A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein

Frontiers in Immunology

Immunology

Alma Fulurija¹  Magnus Gisslén²  Lars-Magnus Andersson²  Björn Andersson³  Sravya S. Nakka³  Hanna Kann³  Samuel B. Lundin⁴  Ali M. Harandi⁵ 

[1] Biotome Pty Ltd, Perth, WA, Australia;Biotome AB, Kullavik, Sweden;School of Biomedical Sciences, Marshall Centre, University of Western Australia, Perth, WA, Australia;Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden;Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;Biotome Pty Ltd, Perth, WA, Australia;Biotome AB, Kullavik, Sweden;Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden;Vaccine Evaluation Center, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada;

关键词: SARS-CoV-2;    B-cell epitope;    precision serology;    Spike protein;    cross-reactivity;   

DOI  :  10.3389/fimmu.2023.1166924

 received in 2023-02-15, accepted in 2023-04-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens.MethodsWe herein report mapping of linear IgG and IgA antibody epitopes of the SARS-CoV-2 Spike (S) protein in samples from SARS-CoV-2 exposed individuals along with certified SARS-CoV-2 verification plasma samples using peptide arrays.ResultsWe identified 21 distinct linear epitopes. Importantly, we showed that pre-pandemic serum samples contain IgG antibodies reacting to the majority of protein S epitopes, most likely as a result of prior infection with seasonal coronaviruses. Only 4 of the identified SARS-CoV-2 protein S linear epitopes were specific for SARS-CoV-2 infection. These epitopes are located at positions 278-298 and 550-586, just proximal and distal to the RBD, as well as at position 1134-1156 in the HR2 subdomain and at 1248-1271 in the C-terminal subdomain of protein S. To substantiate the applicability of our findings, we tested three of the high-accuracy protein S epitopes in a Luminex assay, using a certified validation plasma sample set from SARS-CoV-2 infected individuals. The Luminex results were well aligned with the peptide array results, and correlated very well with in-house and commercial immune assays for RBD, S1 and S1/S2 domains of protein S.ConclusionWe present a comprehensive mapping of linear B-cell epitopes of SARS-CoV-2 protein S, that identifies peptides suitable for a precision serology assay devoid of cross-reactivity. These results have implications for development of highly specific serology test for exposure to SARS-CoV-2 and other members of the coronaviridae family, as well as for rapid development of serology tests for future emerging pandemic threats.

【 授权许可】

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Copyright © 2023 Lundin, Kann, Fulurija, Andersson, Nakka, Andersson, Gisslén and Harandi