Influenza poses a severe threat to global health. Despite the whole inactivated virus (WIV)‐based nasal vaccine being a promising strategy for influenza protection, the mucosal barrier is still a bottleneck of the nasal vaccine. Here, a catalytic mucosal adjuvant strategy for an influenza WIV nasal vaccine based on chitosan (CS) functionalized iron oxide nanozyme (IONzyme) is developed. The results reveal that CS‐IONzyme increases antigen adhesion to nasal mucosa by 30‐fold compared to H1N1 WIV alone. Next, CS‐IONzyme facilitates H1N1 WIV to enhance CCL20‐driven submucosal dendritic cell (DC) recruitment and transepithelial dendrite(TED) formation for viral uptake via the toll‐like receptor(TLR) 2/4‐dependent pathway. Moreover, IONzyme with enhanced peroxidase (POD)‐like activity by CS modification catalyzes a reactive oxygen species (ROS)‐dependent DC maturation, which further enhances the migration of H1N1 WIV‐loaded DCs into the draining lymph nodes for antigen presentation. Finally, CS‐IONzyme‐based nasal vaccine triggers an 8.9‐fold increase of IgA‐mucosal adaptive immunity in mice, which provides a 100% protection against influenza, while only a 30% protection by H1N1 WIV alone. This work provides an antiviral alternative for designing nasal vaccines based on IONzyme to combat influenza infection.

中文翻译：

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粘膜疫苗接种可通过催化免疫佐剂增强对流感的保护作用

流感对全球健康构成了严重威胁。尽管基于整个灭活病毒（WIV）的鼻疫苗是一种有希望的流感防护策略，但粘膜屏障仍是鼻疫苗的瓶颈。在这里，开发了基于壳聚糖（CS）功能化的氧化铁纳米酶（IONzyme）的流感WIV鼻疫苗的催化粘膜佐剂策略。结果表明，与单独的H1N1 WIV相比，CS-IONzyme将抗原与鼻粘膜的粘附力提高了30倍。接下来，CS-IONzyme促进H1N1 WIV增强CCL20驱动的黏膜下树突状细胞（DC）募集和经上皮样树突状（TED）形成，以通过Toll样受体（TLR）2/4依赖性途径吸收病毒。此外，通过CS修饰具有增强的过氧化物酶（POD）样活性的离子酶催化依赖活性氧（ROS）的DC成熟，这进一步增强了H1N1 WIV负载的DC向引流淋巴结转移以进行抗原呈递。最后，基于CS-IONzyme的鼻疫苗可触发小鼠IgA粘膜适应性免疫提高8.9倍，从而可提供100％的流感防护，而仅通过H1N1 WIV即可提供30％的防护。这项工作为设计基于IONzyme的鼻疫苗提供了抗病毒替代品，以抗击流感感染。它提供100％的流感防护，而仅H1N1 WIV仅提供30％的防护。这项工作为设计基于IONzyme的鼻疫苗提供了抗病毒替代品，以抗击流感感染。它提供100％的流感防护，而仅H1N1 WIV仅提供30％的防护。这项工作为设计基于IONzyme的鼻疫苗提供了一种抗病毒替代品，以抗击流感感染。