黏膜递送广谱流感疫苗的前沿进展

Frontier Advances in Mucosal Delivery of Broadly Protective Influenza Vaccines

摘要

流感病毒持续发生抗原变异，严重威胁公共卫生安全。当前季节性流感疫苗根据世界卫生组织对病毒流行株的预测进行年度更新，然而仍存在预测精度有限、保护范围窄、黏膜应答弱以及对不同亚型和变异病毒株交叉保护能力有限等问题。开发经黏膜递送的广谱流感疫苗，为增强呼吸道局部免疫、拓宽疫苗保护范围、降低病毒感染风险提供了新方向。综述系统梳理了广谱流感疫苗研发策略及临床研究进展，重点介绍经黏膜递送的广谱流感疫苗在抗原设计、疫苗平台及递送系统方面的最新研究，总结通过免疫策略优化增强疫苗效力、拓展疫苗保护范围的新思路，并分析疫苗临床转化面临的挑战与发展前景，以期为相关疫苗的设计、研发和转化应用提供参考。

Abstract

Influenza viruses undergo continuous antigenic variation, posing a serious threat to public health. Current seasonal influenza vaccines are updated annually based on World Health Organization predictions of circulating strains. However, they still face several limitations, including limited prediction accuracy, narrow breadth of protection, weak mucosal immune responses, and insufficient cross-protection against different viral subtypes and variant strains. The development of broadly protective influenza vaccines delivered via mucosal routes provides a promising strategy to enhance local immunity in the respiratory tract, broaden vaccine protection, and reduce the risk of viral infection. This review systematically summarizes current strategies for the development of broadly protective influenza vaccines and advances in their clinical research, with a particular focus on recent progress in antigen design, vaccine platforms, and delivery systems for mucosally delivered broadly protective influenza vaccines. We further summarize emerging immunization strategies for enhancing vaccine efficacy and broadening the breadth of protection, and analyze the challenges and future perspectives associated with clinical translation. This review aims to provide insights for the design, development, and translational application of these vaccines.

关键词

流感疫苗 / 广谱疫苗 / 黏膜递送 / 交叉保护 / 免疫策略

Key words

influenza vaccines / broadly protective vaccines / mucosal delivery / cross protection / immunization strategy

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基金资助

国家自然科学基金青年科学基金资助项目（C 类）(No. 82502216)