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

Wang, Lili and Xu, Jiyan and Kong, Yu and Liang, Ruiying and Li, Wei and Li, Jinyao and Lu, Jun and Dimitrov, Dimiter S. and Yu, Fei and Wu, Yanling and Ying, Tianlei (2019) Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV. Antibodies, 8 (4). p. 53. ISSN 2073-4468

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wang, Lili
Xu, Jiyan
Kong, Yu
Liang, Ruiying
Li, Weiliwei171@pitt.eduliwei171
Li, Jinyao
Lu, Jun
Dimitrov, Dimiter S.
Yu, Fei
Wu, Yanling
Ying, Tianlei
Date: 4 November 2019
Date Type: Publication
Journal or Publication Title: Antibodies
Volume: 8
Number: 4
Publisher: MDPI AG
Page Range: p. 53
DOI or Unique Handle: 10.3390/antib8040053
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Uncontrolled Keywords: mers-cov, mabs, polypeptides, bispecific, immunotherapeutics
ISSN: 2073-4468
Official URL: http://dx.doi.org/10.3390/antib8040053
Funders: National Natural Science Foundation of China, Chinese Academy of Medical Sciences, Fudan’s Undergraduate Research Opportunities Program, Hebei Agricultural University, National Fundamental Fund of Training Basic Science, Program for Talents Introduction from studying overseas of Hebei Province, Program for Youth Talent of Higher Learning Institutions of Hebei Province, National Megaprojects of China for Major Infectious Diseases, New Zealand Ministry of Education’s New Zealand-China Tripartite Partnership Fund
Article Type: Research Article
Date Deposited: 14 May 2021 19:46
Last Modified: 14 May 2021 19:46
URI: http://d-scholarship.pitt.edu/id/eprint/41092

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