Vaccine Research Center, National Institutes of Health, Bethesda, MD, United States.
Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, United States.
Front Immunol. 2019 Jul 25;10:1675. doi: 10.3389/fimmu.2019.01675. eCollection 2019.
Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in young children and a substantial contributor to respiratory tract disease throughout life and as such a high priority for vaccine development. However, after nearly 60 years of research no vaccine is yet available. The challenges to developing an RSV vaccine include the young age, 2-4 months of age, for the peak of disease, the enhanced RSV disease associated with the first RSV vaccine, formalin-inactivated RSV with an alum adjuvant (FI-RSV), and difficulty achieving protection as illustrated by repeat infections with disease that occur throughout life. Understanding the biology of infection and disease pathogenesis has and will continue to guide vaccine development. In this paper, we review the roles that RSV proteins play in the biology of infection and disease pathogenesis and the corresponding contribution to live attenuated and subunit RSV vaccines. Each of RSV's 11 proteins are in the design of one or more vaccines. The G protein's contribution to disease pathogenesis through altering host immune responses as well as its role in the biology of infection suggest it can make a unique contribution to an RSV vaccine, both live attenuated and subunit vaccines. One of G's potential unique contributions to a vaccine is the potential for anti-G immunity to have an anti-inflammatory effect independent of virus replication. Though an anti-viral effect is essential to an effective RSV vaccine, it is important to remember that the goal of a vaccine is to prevent disease. Thus, other effects of the infection, such as G's alteration of the host immune response may provide opportunities to induce responses that block this effect and improve an RSV vaccine. Keeping in mind the goal of a vaccine is to prevent disease and not virus replication may help identify new strategies for other vaccine challenges, such as improving influenza vaccines and developing HIV vaccines.
呼吸道合胞病毒（RSV）是导致婴幼儿严重下呼吸道疾病的主要原因，也是导致整个生命周期呼吸道疾病的主要原因，因此是疫苗开发的重中之重。然而，经过近 60 年的研究，仍然没有疫苗问世。开发 RSV 疫苗的挑战包括疾病高峰期的年龄较小（2-4 个月）、与第一个 RSV 疫苗（福尔马林灭活 RSV 与铝佐剂（FI-RSV））相关的增强型 RSV 疾病以及难以实现保护，这体现在一生中会重复感染导致疾病。对感染和疾病发病机制的生物学理解一直并将继续指导疫苗的开发。在本文中，我们回顾了 RSV 蛋白在感染和疾病发病机制中的生物学作用及其对活减毒和亚单位 RSV 疫苗的相应贡献。RSV 的 11 种蛋白中的每一种都参与了一种或多种疫苗的设计。G 蛋白通过改变宿主免疫反应以及其在感染生物学中的作用在疾病发病机制中的作用表明，它可以为 RSV 疫苗，无论是活减毒疫苗还是亚单位疫苗，做出独特的贡献。G 蛋白对疫苗的潜在独特贡献之一是抗 G 免疫可能具有独立于病毒复制的抗炎作用。尽管抗病毒作用对于有效的 RSV 疫苗至关重要，但重要的是要记住疫苗的目的是预防疾病。因此，感染的其他影响，如 G 改变宿主免疫反应，可能为诱导阻断这种作用的反应并改善 RSV 疫苗提供机会。记住疫苗的目的是预防疾病而不是病毒复制，这可能有助于确定其他疫苗挑战的新策略，例如改进流感疫苗和开发 HIV 疫苗。
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