Highly pathogenic avian influenza viruses (HPAIVs) pose a significant threat to human health, with high mortality rates, and require effective vaccines. We showed that, harnessed with novel RNA-mediated chaperone function, hemagglutinin (HA) of H5N1 HPAIV could be displayed as an immunologically relevant conformation on self-assembled chimeric nanoparticles (cNP). A tri-partite monomeric antigen was designed including: i) an RNA-interaction domain (RID) as a docking tag for RNA to enable chaperna function (chaperna: chaperone + RNA), ii) globular head domain (gd) of HA as a target antigen, and iii) ferritin as a scaffold for 24 mer-assembly. The immunization of mice with the nanoparticles (~46 nm) induced a 25–30 fold higher neutralizing capacity of the antibody and provided cross-protection from homologous and heterologous lethal challenges. This study suggests that cNP assembly is conducive to eliciting antibodies against the conserved region in HA, providing potent and broad protective efficacy.

高致病性禽流感病毒（HPAIV）对人类健康构成重大威胁，死亡率高，需要有效的疫苗。我们表明，利用新的 RNA 介导的伴侣功能，H5N1 HPAIV 的血凝素 (HA) 可以显示为自组装嵌合纳米粒子 (cNP) 上的免疫相关构象。设计了三部分单体抗原，包括：i) RNA 相互作用域 (RID) 作为 RNA 的对接标签，以实现伴侣功能（伴侣：伴侣 + RNA），ii) HA 的球状头部域 (gd) 作为靶抗原，以及 iii) 铁蛋白作为 24 聚体组装的支架。用纳米颗粒（~46 nm）对小鼠进行免疫诱导抗体的中和能力提高了 25-30 倍，并提供了对同源和异源致命挑战的交叉保护。