A non-competing pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Abstract Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design.One Sentence Summary A pair of human neutralizing monoclonal antibodies against COVID-19 compete cellular receptor binding but with different epitopes, and with post-exposure viral load reduction activity..

Medienart:

Preprint

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

bioRxiv.org - (2022) vom: 23. Okt. Zur Gesamtaufnahme - year:2022

Sprache:

Englisch

Beteiligte Personen:

Wu, Yan [VerfasserIn]
Wang, Feiran [VerfasserIn]
Shen, Chenguang [VerfasserIn]
Peng, Weiyu [VerfasserIn]
Li, Delin [VerfasserIn]
Zhao, Cheng [VerfasserIn]
Li, Zhaohui [VerfasserIn]
Li, Shihua [VerfasserIn]
Bi, Yuhai [VerfasserIn]
Yang, Yang [VerfasserIn]
Gong, Yuhuan [VerfasserIn]
Xiao, Haixia [VerfasserIn]
Fan, Zheng [VerfasserIn]
Tan, Shuguang [VerfasserIn]
Wu, Guizhen [VerfasserIn]
Tan, Wenjie [VerfasserIn]
Lu, Xuancheng [VerfasserIn]
Fan, Changfa [VerfasserIn]
Wang, Qihui [VerfasserIn]
Liu, Yingxia [VerfasserIn]
Zhang, Chen [VerfasserIn]
Qi, Jianxun [VerfasserIn]
Gao, George Fu [VerfasserIn]
Gao, Feng [VerfasserIn]
Liu, Lei [VerfasserIn]

Links:

Volltext [kostenfrei]

Themen:

570
Biology

doi:

10.1101/2020.05.01.20077743

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI017768160