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Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7.
Nature. 2021 05; 593(7857):130-135.Nat

Abstract

The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization1-3, and more treatments are under development4-7. Furthermore, multiple vaccine constructs have shown promise8, including two that have an approximately 95% protective efficacy against COVID-199,10. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.

Authors+Show Affiliations

Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA. Department of Biochemistry, Columbia University, New York, NY, USA.Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Regeneron Pharmaceuticals, Tarrytown, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. Department of Biochemistry, Columbia University, New York, NY, USA. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. yh3253@cumc.columbia.edu.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. dh2994@cumc.columbia.edu. Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA. dh2994@cumc.columbia.edu. Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. dh2994@cumc.columbia.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33684923

Citation

Wang, Pengfei, et al. "Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7." Nature, vol. 593, no. 7857, 2021, pp. 130-135.
Wang P, Nair MS, Liu L, et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature. 2021;593(7857):130-135.
Wang, P., Nair, M. S., Liu, L., Iketani, S., Luo, Y., Guo, Y., Wang, M., Yu, J., Zhang, B., Kwong, P. D., Graham, B. S., Mascola, J. R., Chang, J. Y., Yin, M. T., Sobieszczyk, M., Kyratsous, C. A., Shapiro, L., Sheng, Z., Huang, Y., & Ho, D. D. (2021). Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature, 593(7857), 130-135. https://doi.org/10.1038/s41586-021-03398-2
Wang P, et al. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. Nature. 2021;593(7857):130-135. PubMed PMID: 33684923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. AU - Wang,Pengfei, AU - Nair,Manoj S, AU - Liu,Lihong, AU - Iketani,Sho, AU - Luo,Yang, AU - Guo,Yicheng, AU - Wang,Maple, AU - Yu,Jian, AU - Zhang,Baoshan, AU - Kwong,Peter D, AU - Graham,Barney S, AU - Mascola,John R, AU - Chang,Jennifer Y, AU - Yin,Michael T, AU - Sobieszczyk,Magdalena, AU - Kyratsous,Christos A, AU - Shapiro,Lawrence, AU - Sheng,Zizhang, AU - Huang,Yaoxing, AU - Ho,David D, Y1 - 2021/03/08/ PY - 2021/01/25/received PY - 2021/02/25/accepted PY - 2021/3/9/pubmed PY - 2021/5/12/medline PY - 2021/3/8/entrez SP - 130 EP - 135 JF - Nature JO - Nature VL - 593 IS - 7857 N2 - The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization1-3, and more treatments are under development4-7. Furthermore, multiple vaccine constructs have shown promise8, including two that have an approximately 95% protective efficacy against COVID-199,10. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/33684923/Antibody_resistance_of_SARS_CoV_2_variants_B_1_351_and_B_1_1_7_ L2 - https://doi.org/10.1038/s41586-021-03398-2 DB - PRIME DP - Unbound Medicine ER -