EBioMedicine (Sep 2021)

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

Journal volume & issue
Vol. 71
p. 103544

Abstract

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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. 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.

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