A glycoprotein D-targeted lipid nanoparticle-encapsulated mRNA vaccine elicits strong protective immunity against pseudorabies virus
文献类型： 外文期刊
作者： Yue Sun;;Shi-Jia Xu;;Yongfei Zhou;;Yanhe Zhang;;Hongliang Zhang;;Ting Le;;Yuan-Zhe Bai;; Cui-Hong Rao;; Shanshan Huo;; Tianceng Zhou;; Tong-Qing An;; Xin Yin;; Fei Yu;;Xue-Hui Cai; Yan-Dong Tang
关键词： mRNA
期刊名称： Journal of Virology
ISSN： 0022-538X
年卷期： 2025 年
页码：
收录情况： SCIE（2025版）
摘要： The pseudorabies virus (PRV), a highly contagious pathogen with zoonotic potential, continues to threaten swine production and public health due to the emergence of virulent variants and insufficient protection conferred by conventional live attenuated vaccines. Although commercial vaccines are safe for pigs, their residual pathogenicity in other susceptible species underscores the demand for universally safe alternatives. Here, we engineered a lipid nanoparticle-encapsulated mRNA vaccine (mRNA-LNPs) expressing PRV glycoprotein D (gD) and evaluated its efficacy in murine and porcine models. In mice, vaccination with gD mRNA-LNPs elicited potent neutralizing antibodies and provided complete protection against lethal PRV challenge. In piglets, immunization induced rapid humoral immune responses, significantly reduced viral loads in tissues and viral shedding post-challenge, and alleviated histopathological damage. Mechanistically, except for its ability to elicit neutralizing antibodies, the vaccine also stimulated antigen-specific CD3+CD4+ T-cell and CD3+CD8+ T-cell proliferation and enhanced IFN-γ production, demonstrating robust activation of both humoral and cellular immunity. These findings establish gD mRNA-LNPs as a safe, effective, and broadly applicable vaccine candidate for PRV control across susceptible species, with advantages in scalability and biosafety over traditional platforms.
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