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bioRxiv · 10.1101/2025.01.04.631317

Structural basis for postfusion-specific binding to Respiratory Syncytial Virus F protein by the canonical antigenic site I antibody 131-2a

Peng, W.·Siborova, M.·Wu, X.·Du, W.·Schulte, D.·Pronker, M. F.·de Haan, C. A. M.·Snijder, J.
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Abstract

The Respiratory Syncytial Virus (RSV) Fusion (F) protein is a major target of antiviral antibodies following natural infection or vaccination and responsible for mediating fusion between the viral envelope and the host membrane. The fusion process is driven by a large-scale conformational change in F, switching irreversibly from the metastable prefusion state to the stable postfusion conformation. Previous research has identified six distinct antigenic sites in RSV-F, termed sites O, I, II, III, IV, and V. Of these, only antigenic site I is fully specific to the postfusion conformation of F. A monoclonal antibody 131-2a that specifically targets postfusion F has been widely used as a research tool to probe for postfusion F and to define antigenic site I in serological studies, yet its sequence and precise epitope have remained unknown. Here we use mass spectrometry-based de novo sequencing of 131-2a to reverse engineer a recombinant product and study the epitope to define antigenic site I with molecular detail, revealing the structural basis for the antibodys specificity towards postfusion RSV-F.

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Peng, W., Siborova, M., Wu, X., Du, W., Schulte, D., Pronker, M. F., de Haan, C. A. M., Snijder, J.. 2025-01-04. Structural basis for postfusion-specific binding to Respiratory Syncytial Virus F protein by the canonical antigenic site I antibody 131-2a. https://doi.org/10.1101/2025.01.04.631317

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