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.

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 ClinicalTrials. gov under registration no. NCT00654108.) Downloaded from http:// cvi. asm. org/ on February 4, 2015 by Institute Thomson Reuters