The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396421003376 |
| _version_ | 1819098792846163968 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lu Lu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T00:36:37Z |
| format | Article |
| id | doaj.art-92bebd560c144436b481681070d02e46 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-22T00:36:37Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-92bebd560c144436b481681070d02e462022-12-21T18:44:47ZengElsevierEBioMedicine2352-39642021-09-0171103544The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serumLu Lu0Allen Wing-Ho Chu1Ricky Ruiqi Zhang2Wan-Mui Chan3Jonathan Daniel Ip4Hoi-Wah Tsoi5Lin-lei Chen6Jian-Piao Cai7David Christopher Lung8Anthony Raymond Tam9Yat-Sun Yau10Mike Yat-Wah Kwan11Wing-Kin To12Owen Tak-Yin Tsang13Larry Lap-Yip Lee14Haisu Yi15Tak-Chuen Ip16Rosana Wing-Shan Poon17Gilman Kit-Hang Siu18Bobo Wing-Yee Mok19Vincent Chi-Chung Cheng20Kwok Hung Chan21Kwok-Yung Yuen22Ivan Fan-Ngai Hung23Kelvin Kai-Wang To24State 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.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 ChinaDepartment 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment of Paediatrics, Queen Elizabeth Hospital, Kowloon, Hong Kong Special Administrative Region, People's Republic of ChinaDepartment of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of ChinaDepartment of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of ChinaDepartment of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of ChinaDepartment of Accident and Emergency Medicine, Tin Shui Wai Hospital, Hong Kong Special Administrative Region, People's Republic of ChinaState 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.Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of ChinaDepartment of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of ChinaDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong Special Administrative Region, People's Republic of ChinaState 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 ChinaDepartment of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of ChinaState 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 ChinaState 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 ChinaDepartment 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 ChinaState 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.http://www.sciencedirect.com/science/article/pii/S2352396421003376SARS-CoV-2 N501Y variant B.1.1.7B.1.351Neutralizing antibody Spike protein receptor binding domainVOC |
| spellingShingle | 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 The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum EBioMedicine SARS-CoV-2 N501Y variant B.1.1.7 B.1.351 Neutralizing antibody Spike protein receptor binding domain VOC |
| title | The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum |
| title_full | The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum |
| title_fullStr | The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum |
| title_full_unstemmed | The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum |
| title_short | The impact of spike N501Y mutation on neutralizing activity and RBD binding of SARS-CoV-2 convalescent serum |
| title_sort | impact of spike n501y mutation on neutralizing activity and rbd binding of sars cov 2 convalescent serum |
| topic | SARS-CoV-2 N501Y variant B.1.1.7 B.1.351 Neutralizing antibody Spike protein receptor binding domain VOC |
| url | http://www.sciencedirect.com/science/article/pii/S2352396421003376 |
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