Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity

• Main Authors: Siti Naqiah Amrun, Lee, Cheryl Yi-Pin, Lee, Bernett, Fong, Siew-Wai, Young, Barnaby Edward, Chee, Rhonda Sin-Ling, Yeo, Nicholas Kim-Wah, Torres-Ruesta, Anthony, Carissimo, Guillaume, Poh, Chek Meng, Chang, Zi Wei, Tay, Matthew Zirui, Chan, Yi-Hao, Chen, Mark I-Cheng, Low, Jenny Guek-Hong, Tambyah, Paul A., Kalimuddin, Shirin, Pada, Surinder, Tan, Seow-Yen, Sun, Louisa Jin, Leo, Yee-Sin, Lye, David C., Renia, Laurent, Ng, Lisa F. P.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Medicine; Epitopes; SARS-CoV-2
• Online Access: https://hdl.handle.net/10356/145439
• Institution: Nanyang Technological University

Background: Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Methods: Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 13 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors. Findings: Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity. Interpretation: IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs).