Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto M5S 1A8, Ontario, Canada.
J Antimicrob Chemother. 2023 May 3;78(5):1143-1149. doi: 10.1093/jac/dkad076.
Respiratory syncytial virus (RSV) is a leading cause of hospitalization and infant mortality worldwide. There are currently no approved vaccines against RSV, and immunoprophylaxis with the mAb palivizumab is limited to extremely vulnerable infants in resource-rich settings due to its high cost and the need for monthly injections throughout the RSV season. Nirsevimab (formerly MEDI8897) is a highly potent, long-acting, human, recombinant mAb that received approval for the prevention of RSV infection in newborns and infants during their first RSV season from the EMA and the UK's Medicines and Healthcare products Regulatory Agency in November 2022 based on positive results in Phase 2b and 3 clinical trials. Nirsevimab targets the highly conserved site Ø of the prefusion conformation of the RSV fusion (F) protein and contains a triple amino acid substitution in the Fc domain that extends its half-life, allowing for a single dose to cover a typical RSV season in regions with temperate climates. In this article I review key attributes of nirsevimab with an emphasis on pharmacology, pharmacokinetics, antiviral activity, and the potential for resistance and escape variants. I also summarize current progress in clinical trials and consider future research priorities.
呼吸道合胞病毒（RSV）是全球导致住院和婴儿死亡的主要原因。目前尚无针对 RSV 的批准疫苗，由于其成本高且需要在 RSV 季节每月注射，因此使用 mAb 帕利珠单抗进行免疫预防仅限于资源丰富环境中极其脆弱的婴儿。Nirsevimab（前身为 MEDI8897）是一种高效、长效、人源、重组 mAb，于 2022 年 11 月，基于 2b 期和 3 期临床试验的积极结果，获得了 EMA 和英国药品和保健产品监管局批准，用于预防新生儿和婴儿在其首个 RSV 季节的 RSV 感染。Nirsevimab 靶向 RSV 融合（F）蛋白预融合构象的高度保守位点Ø，并在 Fc 结构域中包含三个氨基酸替换，延长了其半衰期，使其能够在温带地区覆盖典型的 RSV 季节只需一剂。本文重点介绍了 nirsevimab 的关键属性，包括药理学、药代动力学、抗病毒活性以及耐药性和逃逸变异的潜力。还总结了目前临床试验的进展，并考虑了未来的研究重点。
