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Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients

Identification of immunologic epitopes against SARS-CoV-2 is crucial for the discovery of diagnostic, therapeutic, and preventive targets. In this study, we used a pan-coronavirus peptide microarray to screen for potential B-cell epitopes and validated the results with peptide-based ELISA. Specifica...

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Autores principales: Wang, Ling, Zhao, Juan, Schank, Madison, Khanal, Sushant, Dang, Xindi, Cao, Dechao, Nguyen, Lam N.T., Zhang, Yi, Wu, Xiao Y., Adkins, James L., Brueggeman, Justin, Zhang, Jinyu, Ning, Shunbin, El Gazzar, Mohamed, Moorman, Jonathan P., Yao, Zhi Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pergamon Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630139/
https://www.ncbi.nlm.nih.gov/pubmed/36379129
http://dx.doi.org/10.1016/j.molimm.2022.10.016
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author Wang, Ling
Zhao, Juan
Schank, Madison
Khanal, Sushant
Dang, Xindi
Cao, Dechao
Nguyen, Lam N.T.
Zhang, Yi
Wu, Xiao Y.
Adkins, James L.
Brueggeman, Justin
Zhang, Jinyu
Ning, Shunbin
El Gazzar, Mohamed
Moorman, Jonathan P.
Yao, Zhi Q.
author_facet Wang, Ling
Zhao, Juan
Schank, Madison
Khanal, Sushant
Dang, Xindi
Cao, Dechao
Nguyen, Lam N.T.
Zhang, Yi
Wu, Xiao Y.
Adkins, James L.
Brueggeman, Justin
Zhang, Jinyu
Ning, Shunbin
El Gazzar, Mohamed
Moorman, Jonathan P.
Yao, Zhi Q.
author_sort Wang, Ling
collection PubMed
description Identification of immunologic epitopes against SARS-CoV-2 is crucial for the discovery of diagnostic, therapeutic, and preventive targets. In this study, we used a pan-coronavirus peptide microarray to screen for potential B-cell epitopes and validated the results with peptide-based ELISA. Specifically, we identified three linear B-cell epitopes on the SARS-CoV-2 proteome, which were recognized by convalescent plasma from COVID-19 patients. Interestingly, two epitopes (S 809–823 and R1ab 909–923) strongly reacted to convalescent plasma collected at the early phase (< 90 days) of COVID-19 symptom onset, whereas one epitope (M 5–19) reacted to convalescent plasma collected > 90 days after COVID-19 symptom onset. Neutralization assays using antibody depletion with the identified spike (S) peptides revealed that three S epitopes (S 557–571, S 789–803, and S 809–823) elicited neutralizing antibodies in COVID-19 patients. However, the levels of virus-specific antibody targeting S 789–803 only positively correlated with the neutralizing rates at the early phase (<60 days) after disease onset, and the antibody titers diminished quickly with no correlation to the neutralizing activity beyond two months after recovery from COVID-19. Importantly, stimulation of peripheral blood mononuclear cells from COVID-19-recovered patients with these SARS-CoV-2 S peptides resulted in poor virus-specific B cell activation, proliferation, differentiation into memory B cells, and production of immunoglobulin G (IgG) antibodies, despite the B-cells being functionally competent as demonstrated by their response to non-specific stimulation. Taken together, these findings indicate that these newly identified SARS-CoV-2-specific B-cell epitopes can elicit neutralizing antibodies, with titers and/or neutralizing activities declining significantly within 2–3 months in the convalescent plasma of COVID-19 patients.
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spelling pubmed-96301392022-11-03 Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients Wang, Ling Zhao, Juan Schank, Madison Khanal, Sushant Dang, Xindi Cao, Dechao Nguyen, Lam N.T. Zhang, Yi Wu, Xiao Y. Adkins, James L. Brueggeman, Justin Zhang, Jinyu Ning, Shunbin El Gazzar, Mohamed Moorman, Jonathan P. Yao, Zhi Q. Mol Immunol Article Identification of immunologic epitopes against SARS-CoV-2 is crucial for the discovery of diagnostic, therapeutic, and preventive targets. In this study, we used a pan-coronavirus peptide microarray to screen for potential B-cell epitopes and validated the results with peptide-based ELISA. Specifically, we identified three linear B-cell epitopes on the SARS-CoV-2 proteome, which were recognized by convalescent plasma from COVID-19 patients. Interestingly, two epitopes (S 809–823 and R1ab 909–923) strongly reacted to convalescent plasma collected at the early phase (< 90 days) of COVID-19 symptom onset, whereas one epitope (M 5–19) reacted to convalescent plasma collected > 90 days after COVID-19 symptom onset. Neutralization assays using antibody depletion with the identified spike (S) peptides revealed that three S epitopes (S 557–571, S 789–803, and S 809–823) elicited neutralizing antibodies in COVID-19 patients. However, the levels of virus-specific antibody targeting S 789–803 only positively correlated with the neutralizing rates at the early phase (<60 days) after disease onset, and the antibody titers diminished quickly with no correlation to the neutralizing activity beyond two months after recovery from COVID-19. Importantly, stimulation of peripheral blood mononuclear cells from COVID-19-recovered patients with these SARS-CoV-2 S peptides resulted in poor virus-specific B cell activation, proliferation, differentiation into memory B cells, and production of immunoglobulin G (IgG) antibodies, despite the B-cells being functionally competent as demonstrated by their response to non-specific stimulation. Taken together, these findings indicate that these newly identified SARS-CoV-2-specific B-cell epitopes can elicit neutralizing antibodies, with titers and/or neutralizing activities declining significantly within 2–3 months in the convalescent plasma of COVID-19 patients. Pergamon Press 2022-12 2022-11-03 /pmc/articles/PMC9630139/ /pubmed/36379129 http://dx.doi.org/10.1016/j.molimm.2022.10.016 Text en Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Wang, Ling
Zhao, Juan
Schank, Madison
Khanal, Sushant
Dang, Xindi
Cao, Dechao
Nguyen, Lam N.T.
Zhang, Yi
Wu, Xiao Y.
Adkins, James L.
Brueggeman, Justin
Zhang, Jinyu
Ning, Shunbin
El Gazzar, Mohamed
Moorman, Jonathan P.
Yao, Zhi Q.
Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients
title Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients
title_full Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients
title_fullStr Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients
title_full_unstemmed Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients
title_short Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients
title_sort identification of virus-specific b-cell epitopes by convalescent plasma from covid-19 patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630139/
https://www.ncbi.nlm.nih.gov/pubmed/36379129
http://dx.doi.org/10.1016/j.molimm.2022.10.016
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