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

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)