Office of Vaccines Research and Review, Center for Biologics Research and Review, US Food and Drug Administration, Silver Spring, MD, United States.
Office of Vaccines Research and Review, Center for Biologics Research and Review, US Food and Drug Administration, Silver Spring, MD, United States.
Vaccine. 2020 Jan 10;38(2):101-106. doi: 10.1016/j.vaccine.2019.10.048. Epub 2019 Nov 6.
Respiratory syncytial virus (RSV), is a common cause of serious acute lower respiratory tract illness in infants and young children, causing substantial morbidity and mortality globally. Treatment is mainly supportive and currently there is no licensed preventive vaccine. Clinical trials conducted in the 1960s evaluating a formalin-inactivated RSV vaccine (FI-RSV) in RSV-naïve infants resulted in observations of enhanced respiratory disease (ERD) following subsequent natural RSV infection in vaccinees. In these studies, infants immunized with FI-RSV had higher rates of severe RSV disease compared with controls. This outcome redirected focus on identifying the immunologic mechanisms that precipitated ERD as a prerequisite to further vaccine development. Improved understanding of the immunopathogenesis of ERD derived from animal models has stimulated development of new candidate vaccines and engendered discussions among RSV experts about the safety data needed to advance these products into the clinic, and ultimately, into the target population of RSV-naïve infants. The recognition that multiple products would soon be ready for testing in infants and children prompted the FDA to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting to seek perspectives and advice of experts regarding the types and extent of preclinical and clinical data that might be needed to support testing in RSV-naïve infants for specific types of candidate RSV vaccines. Committee members agreed that, if certain conditions are met in preclinical and early clinical studies, it would be reasonable to move forward from studies in adults and older children and into clinical trials evaluating vaccine safety and efficacy in RSV-naïve infants. Herein, we review and summarize perspectives on the discussion regarding recommendations for RSV vaccine development in this population.
呼吸道合胞病毒（RSV）是导致婴儿和幼儿严重急性下呼吸道疾病的常见原因，在全球范围内造成了大量发病率和死亡率。目前尚无批准的预防疫苗，治疗主要是支持性的。20 世纪 60 年代在 RSV 初免婴儿中进行的临床试验评估了一种福尔马林灭活 RSV 疫苗（FI-RSV），结果观察到疫苗接种者随后自然 RSV 感染后出现增强性呼吸道疾病（ERD）。在这些研究中，与对照组相比，接种 FI-RSV 的婴儿 RSV 严重疾病的发生率更高。这一结果将研究重点转移到确定引发 ERD 的免疫机制上，这是进一步开发疫苗的前提。从动物模型中对 ERD 的免疫发病机制的深入了解，刺激了新候选疫苗的开发，并促使 RSV 专家就推进这些产品进入临床、最终进入 RSV 初免婴儿这一目标人群所需的安全性数据展开讨论。认识到多种产品很快将准备好在婴儿和儿童中进行测试，促使 FDA 召开疫苗和相关生物制品咨询委员会（VRBPAC）会议，征求专家对可能需要支持 RSV 初免婴儿特定类型候选 RSV 疫苗测试的临床前和临床数据类型和范围的意见和建议。委员会成员一致认为，如果在临床前和早期临床试验中满足某些条件，从成人和大龄儿童的研究推进到评估 RSV 初免婴儿疫苗安全性和有效性的临床试验是合理的。在此，我们回顾和总结了关于该人群 RSV 疫苗开发建议讨论的观点。
