Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Tingting Li; Xiaojian Han; Chenjian Gu; Hangtian Guo; Huajun Zhang; Yingming Wang; Chao Hu; Kai Wang; Fengjiang Liu; Feiyang Luo; Yanan Zhang; Jie Hu; Wang Wang; Shenglong Li; Yanan Hao; Meiying Shen; Jingjing Huang; Yingyi Long; Shuyi Song; Ruixin Wu; Song Mu; Qian Chen; Fengxia Gao; Jianwei Wang; Shunhua Long; Luo Li; Yang Wu; Yan Gao; Wei Xu; Xia Cai; Di Qu; Zherui Zhang; Hongqing Zhang; Na Li; Qingzhu Gao; Guiji Zhang; Changlong He; Wei Wang; Xiaoyun Ji; Ni Tang; Zhenghong Yuan; Youhua Xie; Haitao Yang; Bo Zhang; Ailong Huang; Aishun Jin

doi:10.1038/s41467-021-26539-7

Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants

Nat Commun. 2021 Nov 2;12(1):6304. doi: 10.1038/s41467-021-26539-7.

Authors

Tingting Li^#^{1

2}, Xiaojian Han^#^{1

2}, Chenjian Gu^#³, Hangtian Guo^#^{4

5}, Huajun Zhang^#⁶, Yingming Wang^#^{1

2}, Chao Hu^{1

2}, Kai Wang⁷, Fengjiang Liu⁴, Feiyang Luo^{1

2}, Yanan Zhang^{8

9}, Jie Hu⁷, Wang Wang^{1

2}, Shenglong Li^{1

2}, Yanan Hao^{1

2}, Meiying Shen¹⁰, Jingjing Huang^{1

2}, Yingyi Long^{1

2}, Shuyi Song^{1

2}, Ruixin Wu^{1

2}, Song Mu^{1

2}, Qian Chen^{1

2}, Fengxia Gao^{1

2}, Jianwei Wang^{1

2}, Shunhua Long^{1

2}, Luo Li^{1

2}, Yang Wu³, Yan Gao⁴, Wei Xu³, Xia Cai³, Di Qu³, Zherui Zhang^{8

9}, Hongqing Zhang^{8

9}, Na Li^{8

9}, Qingzhu Gao⁷, Guiji Zhang⁷, Changlong He⁷, Wei Wang¹¹, Xiaoyun Ji^{5

11}, Ni Tang⁷, Zhenghong Yuan³, Youhua Xie¹², Haitao Yang¹³, Bo Zhang¹⁴, Ailong Huang¹⁵, Aishun Jin^{16

17}

Affiliations

¹ Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400010, China.
² Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, 400010, China.
³ Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
⁴ Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
⁵ State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China.
⁶ State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
⁷ Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, 400010, China.
⁸ Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
⁹ University of Chinese Academy of Sciences, Beijing, 100049, China.
¹⁰ Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150000, China.
¹¹ Institute of life sciences, Chongqing Medical University, Chongqing, 400010, China.
¹² Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China. yhxie@fudan.edu.cn.
¹³ Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. yanght@shanghaitech.edu.cn.
¹⁴ Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China. zhangbo@wh.iov.cn.
¹⁵ Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, 400010, China. ahuang@cqmu.edu.cn.
¹⁶ Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400010, China. aishunjin@cqmu.edu.cn.
¹⁷ Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing, 400010, China. aishunjin@cqmu.edu.cn.

^# Contributed equally.

Abstract

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 13G9 both recognize the steric region S^470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S^450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.

Publication types

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

MeSH terms

Animals
Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / immunology
Antibodies, Neutralizing / administration & dosage
Antibodies, Neutralizing / chemistry
Antibodies, Neutralizing / immunology*
Antibodies, Viral / administration & dosage
Antibodies, Viral / chemistry
Antibodies, Viral / immunology*
Binding Sites
COVID-19 / pathology
COVID-19 / prevention & control*
COVID-19 / virology
Epitopes
Humans
Mice
Mice, Transgenic
Mutation
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology
Viral Load / drug effects
Weight Loss / drug effects

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Epitopes
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Grants and funding

X4457/Chongqing Medical University (CQMU)