A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo

Fanlin Li; Wei Xu; Xiaoqing Zhang; Wanting Wang; Shan Su; Ping Han; Haiyong Wang; Yanqin Xu; Min Li; Lilv Fan; Huihui Zhang; Qiang Dai; Hao Lin; Xinyue Qi; Jie Liang; Xin Wang; Shibo Jiang; Youhua Xie; Lu Lu; Xuanming Yang

doi:10.1038/s42003-023-04955-3

A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo

Commun Biol. 2023 Jun 1;6(1):592. doi: 10.1038/s42003-023-04955-3.

Authors

Fanlin Li^#^{1

2}, Wei Xu^#³, Xiaoqing Zhang^#^{1

4}, Wanting Wang^#^{1

2}, Shan Su³, Ping Han^{1

2}, Haiyong Wang^{1

2}, Yanqin Xu^{1

2}, Min Li^{1

2}, Lilv Fan^{1

2}, Huihui Zhang^{1

2}, Qiang Dai^{1

2}, Hao Lin^{1

2}, Xinyue Qi^{1

2}, Jie Liang^{1

2}, Xin Wang⁵, Shibo Jiang³, Youhua Xie⁶, Lu Lu⁷, Xuanming Yang^{8

9}

Affiliations

¹ Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
² Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China.
³ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Fudan University, Shanghai, 200032, China.
⁴ Department of Physiology, Naval Medical University, Shanghai, 200433, China.
⁵ Shanghai Longyao Biotechnology Limited, Shanghai, 201203, China.
⁶ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Fudan University, Shanghai, 200032, China. yhxie@fudan.edu.cn.
⁷ Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Fudan University, Shanghai, 200032, China. lul@fudan.edu.cn.
⁸ Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China. xuanmingyang@sjtu.edu.cn.
⁹ Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China. xuanmingyang@sjtu.edu.cn.

^# Contributed equally.

Abstract

Neutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with live SARS-COV-2 infection, S-BiTE treated mice showed significantly less viral load than neutralization only treated group. The S-BiTE strategy may have broad applications in combating other coronavirus infections.

Publication types

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

MeSH terms

Animals
Antibodies, Viral
COVID-19*
Mice
Neutralization Tests
RNA, Viral
SARS-CoV-2
T-Lymphocytes

Substances

Antibodies, Viral
RNA, Viral

Supplementary concepts

SARS-CoV-2 variants