Prevalence of Resistance‐Associated Mutations in RSV F Protein Against Monoclonal Antibodies Prior to Widespread Implementation: Findings From a Prospective German Pediatric Cohort
Martin Wetzke, Duyen Bao Le, Inga Tometten, Simon Ritter, Nadine Lübke, Jörg Timm, Alexander Dilthey, Marcus Panning, Andreas Walker, Christine Happle
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.