数字农科院2.0

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： 贾琦;;相浩雨;;乐婷;;王晶;;常继涛;;王芳;;孙超;;太万博;;姜志刚;;尹鑫

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

期刊名称： Frontiers in Immunology

ISSN： 1664-3224

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Clostridium perfringens (C. perfringens), a ubiquitous Gram-positive bacterium Q8 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. Here, we engineered a lipid nanoparticle encapsulated CPACTD 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. The 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. 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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