Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV
Identifieur interne : 000600 ( Main/Exploration ); précédent : 000599; suivant : 000601Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV
Auteurs : Lili Wang [République populaire de Chine] ; Jiyan Xu ; Yu Kong ; Ruiying Liang ; Wei Li ; Jinyao Li ; Jun Lu ; Dimiter S. Dimitrov ; Fei Yu ; Yanling Wu ; Tianlei YingSource :
- Antibodies [ 2073-4468 ] ; 2019.
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.
Url:
DOI: 10.3390/antib8040053
PubMed: 31690009
PubMed Central: 6963733
Affiliations:
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Dimitrov</name><affiliation><nlm:aff id="af4-antibodies-08-00053">Center for Antibody Therapeutics, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA;<email>LIWEI171@pitt.edu</email> (W.L.);<email>dsd116@pitt.edu</email> (D.S.D.)</nlm:aff></affiliation></author><author><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name><affiliation><nlm:aff id="af3-antibodies-08-00053">College of Life and Science, Hebei Agricultural University, Baoding 071001, China;<email>ruiyingliang@outlook.com</email></nlm:aff></affiliation></author><author><name sortKey="Wu, Yanling" sort="Wu, Yanling" uniqKey="Wu Y" first="Yanling" last="Wu">Yanling Wu</name><affiliation><nlm:aff id="af1-antibodies-08-00053">MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China;<email>liliwang@fudan.edu.cn</email> (L.W.);<email>13301050116@fudan.edu.cn</email> (J.X.);<email>kongyu@fudan.edu.cn</email> (Y.K.);<email>tlying@fudan.edu.cn</email> (T.Y.)</nlm:aff></affiliation></author><author><name sortKey="Ying, Tianlei" sort="Ying, Tianlei" uniqKey="Ying T" first="Tianlei" last="Ying">Tianlei Ying</name><affiliation><nlm:aff id="af1-antibodies-08-00053">MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China;<email>liliwang@fudan.edu.cn</email> (L.W.);<email>13301050116@fudan.edu.cn</email> (J.X.);<email>kongyu@fudan.edu.cn</email> (Y.K.);<email>tlying@fudan.edu.cn</email> (T.Y.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31690009</idno><idno type="pmc">6963733</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963733</idno><idno type="RBID">PMC:6963733</idno><idno type="doi">10.3390/antib8040053</idno><date when="2019">2019</date><idno 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id="af2-antibodies-08-00053">Research Center of Chinese Jujube, Hebei Agricultural University, Baoding 071001, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Research Center of Chinese Jujube, Hebei Agricultural University, Baoding 071001</wicri:regionArea><wicri:noRegion>Baoding 071001</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Jiyan" sort="Xu, Jiyan" uniqKey="Xu J" first="Jiyan" last="Xu">Jiyan Xu</name><affiliation><nlm:aff id="af1-antibodies-08-00053">MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China;<email>liliwang@fudan.edu.cn</email> (L.W.);<email>13301050116@fudan.edu.cn</email> (J.X.);<email>kongyu@fudan.edu.cn</email> (Y.K.);<email>tlying@fudan.edu.cn</email> (T.Y.)</nlm:aff></affiliation></author><author><name sortKey="Kong, Yu" sort="Kong, Yu" uniqKey="Kong Y" first="Yu" last="Kong">Yu Kong</name><affiliation><nlm:aff id="af1-antibodies-08-00053">MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China;<email>liliwang@fudan.edu.cn</email> (L.W.);<email>13301050116@fudan.edu.cn</email> (J.X.);<email>kongyu@fudan.edu.cn</email> (Y.K.);<email>tlying@fudan.edu.cn</email> (T.Y.)</nlm:aff></affiliation></author><author><name sortKey="Liang, Ruiying" sort="Liang, Ruiying" uniqKey="Liang R" first="Ruiying" last="Liang">Ruiying Liang</name><affiliation><nlm:aff id="af3-antibodies-08-00053">College of Life and Science, Hebei Agricultural University, Baoding 071001, China;<email>ruiyingliang@outlook.com</email></nlm:aff></affiliation></author><author><name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name><affiliation><nlm:aff id="af4-antibodies-08-00053">Center for Antibody Therapeutics, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA;<email>LIWEI171@pitt.edu</email> (W.L.);<email>dsd116@pitt.edu</email> (D.S.D.)