Epitope-specific antibody responses differentiate COVID-19 outcomes and variants of concern

Authors

Courtney Voss, Schulich School of Medicine & Dentistry
Sally Esmail, Schulich School of Medicine & Dentistry
Xuguang Liu, Schulich School of Medicine & Dentistry
Michael J. Knauer, Schulich School of Medicine & Dentistry
Suzanne Ackloo, University of Toronto
Tomonori Kaneko, Schulich School of Medicine & Dentistry
Lori Lowes, Schulich School of Medicine & Dentistry
Peter Stogios, University of Toronto
Almagul Seitova, University of Toronto
Ashley Hutchinson, University of Toronto
Farhad Yusifov, University of Toronto
Tatiana Skarina, University of Toronto
Elena Evdokimova, University of Toronto
Peter Loppnau, University of Toronto
Pegah Ghiabi, University of Toronto
Taraneh Haijan, University of Toronto
Shanshan Zhong, Schulich School of Medicine & Dentistry
Husam Abdoh, Schulich School of Medicine & Dentistry
Benjamin D. Hedley, Schulich School of Medicine & Dentistry
Vipin Bhayana, Schulich School of Medicine & Dentistry
Claudio M. Martin, Western University
Marat Slessarev, Western University
Benjamin Chin-Yee, Schulich School of Medicine & Dentistry
Douglas D. Fraser, Western UniversityFollow
Ian Chin-Yee, Schulich School of Medicine & Dentistry
Shawn S.C. Li, Schulich School of Medicine & Dentistry

Document Type

Article

Publication Date

7-8-2021

Journal

JCI Insight

Volume

6

Issue

13

URL with Digital Object Identifier

10.1172/jci.insight.148855

Abstract

BACKGROUND. The role of humoral immunity in 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 linear epitopes from the spike (S) and nucleocapsid (N) proteins and showed that the epitopes enabled higher resolution antibody profiling than the S or N protein antigen. 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 of concern B.1.1.7 altered the specificity of the corresponding epitopes. CONCLUSION. Epitope-resolved antibody testing not only affords 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, but it also may potentially be used to predict clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants of concern in both the peptide array and latex agglutination formats. FUNDING. Ontario Research Fund (ORF) COVID-19 Rapid Research Fund, Toronto COVID-19 Action Fund, Western University, Lawson Health Research Institute, London Health Sciences Foundation, and Academic Medical Organization of Southwestern Ontario (AMOSO) Innovation Fund.