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Infection and Immunity, October 2005, p. 6523-6529, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6523-6529.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Recombinant Shiga Toxin B-Subunit-Keyhole Limpet Hemocyanin Conjugate Vaccine Protects Mice from Shigatoxemia

Paola Marcato,1 Thomas P. Griener,2 George L. Mulvey,2 and Glen D. Armstrong2*

Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2H7, Canada,1 Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Center, Calgary, AB T2N 4N1, Canada2

Received 8 April 2005/ Returned for modification 12 May 2005/ Accepted 2 June 2005

Enterohemorrhagic Escherichia coli (EHEC) causes hemorrhagic colitis in humans and, in a subgroup of infected subjects, a more serious condition called hemolytic-uremic syndrome (HUS). These conditions arise because EHEC produces two antigenically distinct forms of Shiga toxin (Stx), called Stx1 and Stx2. Despite this, the production of Stx2 by virtually all EHEC serotypes and the documented role this toxin plays in HUS make it an attractive vaccine candidate. Previously, we assessed the potential of a purified recombinant Stx2 B-subunit preparation to prevent Shigatoxemia in rabbits. This study revealed that effective immunization could be achieved only if endotoxin was included with the vaccine antigen. Since the presence of endotoxin would be unacceptable in a human vaccine, the object of the studies described herein was to investigate ways to safely augment, in mice, the immunogenicity of the recombinant Stx2 B subunit containing <1 endotoxin unit per ml. The study revealed that sera from mice immunized with such a preparation, conjugated to keyhole limpet hemocyanin and administered with the Ribi adjuvant system, displayed the highest Shiga toxin 2 B-subunit-specific immunoglobulin G1 (IgG1) and IgG2a enzyme-linked immunosorbent assay titers and cytotoxicity-neutralizing activities in Ramos B cells. As well, 100% of the mice vaccinated with this preparation were subsequently protected from a lethal dose of Stx2 holotoxin. These results support further evaluation of a Stx2 B-subunit-based human EHEC vaccine.

* Corresponding author. Mailing address: Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, AB T2N 4N1, Canada. Phone: (403) 220-6885. Fax: (403) 270-2772. E-mail: glen.armstrong{at}ucalgary.ca.

Editor: J. T. Barbieri

Infection and Immunity, October 2005, p. 6523-6529, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6523-6529.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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