</nlm:aff></affiliation></author><author><name sortKey="Li, Jinyao" sort="Li, Jinyao" uniqKey="Li J" first="Jinyao" last="Li">Jinyao Li</name><affiliation><nlm:aff id="af5-antibodies-08-00053">Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830046, China;<email>ljyxju@xju.edu.cn</email></nlm:aff></affiliation></author><author><name sortKey="Lu, Jun" sort="Lu, Jun" uniqKey="Lu J" first="Jun" last="Lu">Jun Lu</name><affiliation><nlm:aff id="af6-antibodies-08-00053">School of Science, and School of Interprofessional Health Studies, Faculty of Health & Environmental Sciences, Auckland University of Technology, Auckland 1142, New Zealand;<email>jun.lu@aut.ac.nz</email></nlm:aff></affiliation></author><author><name sortKey="Dimitrov, Dimiter S" sort="Dimitrov, Dimiter S" uniqKey="Dimitrov D" first="Dimiter S." last="Dimitrov">Dimiter S. Dimitrov</name><affiliation><nlm:aff id="af4-antibodies-08-00053">Center for Antibody Therapeutics, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA;<email>LIWEI171@pitt.edu</email> (W.L.);<email>dsd116@pitt.edu</email> (D.S.D.)</nlm:aff></affiliation></author><author><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name><affiliation><nlm:aff id="af3-antibodies-08-00053">College of Life and Science, Hebei Agricultural University, Baoding 071001, China;<email>ruiyingliang@outlook.com</email></nlm:aff></affiliation></author><author><name sortKey="Wu, Yanling" sort="Wu, Yanling" uniqKey="Wu Y" first="Yanling" last="Wu">Yanling Wu</name><affiliation><nlm:aff id="af1-antibodies-08-00053">MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China;<email>liliwang@fudan.edu.cn</email> (L.W.);<email>13301050116@fudan.edu.cn</email> (J.X.);<email>kongyu@fudan.edu.cn</email> (Y.K.);<email>tlying@fudan.edu.cn</email> (T.Y.)</nlm:aff></affiliation></author><author><name sortKey="Ying, Tianlei" sort="Ying, Tianlei" uniqKey="Ying T" first="Tianlei" last="Ying">Tianlei Ying</name><affiliation><nlm:aff id="af1-antibodies-08-00053">MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China;<email>liliwang@fudan.edu.cn</email> (L.W.);<email>13301050116@fudan.edu.cn</email> (J.X.);<email>kongyu@fudan.edu.cn</email> (Y.K.);<email>tlying@fudan.edu.cn</email> (T.Y.)</nlm:aff></affiliation></author></analytic><series><title level="j">Antibodies</title><idno type="eISSN">2073-4468</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zhu, Z" uniqKey="Zhu Z">Z. Zhu</name></author><author><name sortKey="Dimitrov, A S" uniqKey="Dimitrov A">A.S. Dimitrov</name></author><author><name sortKey="Bossart, K N" uniqKey="Bossart K">K.N. Bossart</name></author><author><name sortKey="Crameri, G" uniqKey="Crameri G">G. Crameri</name></author><author><name sortKey="Bishop, K A" uniqKey="Bishop K">K.A. Bishop</name></author><author><name sortKey="Choudhry, V" uniqKey="Choudhry V">V. 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Dimitrov</name><name sortKey="Kong, Yu" sort="Kong, Yu" uniqKey="Kong Y" first="Yu" last="Kong">Yu Kong</name><name sortKey="Li, Jinyao" sort="Li, Jinyao" uniqKey="Li J" first="Jinyao" last="Li">Jinyao Li</name><name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name><name sortKey="Liang, Ruiying" sort="Liang, Ruiying" uniqKey="Liang R" first="Ruiying" last="Liang">Ruiying Liang</name><name sortKey="Lu, Jun" sort="Lu, Jun" uniqKey="Lu J" first="Jun" last="Lu">Jun Lu</name><name sortKey="Wu, Yanling" sort="Wu, Yanling" uniqKey="Wu Y" first="Yanling" last="Wu">Yanling Wu</name><name sortKey="Xu, Jiyan" sort="Xu, Jiyan" uniqKey="Xu J" first="Jiyan" last="Xu">Jiyan Xu</name><name sortKey="Ying, Tianlei" sort="Ying, Tianlei" uniqKey="Ying T" first="Tianlei" last="Ying">Tianlei Ying</name><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Lili" sort="Wang, Lili" uniqKey="Wang L" first="Lili" last="Wang">Lili Wang</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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