Protection against Shiga toxin-producing Escherichia coli infection by transcutaneous immunization with Shiga toxin B subunit

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201; University of New Mexico School of Medicine, Albuquerque, NM 87131; Iomai Corporation, Gaithersburg, MD 20878

^* To whom correspondence should be addressed. Email: eboedeker{at}salud.unm.edu.

	Abstract

Enterohemorrhagic E. coli (EHEC) are important human food-borne pathogens. EHEC elaborate potent Shiga toxins (Stx, 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 the Stx1 B subunit (Stx1B) administered by transcutaneous immunization (TCI). Three groups of Dutch Belted rabbits received patches containing Stx1B, or Stx1B in combination with E. coli heat-labile enterotoxin (LT), or LT alone. An additional group of naïve rabbits served as controls. The protective efficacy following TCI with Stx1B was assessed by challenging rabbits with a virulent Stx-1-producing strain, RDEC-H19A, capable of inducing HC and HUS in rabbits. Antibodies specific to Stx1B from serum and bile samples were determined by ELISA and toxin neutralization test. Rabbits immunized with Stx1B demonstrated improved weight gain and reduced Stx-induced-histopathology. Rabbits receiving Stx1B or Stx1B/LT showed a significant increase in serum IgG titers specific to Stx1B as well as toxin neutralization titers. These data demonstrated that the StxB delivered by TCI could induce significant systemic immune responses. Thus, Stx B subunit vaccines delivered by a patch for a high-risk population may be a practical approach to prevent (and/or reduce) Stx-induced histopathology.