Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus.
Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus.
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开发针对进化枝 2.3.4.4b H5 高致病性禽流感病毒的核苷修饰 mRNA 疫苗。
DOI：
10.1101/2023.04.30.538854
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Weissman,Drew
中科院分区：
文献类型：
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作者：
Furey,Colleen;Ye,Naiqing;Kercher,Lisa;DeBeauchamp,Jennifer;Crumpton,JeriCarol;Jeevan,Trushar;Patton,Christopher;Franks,John;Alameh,Mohamad-Gabriel;Fan,StevenHY;Phan,AnthonyT;Hunter,ChristopherA;Webby,RichardJ;Weissman,Drew
mRNA脂质纳米颗粒（LNP）疫苗在流感病毒大流行期间将是有用的，因为它们可以快速生产，并且不需要产生适应鸡蛋的疫苗种子库。来自H5进化支2.3.4.4b的高致病性禽流感病毒在野生和家禽中以前所未有的高水平传播，并有可能适应人类。在这里，我们从一个进化支2.3.4.4b H5分离物中生成了一种编码血凝素（HA）糖蛋白的mRNA脂质纳米颗粒（LNP）疫苗。H5 mRNA-LNP疫苗在雌性小鼠中引起强烈的T细胞和抗体反应，包括中和抗体和广泛反应性抗ha柄抗体。H5 mRNA-LNP疫苗在有或没有H1N1暴露史的雌性小鼠中产生的抗体水平与全灭活疫苗相似。最后，我们发现H5 mRNA-LNP疫苗在雄性雪貂中具有免疫原性，可以预防2.3.4.4b型H5N1病毒攻击后动物的发病和死亡。总之，我们的数据表明，在临床前动物模型中，表达2.3.4.4b H5的单价mRNA-LNP疫苗具有免疫原性和保护性。
mRNA lipid nanoparticle (LNP) vaccines would be useful during an influenza virus pandemic since they can be produced rapidly and do not require the generation of egg-adapted vaccine seed stocks. Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. Here, we generate an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. The H5 mRNA-LNP vaccine elicits strong T cell and antibody responses in female mice, including neutralizing antibodies and broadly-reactive anti-HA stalk antibodies. The H5 mRNA-LNP vaccine elicits antibodies at similar levels compared to whole inactivated vaccines in female mice with and without prior H1N1 exposures. Finally, we find that the H5 mRNA-LNP vaccine is immunogenic in male ferrets and prevents morbidity and mortality of animals following 2.3.4.4b H5N1 challenge. Together, our data demonstrate that a monovalent mRNA-LNP vaccine expressing 2.3.4.4b H5 is immunogenic and protective in pre-clinical animal models.