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Characterization of a human-mouse chimeric monoclonal antibody targeting rabies virus glycoprotein
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  • Meina Cai,
  • Ziliang Hu,
  • Yi Yang,
  • Ting Mao,
  • Yacui Liu,
  • Guangwen Lu,
  • Fanli Yang,
  • Jianxun Qi,
  • Weijin Huang,
  • Youchun Wang
Meina Cai
National Institutes for Food and Drug Control
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Ziliang Hu
Anhui University Institute of Physical Science and Information Technology
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Yi Yang
Biocytogen Pharmaceuticals (Beijing) Co Ltd
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Ting Mao
Biocytogen Pharmaceuticals (Beijing) Co Ltd
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Yacui Liu
Biocytogen Pharmaceuticals (Beijing) Co Ltd
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Guangwen Lu
Sichuan University West China Hospital
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Fanli Yang
Sichuan University West China Hospital
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Jianxun Qi
University of Chinese Academy of Sciences
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Weijin Huang
National Institutes for Food and Drug Control
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Youchun Wang
National Institutes for Food and Drug Control

Corresponding Author:wangyc@nifdc.org.cn

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Abstract

At present, the horse or human rabies immunoglobulin (RIG) used for post-exposure prevention of human rabies (PEP) has high cost and limited availability. It is strongly encouraged to replace RIG with equivalent or more effective and safer products. Mouse and human monoclonal antibodies have been shown to protect rodents from lethal rabies virus (RABV) attacks. In this study, we reported a human-mouse chimeric monoclonal antibody, 12-2A12, which showed a strong neutralization potency and a wide breadth against multiple street viruses of RABV in vitro. The antibody binds the viral glycoprotein (G) with nanomolar affinity. The complex structure of 12-2A12 bound to RABV G reveals that the antibody recognizes an epitope that partially overlaps with the recognition region for the nicotinic acetylcholine receptor (nAChR). The antibody therefore would interfere with the nAChR/G interaction to block the viral receptor binding. In addition, comparison of our complex structure with the G structure in the acidic state reveals a clear steric clash, highlighting that the antibody would further prevent the conformational changes of the viral glycoprotein that are essential for membrane fusion. In light of these functional and structural data, we believe that 12-2A12 might be developed to be included in an antibody cocktail for potential use in human rabies PEP.
03 Apr 2023Submitted to Journal of Medical Virology
07 Apr 2023Submission Checks Completed
07 Apr 2023Assigned to Editor
07 Apr 2023Review(s) Completed, Editorial Evaluation Pending
12 Apr 2023Reviewer(s) Assigned
04 Jun 2023Editorial Decision: Revise Minor
29 Jun 20231st Revision Received
30 Jun 2023Review(s) Completed, Editorial Evaluation Pending
30 Jun 2023Submission Checks Completed
30 Jun 2023Assigned to Editor
30 Jun 2023Editorial Decision: Accept