TY - JOUR
T1 - Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia
AU - Bokori-Brown, Monika
AU - Hall, Charlotte
AU - Vance, Charlotte
AU - Fernandes da Costa, SP
AU - Savva, CG
AU - Naylor, Claire
AU - Cole, AR
AU - Basak, AK
AU - Moss, DS
AU - Titball, Richard
N1 - This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence
( https://creativecommons.org/licenses/by/3.0/ )which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright © 2014 The Authors. Published by Elsevier Ltd.
PY - 2014/5/13
Y1 - 2014/5/13
N2 - Epsilon toxin (Etx) is a β-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 1000× 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.
AB - Epsilon toxin (Etx) is a β-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 1000× 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.
U2 - 10.1016/j.vaccine.2014.03.079
DO - 10.1016/j.vaccine.2014.03.079
M3 - Article
SN - 0264-410X
VL - 32
SP - 2682
EP - 2687
JO - Vaccine
JF - Vaccine
IS - 23
ER -