scholarly journals The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes

2020 ◽  
Author(s):  
Xianlin Yuan ◽  
liangping li
Keyword(s):  
B Cell ◽  
Large Scale ◽  
Population Change ◽  
Vaccine Development ◽  
Rna Virus ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Common Variants ◽  
B Cell Epitopes ◽  
S Protein

AbstractSARS-CoV-2 has rapidly transmitted worldwide and results in the COVID-19 pandemic. Spike glycoprotein on surface is a key factor of viral transmission, and has appeared a lot of variants due to gene mutations, which may influence the viral antigenicity and vaccine efficacy. Here, we used bioinformatic tools to analyze B-cell epitopes of prototype S protein and its 9 common variants. 12 potential linear and 53 discontinuous epitopes of B-cells were predicted from the S protein prototype. Importantly, by comparing the epitope alterations between prototype and variants, we demonstrate that B-cell epitopes and antigenicity of 9 variants appear significantly different alterations. The dominant D614G variant impacts the potential epitope least, only with moderately elevated antigenicity, while the epitopes and antigenicity of some mutants(V483A, V367F, etc.) with small incidence in the population change greatly. These results suggest that the currently developed vaccines should be valid for a majority of SARS-CoV-2 infectors. This study provides a scientific basis for large-scale application of SARS-CoV-2 vaccines and for taking precautions against the probable appearance of antigen escape induced by genetic variation after vaccination.Author SummaryThe global pandemic of SARS-CoV-2 has lasted for more than half a year and has not yet been contained. Until now there is no effective treatment for SARS-CoV-2 caused disease (COVID-19). Successful vaccine development seems to be the only hope. However, this novel coronavirus belongs to the RNA virus, there is a high mutation rate in the genome, and these mutations often locate on the Spike proteins of virus, the gripper of the virus entering the cells. Vaccination induce the generation of antibodies, which block Spike protein. However, the Spike protein variants may change the recognition and binding of antibodies and make the vaccine ineffective. In this study, we predict neutralizing antibody recognition sites (B cell epitopes) of the prototype S protein of SARS-COV2, along with several common variants using bioinformatics tools. We discovered the variability in antigenicity among the mutants, for instance, in the more widespread D614G variant the change of epitope was least affected, only with slight increase of antigenicity. However, the antigenic epitopes of some mutants change greatly. These results could be of potential importance for future vaccine design and application against SARS-CoV2 variants.

scholarly journals 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

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.

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

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.

scholarly journals SARS-CoV-2-induced humoral immunity through B cell epitope analysis and neutralizing activity in COVID-19 infected individuals in Japan

2020 ◽  
Author(s):  
Shota Yoshida ◽  
Chikako Ono ◽  
Hiroki Hayashi ◽  
Satoshi Shiraishi ◽  
Kazunori Tomono ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Production ◽  
Vaccine Development ◽  
Hot Spot ◽  
Cell Epitope ◽  
Large Individual ◽  
B Cell Epitopes ◽  
S Protein ◽  
Neutralizing Activity ◽  
B Cell Epitope

AbstractThe aim of this study is to understand adaptive immunity to SARS-CoV-2 through the analysis of B cell epitope and neutralizing activity in coronavirus disease 2019 (COVID-19) patients. We obtained serum from thirteen COVID-19 patients. Most individuals revealed neutralizing activity against SARS-CoV-2 assessed by a pseudotype virus-neutralizing assay. The antibody production against the spike glycoprotein (S protein) or receptor-binding domain (RBD) of SARS-CoV-2 was elevated, with large individual differences, as assessed by ELISA. In the analysis of the predicted the linear B cell epitopes, two regions (671-690 aa. and 1146-1164 aa.), which were located in S1 and S2 but not in the RBD, were highly reactive with the sera from patients. In the further analysis of the B cell epitope within the S protein by utilizing a B cell epitope array, a hot spot in the N-terminal domain of the S protein but not the RBD was observed in individuals with neutralizing activity. Overall, the analysis of antibody production and B cell epitopes of the S protein from patient serum may provide a novel target for the vaccine development against SARS-CoV-2.

scholarly journals Bioinformatic analysis of epitope-based vaccine design against the novel SARS-COV-2

2020 ◽  
Author(s):  
Hongzhi Chen ◽  
Xiang Wu
Keyword(s):  
B Cell ◽  
Nucleocapsid Protein ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Cell Epitope ◽  
Bioinformatic Analysis ◽  
Spike Protein ◽  
B Cell Epitopes ◽  
Surface Accessibility ◽  
Binding Peptides

Abstract Background: An outbreak of infection caused by SARS-COV-2 recently has brought great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of an impending pandemic. This study aimed to predict the protective epitopes with bioinformatic methods and resources for vaccine development. Methods: ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DISCTOPE server. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forcasted epitopes were characterized for immunogen potential evaluation.Results: A total of 63 sequential B-cell epitopes on spike protein were predicted and 3 peptides (333-338, 648-663, 1064-1079) exhibited high antigenicity score and good surface accessibility in our modeling. 8 residues within spike protein (Gly184, Gly502, Lys558, Pro561, Pro809, Ser810, Lys811, Pro812) are forcasted as components of discontinuous B-cell epitopes. The bioinformatic analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind class-I and class-II molecule respectively. The peptide (104-112) has a high immunogenicity score and was predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions: Linear B-cell epitopes (333-338, 648-663, 1064-1079) and discontinuous B-cell epitopes (Gly184, Gly502, Lys558, Pro561, Pro809, Ser810, Lys811, Pro812) on spike protein, T-cell epitope (104-112) within nucleocapsid protein were identified and recommended for developing vaccine against SARS-COV-2.

