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The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum.
Lu, Lu; Chu, Allen Wing-Ho; Zhang, Ricky Ruiqi; Chan, Wan-Mui; Ip, Jonathan Daniel; Tsoi, Hoi-Wah; Chen, Lin-Lei; Cai, Jian-Piao; Lung, David Christopher; Tam, Anthony Raymond; Yau, Yat-Sun; Kwan, Mike Yat-Wah; To, Wing-Kin; Tsang, Owen Tak-Yin; Lee, Larry Lap-Yip; Yi, Haisu; Ip, Tak-Chuen; Poon, Rosana Wing-Shan; Siu, Gilman Kit-Hang; Mok, Bobo Wing-Yee; Cheng, Vincent Chi-Chung; Chan, Kwok Hung; Yuen, Kwok-Yung; Hung, Ivan Fan-Ngai; To, Kelvin Kai-Wang.
  • Lu L; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Chu AW; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Zhang RR; Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Chan WM; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Ip JD; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Tsoi HW; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Chen LL; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Cai JP; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Lung DC; Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong Special Administrative Region, People's Republic of China; Department of Pathology, Hong Kong Children's Hospital, Kowloon, Hong Kong Special Administrative Region, People's Republic of China.
  • Tam AR; Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Yau YS; Department of Paediatrics, Queen Elizabeth Hospital, Kowloon, Hong Kong Special Administrative Region, People's Republic of China.
  • Kwan MY; Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China.
  • To WK; Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China.
  • Tsang OT; Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China.
  • Lee LL; Department of Accident and Emergency Medicine, Tin Shui Wai Hospital, Hong Kong Special Administrative Region, People's Republic of China.
  • Yi H; State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Ip TC; Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
  • Poon RW; Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
  • Siu GK; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong Special Administrative Region, People's Republic of China.
  • Mok BW; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Cheng VC; Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China.
  • Chan KH; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • Yuen KY; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Queen Mary Hospit
  • Hung IF; Department of Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
  • To KK; State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Queen Mary Hospit
EBioMedicine ; 71: 103544, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363987
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.

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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Topics: Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: EBioMedicine Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Topics: Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: EBioMedicine Year: 2021 Document Type: Article