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Clinical and Vaccine Immunology, February 2008, p. 359-366, Vol. 15, No. 2
1071-412X/08/$08.00+0     doi:10.1128/CVI.00399-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Protection against Shiga Toxin-Producing Escherichia coli Infection by Transcutaneous Immunization with Shiga Toxin Subunit B{triangledown}

C. Zhu,1,2 J. Yu,3 Z. Yang,1,3 K. Davis,1 H. Rios,1 B. Wang,2 G. Glenn,3 and E. C. Boedeker1,2*

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201,1 University of New Mexico School of Medicine, Albuquerque, New Mexico 87131,2 Iomai Corporation, Gaithersburg, Maryland 208783

Received 2 October 2007/ Accepted 1 November 2007

Enterohemorrhagic Escherichia coli (EHEC) strains are important human food-borne pathogens. EHEC strains elaborate potent Shiga toxins (Stx1, and/or Stx2) implicated in the development of hemorrhagic colitis (HC) or hemolytic-uremic syndrome (HUS). In this report, we evaluated the immunogenicity and protective efficacy of Stx1 subunit B (StxB1) administered by transcutaneous immunization (TCI). Three groups of Dutch Belted rabbits received patches containing StxB1, StxB1 in combination with Escherichia coli heat-labile enterotoxin (LT), or LT alone. An additional group of naïve rabbits served as controls. The protective efficacy following TCI with StxB1 was assessed by challenging rabbits with a virulent Stx1-producing strain, RDEC-H19A, capable of inducing HC and HUS in rabbits. Antibodies specific to StxB1 from serum and bile samples were determined by enzyme-linked immunosorbent assay and toxin neutralization test. Rabbits immunized with StxB1 demonstrated improved weight gain and reduced Stx-induced histopathology. Rabbits receiving StxB or StxB1/LT showed a significant increase in serum immunoglobulin G titers specific to StxB1 as well as toxin neutralization titers. These data demonstrated that the StxB delivered by TCI could induce significant systemic immune responses. Thus, Stx subunit B vaccine delivered by a patch for a high-risk population may be a practical approach to prevent (and/or reduce) Stx-induced pathology.

* Corresponding author. Mailing address: University of New Mexico School of Medicine, MSC10 5550, 1 University of New Mexico, Albuquerque, NM 87131. Phone: (505) 925-4153. Fax: (505) 925-4869. E-mail: eboedeker{at}salud.unm.edu

{triangledown} Published ahead of print on 14 November 2007.

Clinical and Vaccine Immunology, February 2008, p. 359-366, Vol. 15, No. 2
1071-412X/08/$08.00+0     doi:10.1128/CVI.00399-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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