The recent emergence and rapid response to severe acute respiratory syndrome coronavirus 2 was enabled by prototype pathogen and vaccine platform approaches, driven by the preemptive application of RNA vaccine technology to the related Middle East respiratory syndrome coronavirus. Recently, the National Institutes of Allergy and Infectious Diseases identified nine virus families of concern, eight enveloped virus families and one nonenveloped virus family, for which vaccine generation is a priority. Although RNA vaccines have been described for a variety of enveloped viruses, a roadmap for their use against nonenveloped viruses is lacking. Enterovirus D68 was recently designated a prototype pathogen within the family Picornaviridae of nonenveloped viruses because of its rapid evolution and respiratory route of transmission, coupled with a lack of diverse anti-enterovirus vaccine approaches in development. Here, we describe a proof-of-concept approach using a clinical stage RNA vaccine platform that induced robust enterovirus D68–neutralizing antibody responses in mice and nonhuman primates and prevented upper and lower respiratory tract infections and neurological disease in mice. In addition, we used our platform to rapidly characterize the antigenic diversity within the six genotypes of enterovirus D68, providing the necessary data to inform multivalent vaccine compositions that can elicit optimal breadth of neutralizing responses. These results demonstrate that RNA vaccines can be used as tools in our pandemic-preparedness toolbox for nonenveloped viruses.

中文翻译：

---

自扩增 RNA 疫苗在临床前模型中预防肠道病毒 D68 感染和疾病


最近对严重急性呼吸系统综合症冠状病毒 2 的出现和快速反应是通过原型病原体和疫苗平台方法实现的，这是由 RNA 疫苗技术先发制人地应用于相关的中东呼吸系统综合症冠状病毒所推动的。最近，美国国家过敏和传染病研究所确定了 9 个值得关注的病毒家族、8 个包膜病毒家族和 1 个无包膜病毒家族，疫苗生成是优先事项。尽管已经描述了针对各种包膜病毒的 RNA 疫苗，但缺乏用于非包膜病毒的路线图。肠道病毒 D68 最近被指定为非包膜病毒小核糖病毒科的原型病原体，因为它的快速进化和呼吸道传播途径，再加上缺乏多种正在开发的抗肠道病毒疫苗方法。在这里，我们描述了一种使用临床阶段 RNA 疫苗平台的概念验证方法，该方法在小鼠和非人灵长类动物中诱导了强大的肠道病毒 D68 中和抗体反应，并预防了小鼠的上下呼吸道感染和神经系统疾病。此外，我们使用我们的平台快速表征了肠道病毒 D68 的六种基因型中的抗原多样性，提供了必要的数据来告知可以引发最佳中和反应广度的多价疫苗组合物。这些结果表明，RNA 疫苗可以用作我们针对无包膜病毒的大流行准备工具箱中的工具。