RSV F mutation map links antibody escape to subtype differences and real-time surveillance
Researchers combine a biophysical model of IgG/Bivalent binding with deep-mutational scanning of RSV F to quantify how virtually every single amino-acid mutation affects viral entry and neutralization by nirsevimab, clesrovimab, and other antibodies. They show that bivalent IgG buffering reduces the impact of mutations when Fab affinity is high, explaining why nirsevimab escape is more common in RSV-B than RSV-A, and validate many mutations across subtypes with pseudoviruses. The team then builds a real-time surveillance framework (escape scores integrated into Nextstrain/Pathoplexus) to monitor natural RSV sequences for resistance, finding resistant strains to be rare but present. They also profile historical/candidate antibodies (e.g., suptavumab, RSM01, 1A2, 1B6, palivizumab) and discuss implications for designing antibody therapies resilient to viral escape and for ongoing public-health surveillance.