The molecular reach of antibodies crucially underpins their viral neutralisation capacity
Issued Date
2025-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85214001881
Pubmed ID
39746910
Journal Title
Nature Communications
Volume
16
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.16 No.1 (2025)
Suggested Citation
Huhn A., Nissley D., Wilson D.B., Kutuzov M.A., Donat R., Tan T.K., Zhang Y., Barton M.I., Liu C., Dejnirattisai W., Supasa P., Mongkolsapaya J., Townsend A., James W., Screaton G., van der Merwe P.A., Deane C.M., Isaacson S.A., Dushek O. The molecular reach of antibodies crucially underpins their viral neutralisation capacity. Nature Communications Vol.16 No.1 (2025). doi:10.1038/s41467-024-54916-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/102848
Title
The molecular reach of antibodies crucially underpins their viral neutralisation capacity
Corresponding Author(s)
Other Contributor(s)
Abstract
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.