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.
Fanlin Li  #  1  2 ,  Wei Xu  #  3 ,  Xiaoqing Zhang  #  1  4 ,  Wanting Wang  #  1  2 ,  Shan Su  3 ,  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 Wang  5 ,  Shibo Jiang  3 ,  Youhua Xie  6 ,  Lu Lu  7 ,  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. [email protected].
  • 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. [email protected].
  • 8. Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China. [email protected].
  • 9. Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, 200240, China. [email protected].
  • # Contributed equally.
PMID: 37264086 DOI: 10.1038/s42003-023-04955-3
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.

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