Lamichhane Binit, Minney-Smith Cara A, Gazeley Jake, Wadia Ushma, Foley David A, Moore Hannah C, Maticevic Jelena, Smith David W, Effler Paul, Blyth Christopher C, Speers David, Levy Avram
Department of Microbiology, PathWest Laboratory Medicine WA, Nedlands, Australia.
School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia.
Open Forum Infect Dis. 2025 Jul 18;12(8):ofaf429. doi: 10.1093/ofid/ofaf429. eCollection 2025 Aug.
Nirsevimab is a long-acting monoclonal antibody used to prevent respiratory syncytial virus (RSV) infection in infants and high-risk children. During the 2024 RSV season in Western Australia, 21 922 doses were administered to infants entering their first season and 1221 doses to at-risk children. In this context, the selection and spread of escape variants are a potential concern. This study aimed to investigate nirsevimab binding site mutations using clinical and wastewater data.
We performed whole genome sequencing on 382 clinical RSV samples and 12 wastewater samples collected between September 2023 and October 2024. RSV subtypes, genetic diversity, and mutations within the nirsevimab binding region of the F protein were analyzed. Phylogenetic analysis was conducted to assess lineage dynamics and the potential emergence of escape variants.
RSV-A was the dominant subtype (61.8%), with RSV-B accounting for 38.2% of cases. No lineage shifts were observed following nirsevimab introduction, and none of the known mutations associated with high-level nirsevimab resistance were detected in either clinical or wastewater samples. The prevalent RSV-B mutation combination (F:I206M:Q209R:S211N) was observed consistently but is not associated with reduced nirsevimab efficacy. Wastewater sampling, covering approximately 2 million people from the Perth metropolitan region, confirmed findings from clinical sequences, reinforcing the absence of resistance mutations.
No evidence of nirsevimab escape mutations was found in clinical or wastewater samples during the 2024 RSV season. Continued genomic surveillance, including wastewater monitoring, is essential to detect emerging resistance and ensure the long-term efficacy of prophylactic interventions.
尼塞维单抗是一种长效单克隆抗体，用于预防婴儿和高危儿童的呼吸道合胞病毒（RSV）感染。在西澳大利亚州2024年RSV流行季期间，为进入首个流行季的婴儿接种了21922剂，为高危儿童接种了1221剂。在此背景下，逃逸变异株的选择和传播是一个潜在问题。本研究旨在利用临床和废水数据调查尼塞维单抗结合位点突变情况。
我们对2023年9月至2024年10月期间收集的382份临床RSV样本和12份废水样本进行了全基因组测序。分析了RSV亚型、遗传多样性以及F蛋白尼塞维单抗结合区域内的突变情况。进行系统发育分析以评估谱系动态和逃逸变异株的潜在出现情况。
RSV-A是主要亚型（61.8%），RSV-B占病例的38.2%。引入尼塞维单抗后未观察到谱系转变，临床或废水样本中均未检测到与高水平尼塞维单抗耐药相关的已知突变。一致观察到普遍存在的RSV-B突变组合（F:I206M:Q209R:S211N），但该组合与尼塞维单抗疗效降低无关。覆盖珀斯大都市区约200万人的废水采样证实了临床序列的结果，进一步证明不存在耐药突变。
在2024年RSV流行季期间，临床或废水样本中未发现尼塞维单抗逃逸突变的证据。持续的基因组监测，包括废水监测，对于检测新出现的耐药性并确保预防性干预措施的长期疗效至关重要。
