A replicating RNA vaccine protects cynomolgus macaques against lethal clade 2.3.4.4b influenza A H5N1 virus challenge

IF 14.6 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2025-10-08 DOI:10.1126/scitranslmed.adw4646

David W. Hawman, Amanda Griffin, Natalie McCarthy, Atsushi Okumura, Shanna S. Leventhal, Mahati Agumamidi, Michael Chorabik Jr., Ekaterina Altynova, Matthew Lewis, Troy Hinkley, E. Taylor Stone, Nikole Warner, Stephanie Park, Jamie Lovaglio, Brian J. Smith, Patrick Hanley, Greg Saturday, Carl Shaia, Chad Clancy, Kyle Rosenke, Jesse H. Erasmus, Heinz Feldmann

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引用次数: 0

Abstract

In early 2024, clade 2.3.4.4b highly pathogenic avian influenza (HPAI) A H5N1 virus was detected in United States dairy cattle. Although so far the public health threat of contemporary clade 2.3.4.4b H5N1 virus strains remains low, continued circulation in mammals and frequent spillover into humans poses a threat of pandemic H5N1. The United States and other countries have stockpiled vaccines and have plans in place to rapidly produce additional vaccine doses should a pandemic H5N1 virus emerge. However, the continued antigenic drift of clade 2.3.4.4b H5N1 antigens compared with historical antigens used by stockpiled vaccines has raised questions of whether these vaccines will confer protection or whether stockpiles need to be updated. We recently evaluated a replicating RNA (repRNA) vaccine against lethal contemporary 2.3.4.4b H5N1 virus challenge in mice and found that a homologous, but not historical, H5 hemagglutinin (HA)–based vaccine conferred protection. Here, we further evaluated the protective capacity of a repRNA expressing the contemporary 2.3.4.4b HA or a repRNA expressing a historical H5 HA (A/Vietnam/1203/2004) in a recently developed lethal nonhuman primate (NHP) challenge model. We found that both vaccines conferred robust protection against lethal 2.3.4.4b H5N1 virus challenge, reducing viral loads and signs of respiratory illness. Our data show that the repRNA platform can elicit protective immunity against lethal influenza virus challenge in NHPs and that historical H5 HAs can elicit cross-protective immunity.

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一种复制RNA疫苗保护食蟹猴免受致命进化枝2.3.4.4b甲型流感H5N1病毒的攻击

2024年初，在美国奶牛中发现了2.3.4.4b高致病性禽流感（HPAI） A型H5N1病毒。尽管到目前为止，现代进化支2.3.4.4b型H5N1病毒株对公共卫生的威胁仍然很低，但哺乳动物中的持续传播和频繁的向人类扩散构成了H5N1大流行的威胁。美国和其他国家已经储备了疫苗，并制定了计划，以便在出现H5N1大流行病毒时迅速生产更多的疫苗剂量。然而，与储存疫苗使用的历史抗原相比，2.3.4.4b进化支H5N1抗原的持续抗原漂移提出了这些疫苗是否具有保护作用或是否需要更新库存的问题。我们最近在小鼠身上评估了一种复制RNA （repRNA）疫苗对当代致命的2.3.4.4b H5N1病毒的攻击，发现一种同源的（但不是历史上的）基于H5血凝素（HA）的疫苗具有保护作用。在新建立的致死性非人灵长类动物（NHP）攻击模型中，我们进一步评估了表达当代2.3.4.4b HA的repRNA和表达历史H5 HA （a /Vietnam/1203/2004）的repRNA的保护能力。我们发现，这两种疫苗都对致命的2.3.4.4b H5N1病毒攻击具有强大的保护作用，减少了病毒载量和呼吸道疾病的迹象。我们的数据表明，repRNA平台可以在NHPs中引发对致命流感病毒攻击的保护性免疫，并且历史H5 HAs可以引发交叉保护性免疫。

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 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.