Abstract |
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.
|
Authors | Monika Bokori-Brown, Charlotte A Hall, Charlotte Vance, Sérgio P Fernandes da Costa, Christos G Savva, Claire E Naylor, Ambrose R Cole, Ajit K Basak, David S Moss, Richard W Titball |
Journal | Vaccine
(Vaccine)
Vol. 32
Issue 23
Pg. 2682-7
(May 13 2014)
ISSN: 1873-2518 [Electronic] Netherlands |
PMID | 24709588
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved. |
Chemical References |
- Bacterial Toxins
- Bacterial Vaccines
- Clostridium perfringens epsilon-toxin
- Recombinant Proteins
- Vaccines, Synthetic
|
Topics |
- Animals
- Bacterial Toxins
(immunology)
- Bacterial Vaccines
(immunology)
- Dogs
- Enterotoxemia
(prevention & control)
- Female
- Madin Darby Canine Kidney Cells
- Mice
- Mice, Inbred BALB C
- Mutagenesis, Site-Directed
- Neutralization Tests
- Protein Structure, Tertiary
- Rabbits
- Recombinant Proteins
(immunology)
- Vaccines, Synthetic
(immunology)
|