Hatta Masato, Hatta Yasuko, Choi Angela, Hossain Jaber, Feng Chenchen, Keller Matthew W, Ritter Jana M, Huang Ying, Fang Emma, Pusch Elizabeth A, Rowe Thomas, De La Cruz Juan A, Johnson Monique C, Liddell Jimma, Jiang Nannan, Stadlbauer Daniel, Liu Li, Bhattacharjee Arindam K, Rouse Joseph R, Currier Michael, Wang Li, Levine Min Z, Kirby Marie K, Steel John, Di Han, Barnes John R, Henry Carole, Davis C Todd, Nachbagauer Raffael, Wentworth David E, Zhou Bin
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
Moderna Inc., Cambridge, MA 02142, USA.
Sci Transl Med. 2024 Dec 18;16(778):eads1273. doi: 10.1126/scitranslmed.ads1273.
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.
高致病性禽流感（HPAI）A（H5N1）病毒的全球传播构成了严重的大流行威胁，因此需要迅速研发有效的疫苗。信使核糖核酸（mRNA）疫苗技术在新冠疫情中取得成功，其特点是研发迅速且具备可扩展性，这表明该技术在应对其他传染性威胁（如HPAI A（H5N1））方面具有潜力。因此，我们评估了针对大流行甲型（H5）2.3.4.4b分支病毒的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，最近在奶牛中也有发现。用编码单独血凝素或血凝素和神经氨酸酶的mRNA疫苗对雪貂进行免疫，这些疫苗来源于世界卫生组织推荐的一种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死剂量A（H5N1）病毒攻击的保护作用。两剂mRNA疫苗接种引发了针对2022年禽源毒株和2024年人源毒株的强大中和抗体滴度。此外，mRNA疫苗接种提供了对致死性攻击的保护，而所有未接种疫苗的雪貂均死于感染。它还降低了感染雪貂上、下呼吸道中的病毒滴度。这些结果强调了mRNA疫苗对HPAI A（H5N1）的有效性，展示了其作为未来流感大流行疫苗平台的潜力。
