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

Clin Vaccine Immunol. 2015 Jan;22(1):129-35. doi: 10.1128/CVI.00560-14. Epub 2014 Nov 19.

Abstract

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 ×10(7), 1 ×10(8), 1 ×10(9), and 1 ×10(10) 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 10(9)-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 ×10(10) 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 ClinicalTrials.gov under registration no. NCT00654108.).

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood
  • Antitoxins / blood
  • Cholera Vaccines / administration & dosage
  • Cholera Vaccines / adverse effects*
  • Cholera Vaccines / immunology*
  • Diarrhea / pathology
  • Dose-Response Relationship, Immunologic
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Enterotoxigenic Escherichia coli / immunology*
  • Escherichia coli Vaccines / administration & dosage
  • Escherichia coli Vaccines / adverse effects*
  • Escherichia coli Vaccines / immunology*
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Treatment Outcome
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Vibrio cholerae / immunology*
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Antitoxins
  • Cholera Vaccines
  • Escherichia coli Vaccines
  • Peru 15
  • Placebos
  • Vaccines, Attenuated

Associated data

  • ClinicalTrials.gov/NCT00654108