The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum

Lu Lu; Allen Wing Ho Chu; Ricky Ruiqi Zhang; Wan Mui Chan; Jonathan Daniel Ip; Hoi Wah Tsoi; Lin lei Chen; Jian Piao Cai; David Christopher Lung; Anthony Raymond Tam; Yat Sun Yau; Mike Yat Wah Kwan; Wing Kin To; Owen Tak Yin Tsang; Larry Lap Yip Lee; Haisu Yi; Tak Chuen Ip; Rosana Wing Shan Poon; Gilman Kit Hang Siu; Bobo Wing Yee Mok; Vincent Chi Chung Cheng; Kwok Hung Chan; Kwok Yung Yuen; Ivan Fan Ngai Hung; Kelvin Kai Wang To

doi:10.1016/j.ebiom.2021.103544

The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum

Lu Lu, Allen Wing Ho Chu, Ricky Ruiqi Zhang, Wan Mui Chan, Jonathan Daniel Ip, Hoi Wah Tsoi, Lin lei Chen, Jian Piao Cai, David Christopher Lung, Anthony Raymond Tam, Yat Sun Yau, Mike Yat Wah Kwan, Wing Kin To, Owen Tak Yin Tsang, Larry Lap Yip Lee, Haisu Yi, Tak Chuen Ip, Rosana Wing Shan Poon, Gilman Kit Hang Siu, Bobo Wing Yee MokVincent Chi Chung Cheng, Kwok Hung Chan, Kwok Yung Yuen, Ivan Fan Ngai Hung, Kelvin Kai Wang To

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

Abstract

Background: Several SARS-CoV-2 lineages with spike receptor binding domain (RBD) N501Y mutation have spread globally. We evaluated the impact of N501Y on neutralizing activity of COVID-19 convalescent sera and on anti-RBD IgG assays. Methods: The susceptibility to neutralization by COVID-19 patients’ convalescent sera from Hong Kong were compared between two SARS-CoV-2 isolates (B117-1/B117-2) from the α variant with N501Y and 4 non-N501Y isolates. The effect of N501Y on antibody binding was assessed. The performance of commercially-available IgG assays was determined for patients infected with N501Y variants. Findings: The microneutralization antibody (MN) titers of convalescent sera from 9 recovered COVID-19 patients against B117-1 (geometric mean titer[GMT],80; 95% CI, 47–136) were similar to those against the non-N501Y viruses. However, MN titer of these serum against B117-2 (GMT, 20; 95% CI, 11–36) was statistically significantly reduced when compared with non-N501Y viruses (P < 0.01; one-way ANOVA). The difference between B117-1 and B117-2 was confirmed by testing 60 additional convalescent sera. B117-1 and B117-2 differ by only 3 amino acids (nsp2-S512Y, nsp13-K460R, spike-A1056V). Enzyme immunoassay using 272 convalescent sera showed reduced binding of anti-RBD IgG to N501Y or N501Y-E484K-K417N when compared with that of wild-type RBD (mean difference: 0.1116 and 0.5613, respectively; one-way ANOVA). Of 7 anti-N-IgG positive sera from patients infected with N501Y variants (collected 9-14 days post symptom onset), 6 (85.7%) tested negative for a commercially-available anti-S1-IgG assay. Interpretation: We highlighted the importance of using a panel of viruses within the same lineage to determine the impact of virus variants on neutralization. Furthermore, clinicians should be aware of the potential reduced sensitivity of anti-RBD IgG assays.

Original language	English
Article number	103544
Journal	eBioMedicine
Volume	71
DOIs	https://doi.org/10.1016/j.ebiom.2021.103544
Publication status	Published - Sept 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 The Author(s)

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

Keywords

B.1.351
Neutralizing antibody Spike protein receptor binding domain
SARS-CoV-2 N501Y variant B.1.1.7
VOC

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10.1016/j.ebiom.2021.103544

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Lu, L., Chu, A. W. H., Zhang, R. R., Chan, W. M., Ip, J. D., Tsoi, H. W., Chen, L. L., Cai, J. P., Lung, D. C., Tam, A. R., Yau, Y. S., Kwan, M. Y. W., To, W. K., Tsang, O. T. Y., Lee, L. L. Y., Yi, H., Ip, T. C., Poon, R. W. S., Siu, G. K. H., ... To, K. K. W. (2021). The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum. eBioMedicine, 71, Article 103544. https://doi.org/10.1016/j.ebiom.2021.103544

