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Engineering a Novel Antibody-peptide Bispecific Fusion Protein Against MERS-CoV

Wang, L; Xu, J; Kong, Y; Liang, R; Li, W; Li, J; Lu, J; Dimitrov, DS; Yu, F; Wu, Y; Ying, T
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http://hdl.handle.net/10292/13463
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Abstract
In recent years, tremendous efforts have been made in the engineering of bispecific or multi-specific antibody-based therapeutics by combining two or more functional antigen-recognizing elements into a single construct. However, to the best of our knowledge there has been no reported cases of effective antiviral antibody-peptide bispecific fusion proteins. We previously developed potent fully human monoclonal antibodies and inhibitory peptides against Middle East Respiratory Syndrome Coronavirus (MERS-CoV), a novel coronavirus that causes severe acute respiratory illness with high mortality. Here, we describe the generation of antibody-peptide bispecific fusion proteins, each of which contains an anti-MERS-CoV single-chain antibody m336 (or normal human IgG1 CH3 domain as a control) linked with, or without, a MERS-CoV fusion inhibitory peptide HR2P. We found that one of these fusion proteins, designated as m336 diabody-pep, exhibited more potent inhibitory activity than the antibody or the peptide alone against pseudotyped MERS-CoV infection and MERS-CoV S protein-mediated cell-cell fusion, suggesting its potential to be developed as an effective bispecific immunotherapeutic for clinical use.
Keywords
MERS-CoV; Bispecific; Immunotherapeutics; mAbs; Polypeptides
Date
2019
Source
Antibodies 2019, 8(4), 53; https://doi.org/10.3390/antib8040053
Item Type
Journal Article
Publisher
MDPI AG
DOI
10.3390/antib8040053
Publisher's Version
https://www.mdpi.com/2073-4468/8/4/53
Rights Statement
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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