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September 19, 2025Open Access

Prevalence of Resistance‐Associated Mutations in RSV F Protein Against Monoclonal Antibodies Prior to Widespread Implementation: Findings From a Prospective German Pediatric Cohort

MWMartin WetzkeMedizinische Hochschule Hannover DLDuyen Bao LeDüsseldorf University Hospital ITInga TomettenDüsseldorf University Hospital

Key Points

Prevalence of resistance-associated substitutions in RSV F protein was under 1% for all antibodies examined.
Sequencing of the RSV F protein was conducted on 1042 samples from German infants across two seasons.
Continued surveillance for resistance mutations in RSV remains necessary due to potential selection pressure.
Current escape-mutant infections pose a low risk, underscoring vigilance in monitoring RSV mutations.

Abstract

ABSTRACT Background The emergence of resistance‐associated substitutions in RSV against novel monoclonal antibodies is a concern given widespread prophylactic use. Aim To assess the prevalence of resistance‐associated substitutions in the RSV F protein against nirsevimab, clesrovimab, and palivizumab in German infants before widespread implementation of nirsevimab. Materials & Methods We sequenced the F protein of n = 1042 RSV samples from German infants from seasons 2021/2022 and 2022/2023 and screened for variants in binding sites for nirsevimab (Site Ø), clesrovimab (Site IV), and palivizumab (Site II). Results Prevalence of resistance‐associated substitutions was low (< 1%) for all three monoclonal antibodies. Conclusion Although the current risk of infections with escape‐mutants appears to be low, our results underline the need for continued surveillance, as resistance‐conferring mutations to new mAbs circulated and may be selected under selection pressure.

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