尼尔塞维马布突破性感染后呼吸道同胞病毒的基因型和表型表征:一个大型的,多中心的,观察性,现实世界的研究
Slim Fourati1, Alawiya Reslan2, Jérome Bourret3
1Department of Virology, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France; Université Paris-Est-Créteil, Créteil, France; INSERM U955, Team Viruses, Hepatology, Cancer, Créteil, France.
The Lancet. Infectious diseases
|October 17, 2024
概括
尼尔西维玛是有效的预防呼吸道同胞病毒 (RSV) 在婴儿. 虽然nirsevimab突破性感染很少见,但分子监测对于检测潜在的RSV逃生变体至关重要,特别是在RSV-B菌株中.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 公共卫生 公共卫生
背景情况:
- 长效单克隆抗体Nirsevimab已被批准用于预防婴儿呼吸道同胞病毒 (RSV) 感染.
- 在法国 (2023-24赛季) 广泛使用nirsevimab引发了人们对潜在的RSV逃生变体选择和传播的担忧.
- 从突破性感染中鉴别RSV对于评估nirsevimab的疗效和监测病毒演变至关重要.
研究的目的:
- 描述与婴儿内尼尔塞维马布突破性感染相关的呼吸道同胞性病毒 (RSV).
- 为了研究RSV菌株的遗传和表型性质,在尼尔塞维玛布给药后.
- 评估循环RSV中与nirsevimab耐药性相关的替代物的流行率.
主要方法:
- 在2023-24年RSV季节,法国进行了一项多中心,全国性的观察性研究.
- 在患有突破性感染的婴儿的呼吸道样本上进行了全长RSVRNA测序.
- 临床RSV分离物被测试为nirsevimab中和和F蛋白替代物被分析通过融合抑制试验.
主要成果:
- 从突破性感染中测序的545个RSV基因组中,260个来自尼尔塞维马布治疗的婴儿 (91%RSV-A,9%RSV-B).
- 在RSV-A株中没有发现与nirsevimab耐药性相关的替代物.
- 两个RSV-B菌株 (8%) 呈现出与耐药性相关的替代物 (F:N208D和F:I64M加F:K65R),在体外显示出高耐尼尔塞维马布耐药性.
结论:
- 尼尔塞维马布突破性变体很少见,即使广泛使用,也表明药物的持续有效性.
- 在RSV-B中识别了与耐药性相关的替代体,这凸显了持续分子监测的必要性.
- 这项研究代表了迄今为止Nirsevimab突破性感染的最大的基因型和表型监测.
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