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.

中文翻译：

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流感 mRNA 疫苗可保护雪貂免受高致病性甲型禽流感 （H5N1） 病毒的致命感染


高致病性甲型禽流感 （HPAI） 甲型 （H5N1） 病毒的全球传播构成了严重的大流行威胁，需要迅速开发有效的疫苗。信使 RNA （mRNA） 疫苗技术在 COVID-19 大流行中的成功以其快速发展和可扩展性为标志，表明其在应对其他感染威胁方面的潜力，例如 HPAI A （H5N1）。因此，我们评估了针对泛动物流感 A （H5） 分支 2.3.4.4b 病毒的 mRNA 候选疫苗，该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。雪貂使用单独编码血凝素或血凝素和神经氨酸酶的 mRNA 疫苗进行免疫，这些疫苗源自世界卫生组织推荐的 2.3.4.4b 原型疫苗病毒。评估了免疫反应的动力学，以及对致命攻击剂量的甲型 （H5N1） 病毒的保护作用。两剂 mRNA 疫苗接种引发了针对 2022 年禽分离株和 2024 年人类分离株的强大中和抗体滴度。此外，mRNA 疫苗接种可以保护它们免受致命攻击，而所有未接种疫苗的雪貂都死于感染。它还降低了受感染雪貂上呼吸道和下呼吸道的病毒滴度。这些结果强调了 mRNA 疫苗对甲型 HPAI （H5N1） 的有效性，展示了它们作为未来流感大流行疫苗平台的潜力。