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Virus-like particle vaccine: mechanisms, applications and challenges
JIN Xueyao, ZHANG Peng
2026, 43 (3):
12.
doi: 10.3969/j.issn.2095-1736.2026.03.012
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.
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