生物学杂志

生物学杂志 ›› 2026, Vol. 43 ›› Issue (3): 12-.doi: 10.3969/j.issn.2095-1736.2026.03.012

• 大健康专题 • 上一篇    下一篇

病毒样颗粒疫苗研究进展：技术原理、应用与挑战

金雪尧1， 张　鹏1,2   

  1. 1. 合肥综合性国家科学中心大健康研究院， 合肥 230601；
    2. 免疫应答与免疫治疗全国重点实验室， 合肥 230027
  • 出版日期:2026-06-18 发布日期:2026-06-16
  • 通讯作者: 张鹏，高级研究员，研究方向为HIV-1和病毒疫苗开发和应用，E-mail：zhangp@ihm.ac.cn
  • 作者简介:金雪尧，博士，研究方向为结构生物学，E-mail：jinxy@ihm.ac.cn
  • 基金资助:
    合肥综合性国家科学中心大健康研究院项目（2023KYQD010）

#br# Virus-like particle vaccine: mechanisms, applications and challenges

JIN Xueyao1, ZHANG Peng1,2   

  1. 1. Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei 230601, China;
    2. State Key Laboratory of Immune Response and Immunotherapy, Hefei 230027, China
  • Online:2026-06-18 Published:2026-06-16

摘要： 本综述系统梳理病毒样颗粒（VLP）疫苗的研究进展，首先比较主流的生产技术路线，包括利用酵母、昆虫细胞、植物细胞等体外表达系统制备重组VLPs（例如：乙肝病毒疫苗Recombivax HB及人乳头瘤病毒9价疫苗Gardasil-9），以及通过 mRNA 技术在体内表达包膜病毒样颗粒（eVLPs）的创新方式；其次依据模拟病毒相似度将VLPs分为微观尺度接近型、中度模拟型和高度模拟型等3类；解析其免疫激活机制，包括抗原提呈细胞（APCs）的摄取与激活、T 细胞免疫激活路径及B细胞激活的两种机制（T 细胞依赖性与非依赖性），并强调VLP结构（20~200 nm粒径、重复抗原表位）对免疫增强的关键作用。此外，本综述还探讨免疫佐剂与VLP的协同作用，对比VLP疫苗与传统蛋白疫苗、DNA/mRNA疫苗、病毒载体疫苗和灭活/减毒疫苗的差异，指出当前VLP疫苗面临的抗原构象不稳定、广谱表位预测难、稀有B细胞激活难等技术瓶颈，以及靶向递送、缓释技术、抗体类型调控等创新方向。最后，展望VLP疫苗在神经退行性疾病治疗、癌症免疫治疗、阿片类药物成瘾干预等领域的应用潜力，如果进一步解决稳定性、成本等问题，结合跨学科技术融合，将成为应对全球健康挑战的重要疫苗平台。

关键词: 病毒样颗粒, 疫苗, 衣壳蛋白, 自组装, 抗原设计

Abstract: This review summarizes the research progress of virus-like particle （VLP） vaccines. First, it recaps the production technology routes, including the preparation of recombinant VLPs usingin vitroexpression systems such as yeast, insect cells, and plant cells （e.g., the hepatitis B vaccine Recombivax HB and the HPV vaccine Gardasil-9）, as well as innovative methods for expressing enveloped virus-like particles （eVLPs）in vivovia mRNA technology. Second, VLPs can be classified into three categories based on their structural similarity to the viruses they mimic: size-similar VLPs, intermediate-mimic VLPs, and well-mimic VLPs. The immune activation mechanisms of VLPs, including the uptake and activation of antigen-presenting cells （APCs）, the T-cell immune activation pathway, and the two mechanisms of B-cell activation （T-cell-dependent and T-cell-independent）, are overviewed. It also highlights the critical role of VLP structural features, such as particle size （20－200 nm） and repetitive antigen epitopes-in enhancing immune responses. In addition, this review discusses the synergistic effect between immune adjuvants and VLPs and compares VLP vaccines and other vaccine types, including conventional protein subunit vaccines, DNA/mRNA vaccines, viral vector vaccines, and inactivated/live attenuated vaccines. It delineates current technical bottlenecks of VLP vaccines, such as unstable antigen conformation, difficulties in predicting broad-spectrum epitopes, and limited activation of rare B cell populations, as well as innovative directions including targeted delivery systems, sustained-release technologies, and modulation of antibody isotype responses. Finally, it prospects the potential applications of VLP vaccines in the treatment of neurodegenerative diseases, cancer immunotherapy, and opioid addiction intervention. It is believed that by addressing existing limitations such as stability and production costs, and through integration with interdisciplinary technologies, VLP-based vaccines are poised to become an important vaccine platform for addressing global health challenges.

Key words: virus-like particle （VLP）, vaccine, capsid protein, self-assembly, antigen design

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