A self-amplifying RNA vaccine prevents enterovirus D68 infection and disease in preclinical models

IF 15.8 1区 医学 Q1 CELL BIOLOGY Science Translational Medicine Pub Date : 2024-08-07 DOI:10.1126/scitranslmed.adi1625
Nikole L. Warner, Jacob Archer, Stephanie Park, Garima Singh, Kathryn M. McFadden, Taishi Kimura, Katrina Nicholes, Adrian Simpson, Jason T. Kaelber, David W. Hawman, Heinz Feldmann, Amit P. Khandhar, Peter Berglund, Matthew R. Vogt, Jesse H. Erasmus
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Abstract

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.
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自扩增 RNA 疫苗可在临床前模型中预防肠道病毒 D68 感染和疾病。
最近出现的严重急性呼吸系统综合症冠状病毒 2,通过原型病原体和疫苗平台方法得以快速应对,而 RNA 疫苗技术在相关的中东呼吸系统综合症冠状病毒中的抢先应用,则推动了这一进程。最近,美国国家过敏症和传染病研究所确定了九个值得关注的病毒家族,其中八个是包膜病毒家族,一个是无包膜病毒家族,疫苗的生产是这些病毒家族的当务之急。虽然针对各种包膜病毒的 RNA 疫苗已经问世,但针对非包膜病毒的 RNA 疫苗还缺乏路线图。肠道病毒 D68 最近被指定为非包膜病毒 Picornaviridae 科中的原型病原体,因为它进化迅速,传播途径为呼吸道,而且目前还缺乏多种抗肠道病毒疫苗的研发方法。在本文中,我们介绍了一种概念验证方法,该方法使用临床阶段的 RNA 疫苗平台,在小鼠和非人灵长类动物体内诱导出强大的肠道病毒 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,我们还利用我们的平台快速鉴定了肠道病毒 D68 六种基因型的抗原多样性,为指导多价疫苗的组成提供了必要的数据,这些多价疫苗能引起最佳广度的中和反应。这些结果表明,RNA 疫苗可以作为大流行准备工具箱中的工具,用于非包膜病毒。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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