SARS-CoV-2 neutralizing antibody responses towards full-length spike protein and the receptor-binding domain
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SARS-CoV-2 neutralizing antibody responses towards full-length spike protein and the receptor-binding domain. / Bayarri-Olmos, Rafael; Idorn, Manja; Rosbjerg, Anne; Pérez-Alós, Laura; Hansen, Cecilie Bo; Johnsen, Laust Bruun; Helgstrand, Charlotte; Zosel, Franziska; Bjelke, Jais Rose; Öberg, Fredrik Kryh; Søgaard, Max; Paludan, Søren R.; Bak-Thomsen, Theresa; Jardine, Joseph G.; Skjoedt, Mikkel Ole; Garred, Peter.
In: Journal of Immunology, Vol. 207, No. 3, 2021, p. 878-887.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - SARS-CoV-2 neutralizing antibody responses towards full-length spike protein and the receptor-binding domain
AU - Bayarri-Olmos, Rafael
AU - Idorn, Manja
AU - Rosbjerg, Anne
AU - Pérez-Alós, Laura
AU - Hansen, Cecilie Bo
AU - Johnsen, Laust Bruun
AU - Helgstrand, Charlotte
AU - Zosel, Franziska
AU - Bjelke, Jais Rose
AU - Öberg, Fredrik Kryh
AU - Søgaard, Max
AU - Paludan, Søren R.
AU - Bak-Thomsen, Theresa
AU - Jardine, Joseph G.
AU - Skjoedt, Mikkel Ole
AU - Garred, Peter
N1 - Publisher Copyright: Copyright © 2021 by The American Association of Immunologists, Inc. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.4049/jimmunol.2100272
DO - 10.4049/jimmunol.2100272
M3 - Journal article
C2 - 34301847
AN - SCOPUS:85111666489
VL - 207
SP - 878
EP - 887
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -
ID: 301343081