Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center.
Division of Allergy and Infectious Disease, Department of Medicine, University of Washington.
Curr Opin Infect Dis. 2022 Aug 1;35(4):280-287. doi: 10.1097/QCO.0000000000000846. Epub 2022 Jul 5.
Monoclonal antibody (mAb) administration represents an important strategy for preventing and treating respiratory viral infections in vulnerable populations, including immunocompromised individuals. The purpose of this review is to provide an overview of mAbs in clinical use against respiratory viruses, highlight factors that modulate mAb clinical efficacy, and provide a perspective on future innovations in the field. This review focuses on publications from the last year.
Historically, clinical development of a single mAb has taken over a decade. The COVID-19 pandemic has demonstrated that this timeframe can be reduced to less than a year and has catalyzed rapid innovations in the field. Several novel mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization by the Food and Drug Administration (FDA) for the early treatment of mild to moderate COVID-19. However, the majority of these mAbs have ultimately failed due to the emergence of variants, highlighting an important lesson about predicting and countering resistance. Novel mAbs are also in clinical use or in late-stage development for the prevention of infection by SARS-CoV-2 and respiratory syncytial virus (RSV) in vulnerable populations. Several factors can be modulated to improve the clinical efficacy of mAbs. For example, Fc modifications can extend mAb half-life and increase respiratory tract bioavailability, both of which are attractive properties for achieving protection against respiratory viruses.
The mAb landscape is rapidly evolving with numerous examples of success and failure. The armamentarium of clinically-available mAbs to protect vulnerable populations is expected to undergo continued growth.
单克隆抗体（mAb）的应用是预防和治疗包括免疫功能低下者在内的易感染人群呼吸道病毒感染的重要策略。本综述旨在概述临床应用于呼吸道病毒的 mAb，强调调节 mAb 临床疗效的因素，并展望该领域的未来创新。本综述重点关注去年的出版物。
从历史上看，单一 mAb 的临床开发需要超过十年的时间。COVID-19 大流行表明，这一时间框架可以缩短至不到一年，并促进了该领域的快速创新。几种针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的新型 mAb 已获得美国食品和药物管理局（FDA）的紧急使用授权，用于治疗 COVID-19 的轻症和中度病例。然而，由于变种的出现，这些 mAb 中的大多数最终都失败了，这突显了关于预测和对抗耐药性的重要教训。新型 mAb 也正在临床应用或处于后期开发阶段，用于预防 SARS-CoV-2 和呼吸道合胞病毒（RSV）在易感染人群中的感染。有许多因素可以调节以提高 mAb 的临床疗效。例如，Fc 修饰可以延长 mAb 的半衰期并增加呼吸道的生物利用度，这两者都是实现呼吸道病毒保护的理想特性。
mAb 领域正在迅速发展，成功和失败的例子比比皆是。用于保护弱势群体的临床可用 mAb 武器库预计将继续增长。
