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

• Published in: Molecular immunology Vol. 152; pp. 215 - 223
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2022; Pergamon Press
• Subjects: Antibodies, Neutralizing; Antibodies, Viral; B-cell epitopes; Convalescent plasma; COVID-19; COVID-19 - therapy; COVID-19 Serotherapy; Epitopes, B-Lymphocyte; Humans; Leukocytes, Mononuclear; Neutralizing antibodies; SARS-CoV-2; Spike Glycoprotein, Coronavirus; B-cell epitopes; COVID-19; SARS-CoV-2; Convalescent plasma; Neutralizing antibodies
• ISSN: 0161-5890; 1872-9142; 1872-9142
• DOI: 10.1016/j.molimm.2022.10.016

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. •SARS-CoV-2-specific B cell epitopes are identified using COVID-19 convalescent plasma•The identified B-cell epitopes can elicit neutralizing antibodies, with titers declining significantly within 2–3 months.•The COVID-19 vaccine boosters may be necessary to sustain immunity in recovered patients and vaccinated individuals