生物学杂志

生物学杂志 ›› 2026, Vol. 43 ›› Issue (3): 1-.doi: 10.3969/j.issn.2095-1736.2026.03.001

• 大健康专题 •    下一篇

泛冠状病毒疫苗的研发策略与技术进展

杨芸茹1， 陈业恬2， 金腾川1,2,3   

  1. 1. 中国科学技术大学 生命科学与医学部， 合肥 230027； 2. 中国科学技术大学 先进技术研究院，
    合肥 230088； 3. 合肥综合性国家科学中心大健康研究院， 合肥 230601
  • 出版日期:2026-06-18 发布日期:2026-06-16
  • 通讯作者: 金腾川，教授，研究方向为感染与免疫的结构生物学，E-mail：jint@ustc.edu.cn
  • 作者简介:杨芸茹，博士，研究方向为冠状病毒疫苗抗原设计及开发，E-mail：yyr1107@mail.ustc.edu.cn
  • 基金资助:
    中国国家重点研发计划（2022YFC2304102， 2022YFC2303300）； 中国科学院战略性先导科技专项（XDB0490000， XDB0940301）； 国家自然科学基金项目（82272301）； 中国科学技术大学“双一流”建设专项科研经费（YD9100002056）

Strategic and technical advancements in pan-coronavirus vaccine development

YANG Yunru1, CHEN Yetian2, JIN Tengchuan1,2,3   

  1. 1. Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China;
    2. Institute of Advanced Technology, University of Science and Technology of China, Hefei 230088, China;
    3. Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China
  • Online:2026-06-18 Published:2026-06-16

摘要： 第一代新型冠状病毒疫苗在应对病原体持续变异及阻断病毒传播方面存在显著局限。为开发具备跨变异株保护能力的泛冠状病毒疫苗，本文对从抗原设计到递送系统优化的研发策略进行了系统论述。文章重点分析了基于S2亚基构象重塑与多表位重组的抗原工程，探讨了利用蛋白质纳米颗粒多价展示、mRNA原位表达与病毒载体高效转导调控免疫应答的机制。针对呼吸道局部防御，本文阐述了克服黏膜耐受、诱导分泌型IgA与组织驻留记忆细胞的黏膜免疫策略，并进一步强调了确立免疫替代终点等标准化临床评价体系的必要性。综上所述，整合结构免疫学、先进递送平台与监管科学，构建主动防御型的泛冠状病毒疫苗体系，是应对未来新型变异株及跨物种传播威胁的核心方向。

关键词: 泛冠状病毒疫苗, 抗原工程, 递送系统, 黏膜免疫, 免疫替代终点

Abstract: First-generation COVID-19 vaccines exhibited significant limitations in countering continuous pathogen evolution and intercepting viral transmission. To develop pan-coronavirus vaccines with cross-variant protective efficacy, this review provided a systematic discussion of research and development strategies, ranging from antigen design to delivery system optimization. The analysis focused on antigen engineering based on S2 subunit conformational remodeling and multi-epitope recombination, while exploring the mechanisms of immune response modulation via multivalent display on protein nanoparticles, viain situexpression using mRNA platforms, and via efficient transduction with viral vectors. Regarding localized respiratory defense, the review elaborated on mucosal immunity strategies to overcome mucosal tolerance and induce secretory IgA and tissue-resident memory cells, further emphasizing the necessity of establishing standardized clinical evaluation systems such as the identification of correlates of protection. In conclusion, integrating structural immunology, advanced delivery platforms, and regulatory science to construct a proactive pan-coronavirus vaccine framework is the pivotal direction for addressing future threats from novel variants and cross-species transmission.

Key words: pan-coronavirus vaccines, antigen engineering, delivery systems, mucosal immunity, correlates of protection

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