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

TitleThe impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum
Authors
KeywordsSARS-CoV-2 N501Y variant
B.1.1.7B.1.351
Neutralizing antibody Spike protein receptor binding domain
VOC
Issue Date2021
PublisherElsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com
Citation
EBioMedicine, 2021, v. 71, p. article no. 103544 How to Cite?
AbstractBackground: 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. 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.
Persistent Identifierhttp://hdl.handle.net/10722/304562
ISSN
2023 Impact Factor: 9.7
2023 SCImago Journal Rankings: 3.193
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLu, L-
dc.contributor.authorChu, AWH-
dc.contributor.authorZhang, RR-
dc.contributor.authorChan, WM-
dc.contributor.authorIp, JD-
dc.contributor.authorTsoi, HW-
dc.contributor.authorChen, LL-
dc.contributor.authorCai, JP-
dc.contributor.authorLung, DC-
dc.contributor.authorTam, AR-
dc.contributor.authorYau, YS-
dc.contributor.authorKwan, MYW-
dc.contributor.authorTo, WK-
dc.contributor.authorTsang, OTY-
dc.contributor.authorLee, LLY-
dc.contributor.authorYi, H-
dc.contributor.authorIp, TC-
dc.contributor.authorPoon, RWS-
dc.contributor.authorSiu, GKH-
dc.contributor.authorMok, BWY-
dc.contributor.authorCheng, VCC-
dc.contributor.authorChan, KH-
dc.contributor.authorYuen, KY-
dc.contributor.authorHung, IFN-
dc.contributor.authorTo, KKW-
dc.date.accessioned2021-09-23T09:01:50Z-
dc.date.available2021-09-23T09:01:50Z-
dc.date.issued2021-
dc.identifier.citationEBioMedicine, 2021, v. 71, p. article no. 103544-
dc.identifier.issn2352-3964-
dc.identifier.urihttp://hdl.handle.net/10722/304562-
dc.description.abstractBackground: 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. 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.-
dc.languageeng-
dc.publisherElsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com-
dc.relation.ispartofEBioMedicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectSARS-CoV-2 N501Y variant-
dc.subjectB.1.1.7B.1.351-
dc.subjectNeutralizing antibody Spike protein receptor binding domain-
dc.subjectVOC-
dc.titleThe impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum-
dc.typeArticle-
dc.identifier.emailLu, L: ilulu@hku.hk-
dc.identifier.emailChu, AWH: awhchu@hku.hk-
dc.identifier.emailZhang, RR: zhangrq@hku.hk-
dc.identifier.emailChan, WM: mbally@hku.hk-
dc.identifier.emailTsoi, HW: hwtsoi@hkucc.hku.hk-
dc.identifier.emailCai, JP: caijuice@hku.hk-
dc.identifier.emailKwan, MYW: ywmkwan@hku.hk-
dc.identifier.emailPoon, RWS: rosana@hkucc.hku.hk-
dc.identifier.emailMok, BWY: bobomok@hku.hk-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailHung, IFN: ivanhung@hkucc.hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hku.hk-
dc.identifier.authorityTsoi, HW=rp00439-
dc.identifier.authorityChan, KH=rp01921-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityHung, IFN=rp00508-
dc.identifier.authorityTo, KKW=rp01384-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ebiom.2021.103544-
dc.identifier.pmid34419925-
dc.identifier.pmcidPMC8374549-
dc.identifier.scopuseid_2-s2.0-85113156448-
dc.identifier.hkuros325588-
dc.identifier.volume71-
dc.identifier.spagearticle no. 103544-
dc.identifier.epagearticle no. 103544-
dc.identifier.isiWOS:000704348400010-
dc.publisher.placeNetherlands-

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