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呼吸道合胞病毒疫苗领域:从墓地中吸取的教训和有前途的候选者。

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates.

机构信息

Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands; Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, Netherlands.

Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA.

出版信息

Lancet Infect Dis. 2018 Oct;18(10):e295-e311. doi: 10.1016/S1473-3099(18)30292-5. Epub 2018 Jun 18.

Abstract

The global burden of disease caused by respiratory syncytial virus (RSV) is increasingly recognised, not only in infants, but also in older adults (aged ≥65 years). Advances in knowledge of the structural biology of the RSV surface fusion glycoprotein have revolutionised RSV vaccine development by providing a new target for preventive interventions. The RSV vaccine landscape has rapidly expanded to include 19 vaccine candidates and monoclonal antibodies (mAbs) in clinical trials, reflecting the urgency of reducing this global health problem and hence the prioritisation of RSV vaccine development. The candidates include mAbs and vaccines using four approaches: (1) particle-based, (2) live-attenuated or chimeric, (3) subunit, (4) vector-based. Late-phase RSV vaccine trial failures highlight gaps in knowledge regarding immunological protection and provide lessons for future development. In this Review, we highlight promising new approaches for RSV vaccine design and provide a comprehensive overview of RSV vaccine candidates and mAbs in clinical development to prevent one of the most common and severe infectious diseases in young children and older adults worldwide.

摘要

呼吸道合胞病毒(RSV)引起的疾病在全球范围内的负担日益加重,不仅在婴儿中,而且在老年人(年龄≥65 岁)中也是如此。对 RSV 表面融合糖蛋白结构生物学的认识的进步,通过为预防干预提供了新的目标,彻底改变了 RSV 疫苗的开发。RSV 疫苗领域迅速扩大,包括 19 种候选疫苗和临床试验中的单克隆抗体(mAb),这反映了减少这一全球健康问题的紧迫性,因此优先考虑 RSV 疫苗的开发。候选疫苗包括 mAb 和使用以下四种方法的疫苗:(1)基于颗粒的,(2)减毒或嵌合的,(3)亚单位的,(4)基于载体的。后期 RSV 疫苗试验的失败凸显了人们对免疫保护的认识存在差距,并为未来的发展提供了经验教训。在这篇综述中,我们强调了 RSV 疫苗设计的有前途的新方法,并全面概述了正在临床开发中用于预防全球最常见和最严重的传染病之一的 RSV 候选疫苗和 mAb。

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