EBioMedicine (Aug 2020)
Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity
- Siti Naqiah Amrun,
- Cheryl Yi-Pin Lee,
- Bernett Lee,
- Siew-Wai Fong,
- Barnaby Edward Young,
- Rhonda Sin-Ling Chee,
- Nicholas Kim-Wah Yeo,
- Anthony Torres-Ruesta,
- Guillaume Carissimo,
- Chek Meng Poh,
- Zi Wei Chang,
- Matthew Zirui Tay,
- Yi-Hao Chan,
- Mark I-Cheng Chen,
- Jenny Guek-Hong Low,
- Paul A. Tambyah,
- Shirin Kalimuddin,
- Surinder Pada,
- Seow-Yen Tan,
- Louisa Jin Sun,
- Yee-Sin Leo,
- David C. Lye,
- Laurent Renia,
- Lisa F.P. Ng
Affiliations
- Siti Naqiah Amrun
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Cheryl Yi-Pin Lee
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Bernett Lee
- Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Siew-Wai Fong
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Department of Biological Sciences, National University of Singapore, Singapore, Singapore
- Barnaby Edward Young
- National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore
- Rhonda Sin-Ling Chee
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Nicholas Kim-Wah Yeo
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Anthony Torres-Ruesta
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Guillaume Carissimo
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Chek Meng Poh
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Zi Wei Chang
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Matthew Zirui Tay
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Yi-Hao Chan
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Mark I-Cheng Chen
- National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 12 Science Drive 2, Singapore 117549, Singapore
- Jenny Guek-Hong Low
- Department of Infectious Diseases, Singapore General Hospital, 31 Third Hospital Ave, Singapore 168753, Singapore; Emerging Infectious Disease Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
- Paul A. Tambyah
- National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore; Department of Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore
- Shirin Kalimuddin
- Department of Infectious Diseases, Singapore General Hospital, 31 Third Hospital Ave, Singapore 168753, Singapore; Emerging Infectious Disease Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
- Surinder Pada
- Division of Infectious Diseases, Ng Teng Fong Hospital, 1 Jurong East Street 21, Singapore 609606, Singapore
- Seow-Yen Tan
- Department of Infectious Diseases, Changi General Hospital, 2 Simei Street 3, Singapore 529889, Singapore
- Louisa Jin Sun
- Alexandra Hospital, 378 Alexandra Road, Singapore 159964, Singapore
- Yee-Sin Leo
- National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, 10 Medical Drive, Singapore 117597, Singapore
- David C. Lye
- National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, Singapore 308442, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, 10 Medical Drive, Singapore 117597, Singapore
- Laurent Renia
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore
- Lisa F.P. Ng
- Infectious Diseases Horizontal Technology Centre (ID HTC), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom; Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom; Corresponding author at: Laboratory of Microbial Immunity, Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos #04-06, Biopolis, Singapore 138648, Singapore.
- Journal volume & issue
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Vol. 58
p. 102911
Abstract
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). Funding: Biomedical Research Council (BMRC), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), and National Medical Research Council (NMRC) COVID-19 Research fund (COVID19RF-001) and CCGSFPOR20002. ATR is supported by the Singapore International Graduate Award (SINGA), A*STAR.