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.

引用

页数：7

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