Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.
PATH, Center for Vaccine Innovation & Access, Seattle, WA, USA.
Lancet Infect Dis. 2023 Jan;23(1):e2-e21. doi: 10.1016/S1473-3099(22)00291-2. Epub 2022 Aug 8.
Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralising antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. An extended half-life monoclonal antibody for all infants is likely to be within 1 year of regulatory approval (from August, 2022) for high-income countries. Live-attenuated vaccines are in development for older infants (aged >6 months). Subunit vaccines are in late-stage trials for pregnant women to protect infants, whereas vector, subunit, and nucleic acid approaches are being developed for older adults. Urgent next steps include ensuring access and affordability of a respiratory syncytial virus vaccine globally. This review gives an overview of respiratory syncytial virus vaccines and monoclonal antibodies in clinical development highlighting different target populations, antigens, and trial results.
呼吸道合胞病毒是导致婴儿死亡的第二大常见原因,也是导致老年人(年龄大于 60 岁)发病率和死亡率的主要原因。开发呼吸道合胞病毒疫苗或免疫预防的努力仍然非常活跃。目前有 33 种呼吸道合胞病毒预防候选物正在使用六种不同方法进行临床开发:重组载体、亚单位、基于颗粒、减毒活疫苗、嵌合和核酸疫苗;以及单克隆抗体。有 9 种候选物正在进行 3 期临床试验。了解高度中和抗体的表位,导致疫苗和单克隆抗体设计从经验主义转变为理性和基于结构。一种延长半衰期的单克隆抗体,用于所有婴儿,可能在监管批准(2022 年 8 月)后 1 年内用于高收入国家。正在为年龄较大的婴儿(年龄大于 6 个月)开发减毒活疫苗。正在进行亚单位疫苗的后期试验,以保护孕妇所生婴儿,而载体、亚单位和核酸方法正在为老年人开发。下一步的当务之急是确保呼吸道合胞病毒疫苗在全球范围内的可及性和可负担性。本综述概述了呼吸道合胞病毒疫苗和单克隆抗体的临床开发情况,重点介绍了不同的目标人群、抗原和试验结果。