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
Affiliations
Lu Lu
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; Corresponding authors at: 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.
Allen Wing-Ho Chu
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
Ricky Ruiqi Zhang
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
Wan-Mui Chan
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
Jonathan Daniel Ip
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
Hoi-Wah Tsoi
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
Lin-lei Chen
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
Jian-Piao Cai
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
David Christopher Lung
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
Anthony Raymond Tam
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
Yat-Sun Yau
Department of Paediatrics, Queen Elizabeth Hospital, Kowloon, Hong Kong Special Administrative Region, People's Republic of China
Mike Yat-Wah Kwan
Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China
Wing-Kin To
Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China
Owen Tak-Yin Tsang
Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China
Larry Lap-Yip Lee
Department of Accident and Emergency Medicine, Tin Shui Wai Hospital, Hong Kong Special Administrative Region, People's Republic of China
Haisu Yi
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.
Tak-Chuen Ip
Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China
Rosana Wing-Shan Poon
Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China
Gilman Kit-Hang Siu
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong Special Administrative Region, People's Republic of China
Bobo Wing-Yee Mok
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
Vincent Chi-Chung Cheng
Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China
Kwok Hung Chan
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
Kwok-Yung Yuen
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 Hospital, Hong Kong Special Administrative Region, People's Republic of China
Ivan Fan-Ngai Hung
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
Kelvin Kai-Wang To
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 Hospital, Hong Kong Special Administrative Region, People's Republic of China; Corresponding authors at: 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.
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.
