Mutational constraints on RSV F and its neutralization by antibodies

Our study led by Cassie Simonich that characterizes how mutations to RSV F affect monoclonal antibodies was just published in Nature. This paper uses pseudovirus deep mutational scanning to measure how all F mutations affect clinical antibodies nirsevimab and clesrovimab, and provides a biophysical model that explains why escape from nirsevimab is more commonly observed in subtype B than A.

Antibodies against RSV have dramatically reduced infant hospitalizations in the United States. But resistance is a concern that needs to be monitored. In this study, Cassie used pseudovirus deep mutational scanning to measure how all mutations to F affect neutralization by current clinical antibodies as well as past antibodies and new ones in clinical development.

She also showed how nirsevimab has reduced Fab potency to RSV subtype B, and how this explains the greater rate of resistance in that subtype.

To access and view the deep mutational scanning data, see https://dms-vep.org/RSV_Long_F_DMS/.

To see a Nexstrain tree that uses the data to score current sequences for their antibody escape, see here.

For more explanation about the biophysical model, see here.

For some slides about this project, see https://slides.com/jbloom/grc-2026.