Epitope-resolved serology test differentiates the clinical outcome of COVID-19 and identifies defects in antibody response in SARS-CoV-2 variants

  1. Courtney Voss
  2. Sally Esmail
  3. Xuguang Liu
  4. Michael J. Knauer
  5. Suzanne Ackloo
  6. Tomonori Kaneko
  7. Lori Lowes
  8. Peter Stogios
  9. Almagul Seitova
  10. Ashley Hutchinson
  11. Farhad Yusifov
  12. Tatiana Skarina
  13. Elena Evdokimova
  14. Peter Loppnau
  15. Pegah Ghiabi
  16. Taraneh Haijian
  17. Shanshan Zhong
  18. Husam Abdoh
  19. Benjamin D. Hedley
  20. Vipin Bhayana
  21. Claudio M. Martin
  22. Marat Slessarev
  23. Benjamin Chin-Yee
  24. Douglas D. Fraser
  25. Ian Chin-Yee
  26. Shawn S-C. Li
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Abstract

BACKGROUND

The role of humoral immunity in the coronavirus disease 2019 (COVID-19) is not fully understood owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome.

METHODS

Using SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution.

RESULTS

We identified 54 linear epitopes from the Spike (S) and Nucleocapsid (N) protein and showed that epitopes enabled higher resolution antibody profiling than protein antigens. Specifically, we found that antibody responses to the S(811-825), S(881-895) and N(156-170) epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant B.1.1.7 altered the specificity of the corresponding epitopes.

CONCLUSIONS

Epitope-resolved antibody testing not only offers a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, it may also be used as predictor of clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants in both the peptide array and latex agglutination formats.

FUNDING

Ontario Research Fund (ORF)-COVID-19 Rapid Research Fund, the Toronto COVID-19 Action Fund, Western University, the Lawson Health Research Institute, the London Health Sciences Foundation, and the AMOSO Innovation Fund.

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