tetano
Editor, Senior Moderator
Mol Immunol
. 2022 Nov 3;152:215-223.
doi: 10.1016/j.molimm.2022.10.016. Online ahead of print.
Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients
Ling Wang[SUP] 1 [/SUP], Juan Zhao[SUP] 2 [/SUP], Madison Schank[SUP] 2 [/SUP], Sushant Khanal[SUP] 2 [/SUP], Xindi Dang[SUP] 2 [/SUP], Dechao Cao[SUP] 2 [/SUP], Lam N T Nguyen[SUP] 2 [/SUP], Yi Zhang[SUP] 3 [/SUP], Xiao Y Wu[SUP] 2 [/SUP], James L Adkins[SUP] 3 [/SUP], Justin Brueggeman[SUP] 3 [/SUP], Jinyu Zhang[SUP] 2 [/SUP], Shunbin Ning[SUP] 2 [/SUP], Mohamed El Gazzar[SUP] 2 [/SUP], Jonathan P Moorman[SUP] 4 [/SUP], Zhi Q Yao[SUP] 5 [/SUP]
Affiliations
Abstract
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.
Keywords: B-cell epitopes; COVID-19; Convalescent plasma; Neutralizing antibodies; SARS-CoV-2.
. 2022 Nov 3;152:215-223.
doi: 10.1016/j.molimm.2022.10.016. Online ahead of print.
Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients
Ling Wang[SUP] 1 [/SUP], Juan Zhao[SUP] 2 [/SUP], Madison Schank[SUP] 2 [/SUP], Sushant Khanal[SUP] 2 [/SUP], Xindi Dang[SUP] 2 [/SUP], Dechao Cao[SUP] 2 [/SUP], Lam N T Nguyen[SUP] 2 [/SUP], Yi Zhang[SUP] 3 [/SUP], Xiao Y Wu[SUP] 2 [/SUP], James L Adkins[SUP] 3 [/SUP], Justin Brueggeman[SUP] 3 [/SUP], Jinyu Zhang[SUP] 2 [/SUP], Shunbin Ning[SUP] 2 [/SUP], Mohamed El Gazzar[SUP] 2 [/SUP], Jonathan P Moorman[SUP] 4 [/SUP], Zhi Q Yao[SUP] 5 [/SUP]
Affiliations
- PMID: 36379129
- PMCID: PMC9630139
- DOI: 10.1016/j.molimm.2022.10.016
Abstract
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.
Keywords: B-cell epitopes; COVID-19; Convalescent plasma; Neutralizing antibodies; SARS-CoV-2.