicting linear B cell epitopes tailored to select epitopes that are immunogenic and capable of inducing cross-reactive antibodies with native antigens. BCEPS implements various machine learning models trained on a dataset including 555 linearized conformational B cell epitopes that were mined from antibody–antigen protein structures. The best performing model, based on a support vector machine, reached an accuracy of 75.38% ± 5.02. In an independent dataset consisting of B cell epitopes retrieved from the Immune Epitope Database (IEDB), this model achieved an accuracy of 67.05%. In BCEPS, predicted epitopes can be ranked according to properties such as flexibility, accessibility and hydrophilicity, and with regard to immunogenicity, as judged by their predicted presentation by MHC II molecules. BCEPS also detects if predicted epitopes are located in ectodomains of membrane proteins and if they possess N-glycosylation sites hindering antibody recognition. Finally, we exemplified the use of BCEPS in the SARS-CoV-2 Spike protein, showing that it can identify B cell epitopes targeted by neutralizing antibodies.

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Linear B-Cell Epitopes in Human Norovirus GII.4 Capsid Protein Elicit Blockade Antibodies

Vaccines ◽

10.3390/vaccines9010052 ◽

2021 ◽

Vol 9 (1) ◽

pp. 52

Author(s):

Hassan Moeini ◽

Suliman Qadir Afridi ◽

Sainitin Donakonda ◽

Percy A. Knolle ◽

Ulrike Protzer ◽

...

Keyword(s):

B Cell ◽

Capsid Protein ◽

Immune Escape ◽

Solvent Accessibility ◽

Effective Vaccine ◽

Blood Group Antigens ◽

Human Norovirus ◽

B Cell Epitopes ◽

Blocking Rate ◽

Linear B

Human norovirus (HuNoV) is the leading cause of nonbacterial gastroenteritis worldwide with the GII.4 genotype accounting for over 80% of infections. The major capsid protein of GII.4 variants is evolving rapidly, resulting in new epidemic variants with altered antigenic potentials that must be considered for the development of an effective vaccine. In this study, we identify and characterize linear blockade B-cell epitopes in HuNoV GII.4. Five unique linear B-cell epitopes, namely P2A, P2B, P2C, P2D, and P2E, were predicted on the surface-exposed regions of the capsid protein. Evolving of the surface-exposed epitopes over time was found to correlate with the emergence of new GII.4 outbreak variants. Molecular dynamic simulation (MD) analysis and molecular docking revealed that amino acid substitutions in the putative epitopes P2B, P2C, and P2D could be associated with immune escape and the appearance of new GII.4 variants by affecting solvent accessibility and flexibility of the antigenic sites and histo-blood group antigens (HBAG) binding. Testing the synthetic peptides in wild-type mice, epitopes P2B (336–355), P2C (367–384), and P2D (390–400) were recognized as GII.4-specific linear blockade epitopes with the blocking rate of 68, 55 and 28%, respectively. Blocking rate was found to increase to 80% using the pooled serum of epitopes P2B and P2C. These data provide a strategy for expanding the broad blockade potential of vaccines for prevention of NoV infection.

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Mining of linear B cell epitopes of SARS-CoV-2 ORF8 protein from COVID-19 patients

Emerging Microbes & Infections ◽

10.1080/22221751.2021.1931465 ◽

2021 ◽

pp. 1-19

Author(s):

Xiaohui Wang ◽

Joy-Yan Lam ◽

Linlei Chen ◽

Shannon Wing-Ngor Au ◽

Kelvin K. W. To ◽

...

Keyword(s):

B Cell ◽

B Cell Epitopes ◽

Linear B

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Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection

PLoS ONE ◽

10.1371/journal.pone.0149638 ◽

2016 ◽

Vol 11 (2) ◽

pp. e0149638 ◽

Cited By ~ 11

Author(s):

Hui-Jie Yang ◽

Jin-Yong Zhang ◽

Chao Wei ◽

Liu-Yang Yang ◽

Qian-Fei Zuo ◽

...

Keyword(s):

Staphylococcus Aureus ◽

B Cell ◽

Protein C ◽

Transport Protein ◽

B Cell Epitopes ◽

Aureus Infection ◽

Manganese Transport ◽

Linear B

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Anaplasma marginale Major Surface Protein 2 CD4+-T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR

Infection and Immunity ◽

10.1128/iai.72.12.7360-7366.2004 ◽

2004 ◽

Vol 72 (12) ◽

pp. 7360-7366 ◽

Cited By ~ 35

Author(s):

Jeffrey R. Abbott ◽

Guy H. Palmer ◽

Chris J. Howard ◽

Jayne C. Hope ◽

Wendy C. Brown

Keyword(s):

T Cell ◽

B Cell ◽

Surface Protein ◽

Anaplasma Marginale ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

Major Surface Protein ◽

Hypervariable Regions ◽

Major Surface ◽

Linear B

ABSTRACT Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4+ T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.

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