Journal Article

Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7

Yu, Jian, Huang, Yaoxing, Zhang, Baoshan, Nair, Manoj S., Sobieszczyk, Magdalena, Liu, Lihong, Luo, Yang, Mascola, John R., Kwong, Peter D., Guo, Yicheng, Yin, Michael T., Chang, Jennifer Y., Graham, Barney S., Sheng, Zizhang, Iketani, Sho, Ho, David D., Wang, Maple, Shapiro, Lawrence, Kyratsous, Christos A., Wang, Pengfei

2021

Overview

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 authorization 1 – 3 , and more treatments are under development 4 – 7 . Furthermore, multiple vaccine constructs have shown promise 8 , including two that have an approximately 95% protective efficacy against COVID-19 9 , 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 UK 11 and B.1.351 in South Africa 12 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 variants 13 , 14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines. The SARS-CoV-2 variant B.1.1.7 can be neutralized by convalescent sera or sera from vaccinated individuals, whereas the B.1.351 variant is resistant to neutralization by these sera and by several monoclonal antibodies that are in clinical use.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 631/250/255 / 631/250/590 / 631/326/596/4130 / Adult / Aged / Animals / Antibodies, Monoclonal - immunology / Antibodies, Monoclonal - therapeutic use / Antibodies, Neutralizing - immunology / Antibodies, Viral - immunology / Binding / Binding sites / Chlorocebus aethiops / Coronaviruses / COVID-19 / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 - therapy / COVID-19 - virology / COVID-19 Drug Treatment / COVID-19 Serotherapy / COVID-19 vaccines / COVID-19 Vaccines - immunology / Drug Resistance, Viral - immunology / HEK293 Cells / Humanities and Social Sciences / Humans / Immune Evasion - genetics / Immune Evasion - immunology / Immunization, Passive / Immunotherapy / Middle Aged / Models, Molecular / Monoclonal antibodies / mRNA Vaccines / multidisciplinary / Mutation / Neutralization / Neutralization Tests / Pandemics / Protein Domains - immunology / Proteins / Receptors / SARS-CoV-2 - chemistry / SARS-CoV-2 - genetics / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - chemistry / Spike Glycoprotein, Coronavirus - genetics / Spike Glycoprotein, Coronavirus - immunology / Spike protein / Vaccines / Vaccines, Synthetic - immunology / Vero Cells / Viral diseases / Viruses