A non-toxic recombinant Clostridium septicum a toxin induces protective immunity in mice and rabbits

被引：0
|
作者：
Du, Jige [1 ]
Meki, Irene [2 ]
Li, Qianlin [1 ]
Liu, Ying [1 ]
Zhu, Zhen [1 ]
Pan, Chenfan [1 ]
Xia, Yingju [1 ]
Fu, Lizhi [3 ]
Yang, Liu [3 ]
Zhang, Suhui [3 ]
Yin, Chunsheng [1 ]
Luo, Yufeng [1 ]
Wang, Tuanjie [1 ]
Liu, Bo [1 ,2 ]
Chen, Xiaoyun [1 ]
机构：
[1] China Inst Vet Drug Control, Beijing, Peoples R China
[2] IAEA, Vienna, Austria
[3] Chongqing Acad Anim Sci, Chongqing 402460, Peoples R China
来源：
TOXICON | 2023年 / 233卷
关键词：
Clostridium septicum alpha toxin; Recombinant expression; Non-toxic; Antigenicity Braxy; PERFRINGENS EPSILON-TOXIN; ALPHA-TOXIN; MUTANT; IDENTIFICATION; SIMILARITY; TURKEYS; VACCINE; DOMAIN; BETA;
D O I：
10.1016/j.toxicon.2023.107234
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Clostridium septicum alpha toxin (CSA) plays significant roles in ruminant's braxy. Genetically engineered CSA has been shown to function as a potential vaccine candidate in the prevention of the disease caused by Clostridium septicum. In the present study, we synthesized a non-toxic recombinant, rCSA(m4/TMD) by introducing four amino acid substitutions (C86L/N296A/H301A/W342A) and 11-amino-acid deletion (residues 212 to 222). Compared to recombinant CSA, rCSA(m4/TMD) showed no cytotoxicity to MDCK cells and was not fatal to mice. Moreover, rCSA(m4/TMD) could protect immunized mice against 5 x mouse LD100 (100% lethal dose) of crude CSA without obvious pathological change. Most importantly, rabbits immunized with rCSA(m4/TMD) produced high titers of neutralizing antibodies which protected the rabbits against crude CSA challenge. These data suggest that genetically detoxified rCSA(m4/TMD) is a potential subunit vaccine candidate against braxy.
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页数：7
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