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A lipid nanoparticle encapsulated CPA-CTD mRNA vaccine provides protection against Clostridium perfringens-driven diseases

文献类型: 外文期刊

作者: Qi Jia;Haoyu Xiang;Ting Le;Jing Wang;Jitao Chang;Fang Wang;Chao Sun;Wanbo Tai;Zhigang Jiang;Xin Yin

作者机构:

关键词: Clostridium perfringens alpha-toxin;enterotoxemia;gas gangrene;mRNA vaccine;protective efficacy

期刊名称: Frontiers in Immunology

ISSN:

年卷期: 2026 年 16 卷

页码:

收录情况: SCIE(2025版)

摘要: Introduction: Clostridium perfringens (C. perfringens), a ubiquitous Gram-positive bacterium in the environment and mammalian gut flora, is a leading cause of enterotoxemia in animals, necrotizing enteritis in humans and animals, and gas gangrene in both, attributed to its diverse exotoxin profile. Alpha-toxin, a pivotal virulence factor produced by all C. perfringens serotypes, plays a central role in the pathogenicity of these diseases. Methods: Here, we engineered a lipid nanoparticle encapsulated CPA-CTD mRNA vaccine targeting the conserved C-terminal domain of C. perfringens alpha-toxin and rigorously assessed its immunogenicity and protective efficacy in mouse and bovine models. Results: The CPA-CTD mRNA vaccine induced strong humoral and cellular immune responses in mice, particularly in promoting the rapid production of specific IgG and mucosal IgA antibodies, as well as enhancing T cell immune responses, surpassing conventional subunit vaccines. Protection was confirmed in dual challenge models --enterotoxemia and gas gangrene --where the vaccine provided complete immunity against lethal doses of alpha-toxin and C. perfringens infection. In cattle, the CPA-CTD mRNA vaccine induced high-titer IgG antibodies and toxin-neutralizing antibodies. Notably, immunization of pregnant cows led to efficient transfer of these antibodies via colostrum to newborn calves, providing passive protection. Discussion: These results demonstrate that the CPA-CTD mRNA vaccine provides rapid and robust immune protection against C. perfringens alpha-toxin-associated diseases, with promising potential for applications in both veterinary and human health.

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