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A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from indiv...

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Autores principales: Shan, Sisi, Mok, Chee Keng, Zhang, Shuyuan, Lan, Jun, Li, Jizhou, Yang, Ziqing, Wang, Ruoke, Cheng, Lin, Fang, Mengqi, Aw, Zhen Qin, Yu, Jinfang, Zhang, Qi, Shi, Xuanling, Zhang, Tong, Zhang, Zheng, Wang, Jianbin, Wang, Xinquan, Chu, Justin Jang Hann, Zhang, Linqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710476/
https://www.ncbi.nlm.nih.gov/pubmed/34966387
http://dx.doi.org/10.3389/fimmu.2021.766821
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author Shan, Sisi
Mok, Chee Keng
Zhang, Shuyuan
Lan, Jun
Li, Jizhou
Yang, Ziqing
Wang, Ruoke
Cheng, Lin
Fang, Mengqi
Aw, Zhen Qin
Yu, Jinfang
Zhang, Qi
Shi, Xuanling
Zhang, Tong
Zhang, Zheng
Wang, Jianbin
Wang, Xinquan
Chu, Justin Jang Hann
Zhang, Linqi
author_facet Shan, Sisi
Mok, Chee Keng
Zhang, Shuyuan
Lan, Jun
Li, Jizhou
Yang, Ziqing
Wang, Ruoke
Cheng, Lin
Fang, Mengqi
Aw, Zhen Qin
Yu, Jinfang
Zhang, Qi
Shi, Xuanling
Zhang, Tong
Zhang, Zheng
Wang, Jianbin
Wang, Xinquan
Chu, Justin Jang Hann
Zhang, Linqi
author_sort Shan, Sisi
collection PubMed
description As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations—K417N, E484K, and N501Y—found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.
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spelling pubmed-87104762021-12-28 A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants Shan, Sisi Mok, Chee Keng Zhang, Shuyuan Lan, Jun Li, Jizhou Yang, Ziqing Wang, Ruoke Cheng, Lin Fang, Mengqi Aw, Zhen Qin Yu, Jinfang Zhang, Qi Shi, Xuanling Zhang, Tong Zhang, Zheng Wang, Jianbin Wang, Xinquan Chu, Justin Jang Hann Zhang, Linqi Front Immunol Immunology As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations—K417N, E484K, and N501Y—found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants. Frontiers Media S.A. 2021-12-13 /pmc/articles/PMC8710476/ /pubmed/34966387 http://dx.doi.org/10.3389/fimmu.2021.766821 Text en Copyright © 2021 Shan, Mok, Zhang, Lan, Li, Yang, Wang, Cheng, Fang, Aw, Yu, Zhang, Shi, Zhang, Zhang, Wang, Wang, Chu and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Shan, Sisi
Mok, Chee Keng
Zhang, Shuyuan
Lan, Jun
Li, Jizhou
Yang, Ziqing
Wang, Ruoke
Cheng, Lin
Fang, Mengqi
Aw, Zhen Qin
Yu, Jinfang
Zhang, Qi
Shi, Xuanling
Zhang, Tong
Zhang, Zheng
Wang, Jianbin
Wang, Xinquan
Chu, Justin Jang Hann
Zhang, Linqi
A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
title A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
title_full A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
title_fullStr A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
title_full_unstemmed A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
title_short A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
title_sort potent and protective human neutralizing antibody against sars-cov-2 variants
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710476/
https://www.ncbi.nlm.nih.gov/pubmed/34966387
http://dx.doi.org/10.3389/fimmu.2021.766821
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