Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV
Lili Wang,
Jiyan Xu,
Yu Kong,
Ruiying Liang,
Wei Li,
Jinyao Li,
Jun Lu,
Dimiter S. Dimitrov,
Fei Yu,
Yanling Wu,
Tianlei Ying
Affiliations
Lili Wang
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
Jiyan Xu
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
Yu Kong
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
Ruiying Liang
College of Life and Science, Hebei Agricultural University, Baoding 071001, China
Wei Li
Center for Antibody Therapeutics, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA
Jinyao Li
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, China
Jun Lu
School of Science, and School of Interprofessional Health Studies, Faculty of Health & Environmental Sciences, Auckland University of Technology, Auckland 1142, New Zealand
Dimiter S. Dimitrov
Center for Antibody Therapeutics, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA
Fei Yu
College of Life and Science, Hebei Agricultural University, Baoding 071001, China
Yanling Wu
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
Tianlei Ying
MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
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.
