在两项 nirsevimab 随机临床试验中婴儿呼吸道合胞病毒感染的分子和表型特征。

Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials.

机构信息

Bioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

出版信息

Nat Commun. 2023 Jul 19;14(1):4347. doi: 10.1038/s41467-023-40057-8.

Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.

尼司他丁是一种单克隆抗体，可与呼吸道合胞病毒（RSV）融合蛋白结合。在 2b 期临床试验（NCT02878330）和 MELODY 临床试验（NCT03979313）中，婴儿在首次 RSV 季节前接受一剂尼司他丁或安慰剂。在这项预先指定的分析中，从 RSV 感染中分离出的病毒进行了亚型分型、测序，并分析了尼司他丁结合位点的取代；随后，对重组 RSV 进行了微量中和敏感性测试。在此我们表明，两种试验中 A 型和 B 型的感染频率相似。此外，RSV A 有一个融合蛋白取代，而 RSV B 有 10 个融合蛋白取代，其频率>5%。值得注意的是，除了高度流行的 I206M：Q209R 外，RSV B 的结合位点取代很少，该取代增加了尼司他丁的敏感性；两名参与者的 RSV B 分离株具有降低尼司他丁敏感性的结合位点取代。总体而言，来自 2b 期临床试验和 MELODY 临床试验的>99%的分离株对尼司他丁保持敏感性。