The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. The Modified Vaccinia Ankara (MVA) vector system is being explored as a platform for development of multiple vaccines. This paper reviews the molecular and biological features specifically of the MVA-BN vector system, followed by a template with details on the safety and characteristics of an MVA-BN based vaccine against Zaire ebolavirus and other filovirus strains. The MVA-BN-Filo vaccine is based on a live, highly attenuated poxviral vector incapable of replicating in human cells and encodes glycoproteins of Ebola virus Zaire, Sudan virus and Marburg virus and the nucleoprotein of the Thai Forest virus. This vaccine has been approved in the European Union in July 2020 as part of a heterologous Ebola vaccination regimen. The MVA-BN vector is attenuated following over 500 serial passages in eggs, showing restricted host tropism and incompetence to replicate in human cells. MVA has six major deletions and other mutations of genes outside these deletions, which all contribute to the replication deficiency in human and other mammalian cells. Attenuation of MVA-BN was demonstrated by safe administration in immunocompromised mice and non-human primates. In multiple clinical trials with the MVA-BN backbone, more than 7800 participants have been vaccinated, demonstrating a safety profile consistent with other licensed, modern vaccines. MVA-BN has been approved as smallpox vaccine in Europe and Canada in 2013, and as smallpox and monkeypox vaccine in the US in 2019. No signal for inflammatory cardiac disorders was identified throughout the MVA-BN development program. This is in sharp contrast to the older, replicating vaccinia smallpox vaccines, which have a known risk for myocarditis and/or pericarditis in up to 1 in 200 vaccinees. MVA-BN-Filo as part of a heterologous Ebola vaccination regimen (Ad26.ZEBOV/MVA-BN-Filo) has undergone clinical testing including Phase III in West Africa and is currently in use in large scale vaccination studies in Central African countries. This paper provides a comprehensive picture of the MVA-BN vector, which has reached regulatory approvals, both as MVA-BN backbone for smallpox/monkeypox, as well as for the MVA-BN-Filo construct as part of an Ebola vaccination regimen, and therefore aims to provide solutions to prevent disease from high-consequence human pathogens.

布莱顿合作病毒载体疫苗安全工作组 (V3SWG) 的成立是为了评估重组活病毒载体疫苗的安全性和特性。改良安卡拉牛痘 (MVA) 载体系统正在探索作为多种疫苗开发的平台。本文特别回顾了 MVA-BN 载体系统的分子和生物学特征，随后提供了一个模板，其中详细介绍了针对扎伊尔埃博拉病毒和其他丝状病毒株的基于 MVA-BN 的疫苗的安全性和特性。 MVA-BN-Filo 疫苗基于高度减毒的活痘病毒载体，无法在人体细胞中复制，编码埃博拉病毒扎伊尔病毒、苏丹病毒和马尔堡病毒的糖蛋白以及泰国森林病毒的核蛋白。该疫苗已于 2020 年 7 月在欧盟获得批准，作为异源埃博拉疫苗接种方案的一部分。 MVA-BN 载体在卵中连续传代 500 多次后减弱，显示出宿主向性受限且无法在人类细胞中复制。 MVA 有 6 个主要缺失以及这些缺失之外的其他基因突变，这些都导致人类和其他哺乳动物细胞的复制缺陷。通过对免疫功能低下的小鼠和非人灵长类动物进行安全给药，证明了 MVA-BN 的减毒作用。在 MVA-BN 骨干的多项临床试验中，超过 7800 名参与者已接种疫苗，证明其安全性与其他获得许可的现代疫苗一致。 MVA-BN 已于 2013 年在欧洲和加拿大被批准作为天花疫苗，并于 2019 年在美国被批准作为天花和猴痘疫苗。在整个 MVA-BN 开发计划中没有发现炎症性心脏病的信号。 这与较旧的复制型牛痘天花疫苗形成鲜明对比，后者已知高达二百分之一的疫苗接种者有患心肌炎和/或心包炎的风险。 MVA-BN-Filo 作为异源埃博拉疫苗接种方案 (Ad26.ZEBOV/MVA-BN-Filo) 的一部分，已在西非进行了包括 III 期在内的临床测试，目前正用于中非国家的大规模疫苗接种研究。本文提供了 MVA-BN 载体的全面介绍，该载体已获得监管部门的批准，既可作为天花/猴痘的 MVA-BN 主干，也可用于作为埃博拉疫苗接种方案一部分的 MVA-BN-Filo 构建体，以及因此，旨在提供解决方案来预防高后果人类病原体引起的疾病。