Development of a live oral attaching and effacing Escherichia coli vaccine candidate using Vibrio cholerae CVD 103-HgR as antigen vector

Microb Pathog. 2010 Jan;48(1):1-8. doi: 10.1016/j.micpath.2009.10.005. Epub 2009 Oct 28.


Attaching and effacing Escherichia coli (AEEC) share the ability to induce pedestal formation and intimate adherence of the bacteria to the intestinal epithelial cell and effacement of microvilli of epithelial tissue. The Locus of Enterocyte Effacement (LEE) pathogenicity island encodes the ability to induce attaching and effacing (A/E) lesions and contains the gene eae, which encodes intimin, an outer membrane protein that is an adhesin for A/E lesion formation. Here we show the utility of using intimin as a vaccine to protect rabbits from challenge with rabbit Enteropathogenic E. coli (REPEC), a member of the AEEC family. The C-terminal portion of intimin was delivered by the attenuated Vibrio cholerae vaccine strain CVD 103-HgR. To export intimin, a fusion was engineered with ClyA, a secreted protein from Salmonella enterica serovar Typhi. After immunization, antibodies specific to intimin from serum and bile samples were detected and moderate protection against challenge with a virulent REPEC strain was observed. Compared to animals immunized with vector alone, intimin-immunized rabbits exhibited reduced fecal bacterial shedding, milder diarrheal symptoms, lower weight loss, and reduced colonization of REPEC in the cecum. V. cholerae CVD 103-HgR shows promise as a vector to deliver antigens and confer protection against AEEC pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / immunology*
  • Animals
  • Antibodies, Bacterial / analysis
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bacterial Shedding / immunology
  • Bile / immunology
  • Cholera Vaccines / genetics*
  • Colony Count, Microbial
  • Disease Models, Animal
  • Escherichia coli Infections / prevention & control*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology*
  • Escherichia coli Vaccines / genetics
  • Escherichia coli Vaccines / immunology*
  • Feces / microbiology
  • Genetic Vectors*
  • Humans
  • Ileum / pathology
  • Male
  • Rabbits
  • Salmonella typhi / genetics
  • Serum / immunology
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology


  • Adhesins, Bacterial
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Cholera Vaccines
  • Escherichia coli Proteins
  • Escherichia coli Vaccines
  • Vaccines, Attenuated
  • cholera vaccine CVD 103-HgR
  • eaeA protein, E coli