Lu, L, Chu, AWH, Zhang, RR, Chan, WM, Ip, JD, Tsoi, HW, Chen, LL, Cai, JP, Lung, DC, Tam, AR, Yau, YS, Kwan, MYW, To, WK, Tsang, OTY, Lee, LLY, Yi, H, Ip, TC, Poon, RWS, Siu, GKH, Mok, BWY, Cheng, VCC, Chan, KH, Yuen, KY, Hung, IFN & To, KKW 2021, 'The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum', eBioMedicine, vol. 71, 103544. https://doi.org/10.1016/j.ebiom.2021.103544

@article{dc234b65e5e248abad8fd1bae5d61307,

title = "The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum",

abstract = "Background: Several SARS-CoV-2 lineages with spike receptor binding domain (RBD) N501Y mutation have spread globally. We evaluated the impact of N501Y on neutralizing activity of COVID-19 convalescent sera and on anti-RBD IgG assays. Methods: The susceptibility to neutralization by COVID-19 patients{\textquoteright} convalescent sera from Hong Kong were compared between two SARS-CoV-2 isolates (B117-1/B117-2) from the α variant with N501Y and 4 non-N501Y isolates. The effect of N501Y on antibody binding was assessed. The performance of commercially-available IgG assays was determined for patients infected with N501Y variants. Findings: The microneutralization antibody (MN) titers of convalescent sera from 9 recovered COVID-19 patients against B117-1 (geometric mean titer[GMT],80; 95% CI, 47–136) were similar to those against the non-N501Y viruses. However, MN titer of these serum against B117-2 (GMT, 20; 95% CI, 11–36) was statistically significantly reduced when compared with non-N501Y viruses (P < 0.01; one-way ANOVA). The difference between B117-1 and B117-2 was confirmed by testing 60 additional convalescent sera. B117-1 and B117-2 differ by only 3 amino acids (nsp2-S512Y, nsp13-K460R, spike-A1056V). Enzyme immunoassay using 272 convalescent sera showed reduced binding of anti-RBD IgG to N501Y or N501Y-E484K-K417N when compared with that of wild-type RBD (mean difference: 0.1116 and 0.5613, respectively; one-way ANOVA). Of 7 anti-N-IgG positive sera from patients infected with N501Y variants (collected 9-14 days post symptom onset), 6 (85.7%) tested negative for a commercially-available anti-S1-IgG assay. Interpretation: We highlighted the importance of using a panel of viruses within the same lineage to determine the impact of virus variants on neutralization. Furthermore, clinicians should be aware of the potential reduced sensitivity of anti-RBD IgG assays.",

keywords = "B.1.351, Neutralizing antibody Spike protein receptor binding domain, SARS-CoV-2 N501Y variant B.1.1.7, VOC",

author = "Lu Lu and Chu, {Allen Wing Ho} and Zhang, {Ricky Ruiqi} and Chan, {Wan Mui} and Ip, {Jonathan Daniel} and Tsoi, {Hoi Wah} and Chen, {Lin lei} and Cai, {Jian Piao} and Lung, {David Christopher} and Tam, {Anthony Raymond} and Yau, {Yat Sun} and Kwan, {Mike Yat Wah} and To, {Wing Kin} and Tsang, {Owen Tak Yin} and Lee, {Larry Lap Yip} and Haisu Yi and Ip, {Tak Chuen} and Poon, {Rosana Wing Shan} and Siu, {Gilman Kit Hang} and Mok, {Bobo Wing Yee} and Cheng, {Vincent Chi Chung} and Chan, {Kwok Hung} and Yuen, {Kwok Yung} and Hung, {Ivan Fan Ngai} and To, {Kelvin Kai Wang}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2021",

