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The molecular reach of antibodies crucially underpins their viral neutralisation capacity
by
Townsend, Alain
, Dushek, Omer
, Tan, Tiong Kit
, Supasa, Piyada
, Huhn, Anna
, Kutuzov, Mikhail A.
, Dejnirattisai, Wanwisa
, Isaacson, Samuel A.
, Donat, Robert
, Barton, Michael I.
, Nissley, Daniel
, Screaton, Gavin
, Deane, Charlotte M.
, Zhang, Ying
, van der Merwe, P. Anton
, Wilson, Daniel B.
, James, William
, Liu, Chang
, Mongkolsapaya, Juthathip
in
631/1647/1888/2005
/ 631/250/2152/2153/1291
/ Affinity
/ Antibodies
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Antibody Affinity
/ Antigens
/ Antigens, Viral - immunology
/ Binding
/ Bispecific antibodies
/ Correlation
/ COVID-19 - immunology
/ COVID-19 - virology
/ Epitopes
/ Epitopes - immunology
/ Humanities and Social Sciences
/ Humans
/ Immunoglobulin G
/ Immunoglobulin G - immunology
/ Immunoglobulin G - metabolism
/ Kinetics
/ Medical research
/ multidisciplinary
/ Parameters
/ Protein Binding
/ SARS-CoV-2 - immunology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike Glycoprotein, Coronavirus - metabolism
2025
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The molecular reach of antibodies crucially underpins their viral neutralisation capacity
by
Townsend, Alain
, Dushek, Omer
, Tan, Tiong Kit
, Supasa, Piyada
, Huhn, Anna
, Kutuzov, Mikhail A.
, Dejnirattisai, Wanwisa
, Isaacson, Samuel A.
, Donat, Robert
, Barton, Michael I.
, Nissley, Daniel
, Screaton, Gavin
, Deane, Charlotte M.
, Zhang, Ying
, van der Merwe, P. Anton
, Wilson, Daniel B.
, James, William
, Liu, Chang
, Mongkolsapaya, Juthathip
in
631/1647/1888/2005
/ 631/250/2152/2153/1291
/ Affinity
/ Antibodies
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Antibody Affinity
/ Antigens
/ Antigens, Viral - immunology
/ Binding
/ Bispecific antibodies
/ Correlation
/ COVID-19 - immunology
/ COVID-19 - virology
/ Epitopes
/ Epitopes - immunology
/ Humanities and Social Sciences
/ Humans
/ Immunoglobulin G
/ Immunoglobulin G - immunology
/ Immunoglobulin G - metabolism
/ Kinetics
/ Medical research
/ multidisciplinary
/ Parameters
/ Protein Binding
/ SARS-CoV-2 - immunology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike Glycoprotein, Coronavirus - metabolism
2025
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The molecular reach of antibodies crucially underpins their viral neutralisation capacity
by
Townsend, Alain
, Dushek, Omer
, Tan, Tiong Kit
, Supasa, Piyada
, Huhn, Anna
, Kutuzov, Mikhail A.
, Dejnirattisai, Wanwisa
, Isaacson, Samuel A.
, Donat, Robert
, Barton, Michael I.
, Nissley, Daniel
, Screaton, Gavin
, Deane, Charlotte M.
, Zhang, Ying
, van der Merwe, P. Anton
, Wilson, Daniel B.
, James, William
, Liu, Chang
, Mongkolsapaya, Juthathip
in
631/1647/1888/2005
/ 631/250/2152/2153/1291
/ Affinity
/ Antibodies
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Antibody Affinity
/ Antigens
/ Antigens, Viral - immunology
/ Binding
/ Bispecific antibodies
/ Correlation
/ COVID-19 - immunology
/ COVID-19 - virology
/ Epitopes
/ Epitopes - immunology
/ Humanities and Social Sciences
/ Humans
/ Immunoglobulin G
/ Immunoglobulin G - immunology
/ Immunoglobulin G - metabolism
/ Kinetics
/ Medical research
/ multidisciplinary
/ Parameters
/ Protein Binding
/ SARS-CoV-2 - immunology
/ Science
/ Science (multidisciplinary)
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike Glycoprotein, Coronavirus - metabolism
2025
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The molecular reach of antibodies crucially underpins their viral neutralisation capacity
Journal Article
The molecular reach of antibodies crucially underpins their viral neutralisation capacity
2025
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Overview
Key functions of antibodies, such as viral neutralisation, depend on high-affinity binding. However, viral neutralisation poorly correlates with antigen affinity for reasons that have been unclear. Here, we use a new mechanistic model of bivalent binding to study >45 patient-isolated IgG1 antibodies interacting with SARS-CoV-2 RBD surfaces. The model provides the standard monovalent affinity/kinetics and new bivalent parameters, including the molecular reach: the maximum antigen separation enabling bivalent binding. We find large variations in these parameters across antibodies, including reach variations (22–46 nm) that exceed the physical antibody size (~15 nm). By using antigens of different physical sizes, we show that these large molecular reaches are the result of both the antibody and antigen sizes. Although viral neutralisation correlates poorly with affinity, a striking correlation is observed with molecular reach. Indeed, the molecular reach explains differences in neutralisation for antibodies binding with the same affinity to the same RBD-epitope. Thus, antibodies within an isotype class binding the same antigen can display differences in molecular reach, substantially modulating their binding and functional properties.
Researchers developed an accurate model to analyse bivalent antibody binding. By analysing many SARS-CoV-2-specific antibodies, they found that their molecular reach can predict their neutralisation potency.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Affinity
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - chemistry
/ Antibodies, Viral - immunology
/ Antigens
/ Antigens, Viral - immunology
/ Binding
/ Epitopes
/ Humanities and Social Sciences
/ Humans
/ Immunoglobulin G - immunology
/ Immunoglobulin G - metabolism
/ Kinetics
/ Science
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - chemistry
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