期刊
EBIOMEDICINE
卷 71, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2021.103544
关键词
SARS-CoV-2 N501Y variant B.1.1.7; B.1.351; Neutralizing antibody Spike protein receptor binding domain; VOC
资金
- Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance, Department of Health, Hong Kong SAR Government
The study demonstrates that the N501Y mutation has a significant impact on neutralizing activity of COVID-19 convalescent sera and anti-RBD IgG assays. Patients infected with N501Y variants may exhibit reduced antibody binding and lower positivity rates in IgG assays.
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 a variant with N501Y and 4 nonN501Y 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. Funding: Richard and Carol Yu, Michael Tong, and the Government Consultancy Service (see acknowledgments for full list). 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. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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