1. Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant
- Author
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Laura E. McCoy, Jeffrey Seow, Thomas A. Bowden, Helen M. E. Duyvesteyn, Jose M. Jimenez-Guardeño, Hataf Khan, Neophytos Kouphou, Yuguang Zhao, Marit J. van Gils, Yin Wu, Carl Graham, Peter Cherepanov, Maria Jose Lista, Adam Laing, Manu Shankar-Hari, Liane Dupont, Weng M Ng, Adrian Hayday, Stuart J. D. Neil, Michael H. Malim, Luke Muir, Sam Acors, Annachiara Rosa, Magdalene Joseph, Helena Winstone, Katie J. Doores, Rui Pedro Galão, Isabella Huettner, Suzanne Pickering, Medical Microbiology and Infection Prevention, and AII - Infectious diseases
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Models, Molecular ,0301 basic medicine ,COVID-19/diagnosis ,Protein Conformation ,Antibodies, Viral ,Epitopes/chemistry ,Neutralization ,Epitope ,Epitopes ,0302 clinical medicine ,antibody ,Antibodies, Viral/chemistry ,Immunology and Allergy ,Protein Binding/immunology ,biology ,Antibodies, Monoclonal ,Antibodies, Neutralizing/immunology ,neutralizing epitope ,Infectious Diseases ,Angiotensin-Converting Enzyme 2/chemistry ,030220 oncology & carcinogenesis ,Spike Glycoprotein, Coronavirus ,Angiotensin-Converting Enzyme 2 ,Antibody ,variant of concern ,Protein Binding ,Antigenicity ,Subdominant ,medicine.drug_class ,Immunology ,Antibodies, Monoclonal/chemistry ,Cross Reactions ,Monoclonal antibody ,SARS-CoV-2/immunology ,Article ,Antigenic drift ,Structure-Activity Relationship ,03 medical and health sciences ,Neutralization Tests ,Viral entry ,medicine ,Humans ,B.1.1.7 ,Spike Glycoprotein, Coronavirus/chemistry ,SARS-CoV-2 ,immune escape ,COVID-19 ,neutralization ,Antibodies, Neutralizing ,Virology ,030104 developmental biology ,Mutation ,biology.protein ,Cross Reactions/immunology - Abstract
Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants., Graphical abstract, The impact of mutations arising in SARS-CoV-2 Spike on antigenicity is still not known. Graham et al. isolate potent neutralizing monoclonal antibodies from individuals experiencing a range of COVID-19 disease severity that target RBD, NTD, and non-S1 epitopes. The B.1.1.7 variant of concern was most resistant to NTD-specific nAbs whereas RBD-specific nAbs retained potent neutralization.
- Published
- 2021
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