Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford, UK.
Nat Commun. 2021 Aug 26;12(1):5125. doi: 10.1038/s41467-021-25265-4.
Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017-2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.
人类呼吸道合胞病毒（RSV）是全球婴幼儿下呼吸道感染的主要原因，但关于宿主内 RSV 多样性知之甚少。在这里，我们使用 2017 年至 2020 年期间收集的 319 份鼻咽拭子的深度测序数据，对宿主内 RSV 群体进行了特征描述。在群体水平上，与 RSV-A 相比，RSV-B 的共识多样性较低，但表现出更大的宿主内多样性。两种 RSV-B 共识序列在融合（F）蛋白中有一个氨基酸改变（K68N），这与降低对新型 RSV 单克隆抗体 nirsevimab（MEDI8897）的敏感性有关，该单克隆抗体正在开发中。此外，还在 F 蛋白的抗原位点鉴定出了几个次要变体，其中一个可能对 palivizumab 具有抗性，palivizumab 是唯一获得许可的 RSV 单克隆抗体。宿主内病毒群体的差异强调了监测疫苗效果的重要性，并可能有助于解释两种亚群之间单克隆抗体逃逸突变体的不同流行率。
