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10.1016/j.ebiom.2021.103544

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34419925!8374549!34419925
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suck abstract from ncbi


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pmid34419925      EBioMedicine 2021 ; 71 (ä): 103544
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  • The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum #MMPMID34419925
  • Lu L; Chu AW; Zhang RR; Chan WM; Ip JD; Tsoi HW; Chen LL; Cai JP; Lung DC; Tam AR; Yau YS; Kwan MY; To WK; Tsang OT; Lee LL; Yi H; Ip TC; Poon RW; Siu GK; Mok BW; Cheng VC; Chan KH; Yuen KY; Hung IF; To KK
  • EBioMedicine 2021[Sep]; 71 (ä): 103544 PMID34419925show ga
  • 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 alpha 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.
  • |Adult[MESH]
  • |Aged[MESH]
  • |Antibodies, Neutralizing/administration & dosage/immunology[MESH]
  • |Antibodies, Viral/administration & dosage/ultrastructure[MESH]
  • |COVID-19 Serotherapy[MESH]
  • |COVID-19/genetics/immunology/*therapy/virology[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Immunization, Passive[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Mutation/genetics[MESH]
  • |Neutralization Tests[MESH]
  • |SARS-CoV-2/*genetics/immunology/pathogenicity[MESH]


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