Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein
Open accessAbstract
The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.
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Polyclonal antibodies against multiple non-RBD spike epitopes might block viral attachment, add neutralizing activity, or prevent post-attachment fusion.
“A polyclonal antibody against multiple epitopes of the S protein beyond the RBD might, for example, inhibit viral attachment156–160, provide additional neutralizing activity161 and/or prevent post-attachment fusion162.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [162]
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References 48 · Cited by 115
Research works printed but not linked: 1
- [30]Wang L., Shi W., Chappell J. D., Joyce M. G., Zhang Y., Kanekiyo M., Becker M. M., van Doremalen N., Fischer R., Wang N., Corbett K. S., Choe M., Mason R. D., Van Galen J. G., Zhou T., Saunders K. O., Tatti K. M., Haynes L. M., Kwong P. D., Modjarrad K., Kong W. P., McLellan J. S., Denison M. R., Munster V. J., Mascola J. R., and Graham B. S. 2018 Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on MERS-CoV spike to avoid neutralization escape. J. Virol. doi: JVI.02002-17 [pii]. PMC5923077 29514901
- Authors
- Widjaja, I., Wang, C., van Haperen, R., Gutiérrez-Álvarez, J., van Dieren, B., Okba, N. M. A., Raj, V. S., Li, W., Fernandez-Delgado, R., Grosveld, F., van Kuppeveld, F. J. M., Haagmans, B. L., Enjuanes, L., Drabek, D., & Bosch, B.-J.
- Affiliations
- Utrecht University (NL)
- Department of Cell Biology, Erasmus MC
- Department of Molecular and Cell Biology, National Center for Biotechnology-Spanish National Research Council (CNB-CSIC)
- Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University
- Erasmus MC (NL)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Bosch, Berend-Jan
- ORCID
- Venue
- Emerging Microbes & Infections
- Publisher
- Informa UK Limited
- Published
- 2019-01
- Volume
- 8
- Issue
- 1
- Pages
- 516-530
- ISSN
- 2222-1751 (ISSN-L)
- PMC
- PMC6455120
- OpenAlex
- W2932403381
- Cited by
- 115
- References
- 48
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 14 · 2021: 28 · 2020: 50 · 2019: 7
- FWCI
- 18.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Emerging Microbes & Infections (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- Figshare (cc-by)
- Funders
- European Federation of Pharmaceutical Industries and Associations
- NIH (2PO1AIO6O699)
- Center for Scientific Review
- China Scholarship Council
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- MERS-CoV, human monoclonal antibodies, spike protein, passive immunization, sialic acid binding, receptor binding domain, membrane fusion, humoral immunity, antibody-based therapy
- MeSH terms
- Protein Domains, Animals, Antibodies, Monoclonal, Antibodies, Viral, Epitopes, Humans, Immunization, Passive, Receptors, Virus, Coronavirus Infections, Mice, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus, Middle East Respiratory Syndrome Coronavirus
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