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