IF 15.8 1区 医学 Q1 CELL BIOLOGY
Masato Hatta, Yasuko Hatta, Angela Choi, Jaber Hossain, Chenchen Feng, Matthew W. Keller, Jana M. Ritter, Ying Huang, Emma Fang, Elizabeth A. Pusch, Thomas Rowe, Juan A. De La Cruz, Monique C. Johnson, Jimma Liddell, Nannan Jiang, Daniel Stadlbauer, Li Liu, Arindam K. Bhattacharjee, Joseph R. Rouse, Michael Currier, Li Wang, Min Z. Levine, Marie K. Kirby, John Steel, Han Di, John R. Barnes, Carole Henry, C. Todd Davis, Raffael Nachbagauer, David E. Wentworth, Bin Zhou
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摘要

高致病性禽流感(HPAI)甲型 H5N1 病毒在全球范围内的传播构成了严重的大流行威胁,因此有必要迅速开发出有效的疫苗。信使核糖核酸(mRNA)疫苗技术在 COVID-19 大流行中的成功,以其快速开发和可扩展性为标志,证明了它在应对甲型 H5N1 高致病性禽流感等其他传染病威胁方面的潜力。因此,我们评估了针对泛发型甲型 H5 流感 2.3.4.4b 支系病毒的 mRNA 候选疫苗,这些病毒已被证明可感染一系列哺乳动物物种,包括最近在奶牛中检测到的病毒。给雪貂注射了由世界卫生组织推荐的 2.3.4.4b 原型疫苗病毒衍生出的单独编码血凝素或血凝素和神经氨酸酶的 mRNA 疫苗。评估了免疫反应的动力学以及对致命剂量 A(H5N1)病毒挑战的保护作用。接种两剂 mRNA 疫苗可针对 2022 年禽类分离株和 2024 年人类分离株产生强效中和抗体滴度。此外,接种 mRNA 疫苗还能保护雪貂免受致命挑战,而所有未接种疫苗的雪貂都会死于感染。它还降低了受感染雪貂上呼吸道和下呼吸道的病毒滴度。这些结果凸显了 mRNA 疫苗对高致病性禽流感甲型 H5N1 病毒的有效性,展示了其作为未来流感大流行疫苗平台的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An influenza mRNA vaccine protects ferrets from lethal infection with highly pathogenic avian influenza A(H5N1) virus
The global spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus poses a serious pandemic threat, necessitating the swift development of effective vaccines. The success of messenger RNA (mRNA) vaccine technology in the COVID-19 pandemic, marked by its rapid development and scalability, demonstrates its potential for addressing other infectious threats, such as HPAI A(H5N1). We therefore evaluated mRNA vaccine candidates targeting panzootic influenza A(H5) clade 2.3.4.4b viruses, which have been shown to infect a range of mammalian species, including most recently being detected in dairy cattle. Ferrets were immunized with mRNA vaccines encoding either hemagglutinin alone or hemagglutinin and neuraminidase, derived from a 2.3.4.4b prototype vaccine virus recommended by the World Health Organization. Kinetics of the immune responses, as well as protection against a lethal challenge dose of A(H5N1) virus, were assessed. Two doses of mRNA vaccination elicited robust neutralizing antibody titers against a 2022 avian isolate and a 2024 human isolate. Further, mRNA vaccination conferred protection from lethal challenge, whereas all unvaccinated ferrets succumbed to infection. It also reduced viral titers in the upper and lower respiratory tracts of infected ferrets. These results underscore the effectiveness of mRNA vaccines against HPAI A(H5N1), showcasing their potential as a vaccine platform for future influenza pandemics.
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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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