month = sep,

doi = "10.1016/j.ebiom.2021.103544",

language = "English",

volume = "71",

journal = "eBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

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TY - JOUR

T1 - The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum

AU - Lu, Lu

AU - Chu, Allen Wing Ho

AU - Zhang, Ricky Ruiqi

AU - Chan, Wan Mui

AU - Ip, Jonathan Daniel

AU - Tsoi, Hoi Wah

AU - Chen, Lin lei

AU - Cai, Jian Piao

AU - Lung, David Christopher

AU - Tam, Anthony Raymond

AU - Yau, Yat Sun

AU - Kwan, Mike Yat Wah

AU - To, Wing Kin

AU - Tsang, Owen Tak Yin

AU - Lee, Larry Lap Yip

AU - Yi, Haisu

AU - Ip, Tak Chuen

AU - Poon, Rosana Wing Shan

AU - Siu, Gilman Kit Hang

AU - Mok, Bobo Wing Yee

AU - Cheng, Vincent Chi Chung

AU - Chan, Kwok Hung

AU - Yuen, Kwok Yung

AU - Hung, Ivan Fan Ngai

AU - To, Kelvin Kai Wang

PY - 2021/9

Y1 - 2021/9

N2 - Background: Several SARS-CoV-2 lineages with spike receptor binding domain (RBD) N501Y mutation have spread globally. We evaluated the impact of N501Y on neutralizing activity of COVID-19 convalescent sera and on anti-RBD IgG assays. Methods: The susceptibility to neutralization by COVID-19 patients’ convalescent sera from Hong Kong were compared between two SARS-CoV-2 isolates (B117-1/B117-2) from the α variant with N501Y and 4 non-N501Y isolates. The effect of N501Y on antibody binding was assessed. The performance of commercially-available IgG assays was determined for patients infected with N501Y variants. Findings: The microneutralization antibody (MN) titers of convalescent sera from 9 recovered COVID-19 patients against B117-1 (geometric mean titer[GMT],80; 95% CI, 47–136) were similar to those against the non-N501Y viruses. However, MN titer of these serum against B117-2 (GMT, 20; 95% CI, 11–36) was statistically significantly reduced when compared with non-N501Y viruses (P < 0.01; one-way ANOVA). The difference between B117-1 and B117-2 was confirmed by testing 60 additional convalescent sera. B117-1 and B117-2 differ by only 3 amino acids (nsp2-S512Y, nsp13-K460R, spike-A1056V). Enzyme immunoassay using 272 convalescent sera showed reduced binding of anti-RBD IgG to N501Y or N501Y-E484K-K417N when compared with that of wild-type RBD (mean difference: 0.1116 and 0.5613, respectively; one-way ANOVA). Of 7 anti-N-IgG positive sera from patients infected with N501Y variants (collected 9-14 days post symptom onset), 6 (85.7%) tested negative for a commercially-available anti-S1-IgG assay. Interpretation: We highlighted the importance of using a panel of viruses within the same lineage to determine the impact of virus variants on neutralization. Furthermore, clinicians should be aware of the potential reduced sensitivity of anti-RBD IgG assays.

AB - Background: Several SARS-CoV-2 lineages with spike receptor binding domain (RBD) N501Y mutation have spread globally. We evaluated the impact of N501Y on neutralizing activity of COVID-19 convalescent sera and on anti-RBD IgG assays. Methods: The susceptibility to neutralization by COVID-19 patients’ convalescent sera from Hong Kong were compared between two SARS-CoV-2 isolates (B117-1/B117-2) from the α variant with N501Y and 4 non-N501Y isolates. The effect of N501Y on antibody binding was assessed. The performance of commercially-available IgG assays was determined for patients infected with N501Y variants. Findings: The microneutralization antibody (MN) titers of convalescent sera from 9 recovered COVID-19 patients against B117-1 (geometric mean titer[GMT],80; 95% CI, 47–136) were similar to those against the non-N501Y viruses. However, MN titer of these serum against B117-2 (GMT, 20; 95% CI, 11–36) was statistically significantly reduced when compared with non-N501Y viruses (P < 0.01; one-way ANOVA). The difference between B117-1 and B117-2 was confirmed by testing 60 additional convalescent sera. B117-1 and B117-2 differ by only 3 amino acids (nsp2-S512Y, nsp13-K460R, spike-A1056V). Enzyme immunoassay using 272 convalescent sera showed reduced binding of anti-RBD IgG to N501Y or N501Y-E484K-K417N when compared with that of wild-type RBD (mean difference: 0.1116 and 0.5613, respectively; one-way ANOVA). Of 7 anti-N-IgG positive sera from patients infected with N501Y variants (collected 9-14 days post symptom onset), 6 (85.7%) tested negative for a commercially-available anti-S1-IgG assay. Interpretation: We highlighted the importance of using a panel of viruses within the same lineage to determine the impact of virus variants on neutralization. Furthermore, clinicians should be aware of the potential reduced sensitivity of anti-RBD IgG assays.

KW - B.1.351

KW - Neutralizing antibody Spike protein receptor binding domain

KW - SARS-CoV-2 N501Y variant B.1.1.7

KW - VOC

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VL - 71

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The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

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