SARS-CoV-2 neutralizing antibody responses towards full-length spike protein and the receptor-binding domain
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Tools to monitor SARS-CoV-2 transmission and immune responses are needed. We present a neutralization ELISA to determine the levels of Ab-mediated virus neutralization and a preclinical model of focused immunization strategy. The ELISA is strongly correlated with the elaborate plaque reduction neutralization test (ρ = 0.9231, p < 0.0001). The neutralization potency of convalescent sera strongly correlates to IgG titers against SARS-CoV-2 receptor-binding domain (RBD) and spike (ρ = 0.8291 and 0.8297, respectively; p < 0.0001) and to a lesser extent with the IgG titers against protein N (ρ = 0.6471, p < 0.0001). The preclinical vaccine NMRI mice models using RBD and full-length spike Ag as immunogens show a profound Ab neutralization capacity (IC50 5 1.9 3 104 to 2.6 3 104 and 3.9 3 103 to 5.2 3 103, respectively). Using a panel of novel high-affinity murine mAbs, we also show that a majority of the RBD-raised mAbs have inhibitory properties, whereas only a few of the spike-raised mAbs do. The ELISA-based viral neutralization test offers a time- and cost-effective alternative to the plaque reduction neutralization test. The immunization results indicate that vaccine strategies focused only on the RBD region may have advantages compared with the full spike.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Immunology |
Vol/bind | 207 |
Udgave nummer | 3 |
Sider (fra-til) | 878-887 |
Antal sider | 10 |
ISSN | 0022-1767 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
This work was supported by grants from the Carlsberg Foundation (CF20-0045), the Novo Nordisk Foundation (NFF205A0063505 and NNF20SA0064201), and the Independent Research Fund Denmark (0214-00001B).
Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc. All rights reserved.
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