Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia

被引：45

作者：

Bokori-Brown, Monika ^{[1
]}

Hall, Charlotte A. ^{[1
]}

Vance, Charlotte ^{[1
]}

da Costa, Sergio P. Fernandes ^{[1
]}

Savva, Christos G. ^{[2
]}

Naylor, Claire E. ^{[2
]}

Cole, Ambrose R. ^{[2
]}

Basak, Ajit K. ^{[2
]}

Moss, David S. ^{[2
]}

Titball, Richard W. ^{[1
]}

机构：

[1] Univ Exeter, Coll Life & Environm Sci, Exeter EX4 4QD, Devon, England

[2] Univ London Birkbeck Coll, Dept Biol Sci, London WC1E 7HX, England

来源：

VACCINE | 2014年 / 32卷 / 23期

基金：

英国惠康基金;

关键词：

Clostridium perfringens; Epsilon toxin pore-forming toxin; Enterotoxemia; Recombinant vaccine; LAMBDA-TOXIN; BINDING; SHEEP; ACTIVATION; CELLS; SITE;

D O I：

10.1016/j.vaccine.2014.03.079

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Epsilon toxin (Etx) is a beta-pore-forming toxin produced by Clostridium perfringens toxinotypes B and D and plays a key role in the pathogenesis of enterotoxemia, a severe, often fatal disease of ruminants that causes significant economic losses to the farming industry worldwide. This study aimed to determine the potential of a site-directed mutant of Etx (Y30A-Y196A) to be exploited as a recombinant vaccine against enterotoxemia. Replacement of Y30 and Y196 with alanine generated a stable variant of Etx with significantly reduced cell binding and cytotoxic activities in MDCK.2 cells relative to wild type toxin (>430-fold increase in CT50) and Y30A-Y196A was inactive in mice after intraperitoneal administration of trypsin activated toxin at 1000x the expected LD50 dose of trypsin activated wild type toxin. Moreover, polyclonal antibody raised in rabbits against Y30A-Y196A provided protection against wild type toxin in an in vitro neutralisation assay. These data suggest that Y30A-Y196A mutant could form the basis of an improved recombinant vaccine against enterotoxemia. (C) 2014 The Authors. Published by Elsevier Ltd.

引用

页码：2682 / 2687

页数：6

共 23 条

[1] STRUCTURAL STUDIES ON EPSILON-PROTOTOXIN OF CLOSTRIDIUM-PERFRINGENS TYPE-D - LOCALIZATION OF SITE OF TRYPTIC SCISSION NECESSARY FOR ACTIVATION TO EPSILON-TOXIN [J].