scholarly journals Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2

2020 ◽  
Author(s):  
Hongzhi Chen ◽  
Lingli Tang ◽  
Xinling Yu ◽  
Jie Zhou ◽  
Yunfeng Chang ◽  
...  
Keyword(s):  
B Cell ◽  
Nucleocapsid Protein ◽  
Bioinformatics Analysis ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Cell Epitope ◽  
Spike Protein ◽  
B Cell Epitopes ◽  
Surface Accessibility ◽  
Binding Peptides

Abstract Background: An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. Methods: ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. Results: A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike315-324, Spike333-338, Spike648-663, Spike1064-1079) exhibited high antigenicity score and good surface accessibility. 10 residues within spike protein (Gly496, Glu498, Pro499, Thr500, Leu1141, Gln1142, Pro1143, Glu1144, Leu1145, Asp1146) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind class-I and class-II molecule respectively. The peptides (Nucleocapsid66-75, Nucleocapsid104-112) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions: B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.

scholarly journals Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2

2020 ◽  
Author(s):  
Hongzhi Chen ◽  
Lingli Tang ◽  
Xinling Yu ◽  
Jie Zhou ◽  
Yunfeng Chang ◽  
...  
Keyword(s):  
B Cell ◽  
Mhc Class Ii ◽  
Nucleocapsid Protein ◽  
Bioinformatics Analysis ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Spike Protein ◽  
B Cell Epitopes ◽  
Surface Accessibility ◽  
Binding Peptides

Abstract Background: An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. Methods : ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. Results : A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike 315-324 , Spike 333-338 , Spike 648-663 , Spike 1064-1079 ) exhibited high antigenicity score and good surface accessibility. 10 residues within spike protein (Gly 496 , Glu 498 , Pro 499 , Thr 500 , Leu 1141 , Gln 1142 , Pro 1143 , Glu 1144 , Leu 1145 , Asp 1146 ) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind MHC class I and MHC class II molecule respectively. The peptides (Nucleocapsid 66-75 , Nucleocapsid 104-112 ) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions : B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.

scholarly journals Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Hong-Zhi Chen ◽  
Ling-Li Tang ◽  
Xin-Ling Yu ◽  
Jie Zhou ◽  
Yun-Feng Chang ◽  
...  
Keyword(s):  
B Cell ◽  
Mhc Class Ii ◽  
Nucleocapsid Protein ◽  
Bioinformatics Analysis ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Spike Protein ◽  
B Cell Epitopes ◽  
Surface Accessibility ◽  
Binding Peptides

Abstract Background An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. Methods The genome sequence and protein sequences of SARS-CoV-2 were retrieved from the National Center for Biotechnology Information (NCBI) database. ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. Results A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike315–324, Spike333–338, Spike648–663, Spike1064–1079) exhibited high antigenicity score and good surface accessibility. Ten residues within spike protein (Gly496, Glu498, Pro499, Thr500, Leu1141, Gln1142, Pro1143, Glu1144, Leu1145, Asp1146) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind MHC class I and MHC class II molecules respectively. The peptides (Nucleocapsid66–75, Nucleocapsid104–112) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.

scholarly journals Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2

2020 ◽  
Author(s):  
hongzhi chen ◽  
Lingli Tang ◽  
Xinling Yu ◽  
Jie Zhou ◽  
Yunfeng Chang ◽  
...  
Keyword(s):  
B Cell ◽  
Nucleocapsid Protein ◽  
Bioinformatics Analysis ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Cell Epitope ◽  
Spike Protein ◽  
B Cell Epitopes ◽  
Surface Accessibility ◽  
Binding Peptides

Abstract Background: An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. Methods : The genome sequence and protein sequences of SARS-CoV-2 were retrieved from the National Center for Biotechnology Information (NCBI) database. ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. Results : A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike 315-324 , Spike 333-338 , Spike 648-663 , Spike 1064-1079 ) exhibited high antigenicity score and good surface accessibility. Ten residues within spike protein (Gly 496 , Glu 498 , Pro 499 , Thr 500 , Leu 1141 , Gln 1142 , Pro 1143 , Glu 1144 , Leu 1145 , Asp 1146 ) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind MHC classⅠand MHC classⅡ molecules respectively. The peptides (Nucleocapsid 66-75 , Nucleocapsid 104-112 ) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions : B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.

scholarly journals SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikolaos C. Kyriakidis ◽  
Andrés López-Cortés ◽  
Eduardo Vásconez González ◽  
Alejandra Barreto Grimaldos ◽  
Esteban Ortiz Prado
Keyword(s):  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Development ◽  
Rna Virus ◽  
Protein S ◽  
Effective Vaccine ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Advantages And Disadvantages ◽  
The World

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

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