Safety and immunogenicity of escalating dosages of a single oral administration of peru-15 pCTB, a candidate live, attenuated vaccine against enterotoxigenic Escherichia coli and Vibrio cholerae

Academic Article


  • © 2015, American Society for Microbiology. All Rights Reserved. Enterotoxigenic Escherichia coli (ETEC) organisms are a leading cause of infectious diarrhea in developing countries. A live, attenuated cholera strain that expresses high levels of the nontoxic B subunit of cholera toxin, which might also serve as an ETEC protective antigen, was evaluated for safety, excretion, and immunogenicity in healthy volunteers. We enrolled four inpatient dose-escalation cohorts of 15 to 16 eligible subjects to randomly (3: 1) receive a single oral dose of vaccine or placebo (buffer alone), evaluating 1×107, 1×108, 1×109, and 1×1010 CFU of the vaccine. The vaccine was well tolerated, although some subjects experienced moderate diarrhea. The serum Inaba vibriocidal antibody response appeared to display a dose-response relationship with increasing dosages of vaccine, plateauing at the 109-CFU dosage. The serum antitoxin (cholera toxin and heat-labile enterotoxin) antibody seroconversion rate (4-fold increase over baseline) also appeared to display a dose-response relationship. The vaccine strain was excreted in stool cultures, displaying a dose-response relationship. A single oral dose of Peru-15 pCTB at dosages up to 1×1010 CFU was safe and immunogenic in this first-in-human trial. These encouraging data support the ongoing clinical development of this candidate combined cholera and ETEC vaccine. (This study has been registered at under registration no. NCT00654108.).
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    Author List

  • Chen WH; Garza J; Choquette M; Hawkins J; Hoeper A; Bernstein DI; Cohenb MB
  • Start Page

  • 129
  • End Page

  • 135
  • Volume

  • 22
  • Issue

  • 1