Identification of Human Single-Domain Antibodies against SARS-CoV-2

Yanling Wu; Cheng Li; Shuai Xia; Xiaolong Tian; Yu Kong; Zhi Wang; Chenjian Gu; Rong Zhang; Chao Tu; Youhua Xie; Zhenlin Yang; Lu Lu; Shibo Jiang; Tianlei Ying

doi:10.1016/j.chom.2020.04.023

Identification of Human Single-Domain Antibodies against SARS-CoV-2

Cell Host Microbe. 2020 Jun 10;27(6):891-898.e5. doi: 10.1016/j.chom.2020.04.023. Epub 2020 May 14.

Authors

Yanling Wu¹, Cheng Li², Shuai Xia², Xiaolong Tian², Yu Kong², Zhi Wang², Chenjian Gu², Rong Zhang², Chao Tu³, Youhua Xie², Zhenlin Yang⁴, Lu Lu², Shibo Jiang², Tianlei Ying⁵

Affiliations

¹ MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: yanlingwu@fudan.edu.cn.
² MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
³ Biomissile Corporation, Shanghai 201203, China.
⁴ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁵ MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address: tlying@fudan.edu.cn.

Abstract

The worldwide spread of COVID-19 highlights the need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. The SARS-CoV-2 spike protein, containing the receptor-binding domain (RBD) and S1 subunit involved in receptor engagement, is a potential therapeutic target. We describe the development of a phage-displayed single-domain antibody library by grafting naive complementarity-determining regions (CDRs) into framework regions of a human germline immunoglobulin heavy chain variable region (IGHV) allele. Panning this library against SARS-CoV-2 RBD and S1 subunit identified fully human single-domain antibodies targeting five distinct epitopes on SARS-CoV-2 RBD with subnanomolar to low nanomolar affinities. Some of these antibodies neutralize SARS-CoV-2 by targeting a cryptic epitope located in the spike trimeric interface. Collectively, this work presents a versatile platform for rapid antibody isolation and identifies promising therapeutic anti-SARS-CoV-2 antibodies as well as the diverse immogneic profile of the spike protein.

Keywords: CR3022; RBD; SARS-CoV-2; nanobody; single-domain antibody; trimeric interface.

MeSH terms

Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / immunology
Antibodies, Neutralizing / immunology
Epitopes / immunology
Humans
Immunoglobulin Heavy Chains
Immunoglobulin Variable Region
Models, Molecular
Peptide Library*
Protein Domains
Single-Domain Antibodies / chemistry
Single-Domain Antibodies / immunology
Single-Domain Antibodies / isolation & purification*
Spike Glycoprotein, Coronavirus / chemistry

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Epitopes
Immunoglobulin Heavy Chains
Immunoglobulin Variable Region
Peptide Library
Single-Domain Antibodies
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2