Mechanistic investigation of calcium phosphate mineralization potentiating the cellular immune response of foot-and-mouth disease virus-like particle vaccines

文献类型： 外文期刊

第一作者： Teng, Zhidong

作者： Teng, Zhidong;Li, Jiajun;Ren, Mei;Xie, Qianqian;Dong, Hu;Zhou, Jingjing;Mu, Suyu;Bai, Manyuan;Sun, Shiqi;Guo, Huichen;Guo, Huichen;Guo, Huichen

作者机构：

期刊名称：NANOSCALE （ 影响因子：5.1； 五年影响因子：5.6 ）

ISSN： 2040-3364

年卷期： 2025 年 17 卷 25 期

页码：

收录情况： SCI

摘要： Virus-like particles (VLPs), composed of structural proteins, have emerged as a promising vaccine platform for preventing infectious diseases due to their outstanding advantages. Enhancing immune responses specific to VLPs, particularly cellular immunity, has emerged as a pivotal area of current immunological research. The nanovaccines for the foot-and-mouth disease virus (FMDV) composed of VLPs mineralized with calcium phosphate (VLPs-CaP), developed based on biomineralization principles, demonstrates superior immunogenicity. In this study, we elucidated the efficacy and mechanism of VLPs-CaP in eliciting cellular immune responses. The results demonstrated that VLPs-CaP were efficiently internalized by dendritic cells (DCs) via energy-dependent endocytosis mediated by actin, microtubules, and clathrin. Upon uptake, VLPs-CaP decomposed within lysosomes, leading to the release of Ca2+ ions and an increase in lysosomal permeability. This facilitates the escape of VLPs into the cytoplasm for cross-presentation. Furthermore, CaP mineralization enhanced the level of activation of DCs by FMDV VLPs, evidenced by elevated expression of CD40 and CD86, and the secretion of IL-2 and IL-12p70. Immunization studies in mice revealed that VLPs-CaP elicited higher levels of specific antibodies compared to unmineralized VLPs; notably, there was an increased IgG2a/IgG1 ratio along with a greater number of cytotoxic T lymphocytes (CTLs). This study elucidated the mechanism by which CaP-mineralized VLPs induce cellular immune responses, offering new insights and strategies aimed at enhancing the cellular immune efficacy of VLP-based vaccines that primarily elicit humoral immunity.

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