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 ◽  
...  

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.

2020 ◽  
Author(s):  
Lin Li ◽  
Zhongpeng Zhao ◽  
Xiaolan Yang ◽  
WenDong Li ◽  
Shaolong Chen ◽  
...  

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.


2021 ◽  
Author(s):  
Lin Li ◽  
Zhongpeng Zhao ◽  
Xiaolan Yang ◽  
Wendong Li ◽  
Shaolong Chen ◽  
...  

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kanokporn Polyiam ◽  
Waranyoo Phoolcharoen ◽  
Namphueng Butkhot ◽  
Chanya Srisaowakarn ◽  
Arunee Thitithanyanont ◽  
...  

AbstractSARS-CoV-2 continues to infect an ever-expanding number of people, resulting in an increase in the number of deaths globally. With the emergence of new variants, there is a corresponding decrease in the currently available vaccine efficacy, highlighting the need for greater insights into the viral epitope profile for both vaccine design and assessment. In this study, three immunodominant linear B cell epitopes in the SARS-CoV-2 spike receptor-binding domain (RBD) were identified by immunoinformatics prediction, and confirmed by ELISA with sera from Macaca fascicularis vaccinated with a SARS-CoV-2 RBD subunit vaccine. Further immunoinformatics analyses of these three epitopes gave rise to a method of linear B cell epitope prediction and selection. B cell epitopes in the spike (S), membrane (M), and envelope (E) proteins were subsequently predicted and confirmed using convalescent sera from COVID-19 infected patients. Immunodominant epitopes were identified in three regions of the S2 domain, one region at the S1/S2 cleavage site and one region at the C-terminus of the M protein. Epitope mapping revealed that most of the amino acid changes found in variants of concern are located within B cell epitopes in the NTD, RBD, and S1/S2 cleavage site. This work provides insights into B cell epitopes of SARS-CoV-2 as well as immunoinformatics methods for B cell epitope prediction, which will improve and enhance SARS-CoV-2 vaccine development against emergent variants.


2006 ◽  
Vol 13 (2-4) ◽  
pp. 125-132 ◽  
Author(s):  
L. Guilherme ◽  
K. C. Faé ◽  
F. Higa ◽  
L. Chaves ◽  
S. E. Oshiro ◽  
...  

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.


2019 ◽  
Vol 14 (3) ◽  
pp. 226-233 ◽  
Author(s):  
Cangzhi Jia ◽  
Hongyan Gong ◽  
Yan Zhu ◽  
Yixia Shi

Background: B-cell epitope prediction is an essential tool for a variety of immunological studies. For identifying such epitopes, several computational predictors have been proposed in the past 10 years. Objective: In this review, we summarized the representative computational approaches developed for the identification of linear B-cell epitopes. </P><P> Methods: We mainly discuss the datasets, feature extraction methods and classification methods used in the previous work. Results: The performance of the existing methods was not very satisfying, and so more effective approaches should be proposed by considering the structural information of proteins. Conclusion: We consider existing challenges and future perspectives for developing reliable methods for predicting linear B-cell epitopes.


2019 ◽  
Vol 8 (7) ◽  
Author(s):  
Siti Naqiah Amrun ◽  
Wearn‐Xin Yee ◽  
Farhana Abu Bakar ◽  
Bernett Lee ◽  
Yiu‐Wing Kam ◽  
...  

2018 ◽  
Vol 9 ◽  
Author(s):  
Monique Paiva Campos ◽  
Fabiano Borges Figueiredo ◽  
Fernanda Nazaré Morgado ◽  
Alinne Rangel dos Santos Renzetti ◽  
Sara Maria Marques de Souza ◽  
...  

2020 ◽  
Vol 9 (2) ◽  
Author(s):  
Siti Naqiah Amrun ◽  
Wearn‐Xin Yee ◽  
Farhana Abu Bakar ◽  
Bernett Lee ◽  
Yiu‐Wing Kam ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Mahesha N. Nadugala ◽  
Prasad H. Premaratne ◽  
Charitha L. Goonasekara

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.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2744
Author(s):  
Alvaro Ras-Carmona ◽  
Hector F. Pelaez-Prestel ◽  
Esther M. Lafuente ◽  
Pedro A. Reche

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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