Efficacy Study of IM Administered CssBA+dmLT Against Moderate-severe Diarrhea in Human Infection Model With ETEC Strain B7A in Healthy Adults

The study is designed to evaluate the safety, immunogenicity, and efficacy of the intramuscular administration of a CS6 based vaccine (CssBA) against ETEC co-administered with double mutant labile toxin (dmLT) in preventing moderate-severe diarrhea (MSD) following challenge with ETEC strain B7A in healthy adults. Approximately 72 adult participants, divided into 4 cohorts of 18, will be randomized 1:1 to receive vaccine (45 micrograms CssBA with 0.5 micrograms dmLT) or placebo (normal saline) on an outpatient basis. All participants will receive 3 intramuscular (IM) doses of vaccine or placebo at 3-week intervals (days 1, 22 and 43). Following vaccination, participants will be followed as outpatients for safety using a memory aid from the time of each vaccination through 7 days post each vaccination. Approximately 28 days (plus or minus 1 day) after receipt of the 3rd dose of study agent, participants meeting challenge criteria will be admitted to an inpatient unit and be administered an oral dose of 1 x 10\^10 cfu (colony-forming unit) of ETEC strain B7A. After receipt of challenge agent, the participant will fast for 90 minutes. Participants will be monitored daily for diarrhea and other signs/symptoms of enteric illness. All stool will be collected and graded, and loose stools (grade 3-5) will be weighed. Five days after challenge (or earlier if clinically indicated), participants will be treated with ciprofloxacin, except in cases of known allergy or intolerance in which case trimethoprim-sulfamethoxazole will be used. Participants will be discharged from the inpatient unit when they have completed their 3-day antibiotic course and are able to care for themselves, including maintaining hydration status. Follow-up outpatient visits for 5 days and 4 weeks after discharge will monitor safety and immunologic parameters, and a phone visit will be conducted 6 months after last dose of study agent. The primary objectives are: 1) Estimate CssBA+dmLT efficacy in preventing moderate-severe diarrhea (MSD) following challenge with ETEC strain B7A in healthy adults. 2) Evaluate the safety of intramuscular injection of CssBA+dmLT. The secondary objectives are: 1)Determine illness severity following ETEC B7A challenge in participants who received CssBA+dmLT vs placebo using an evidence-based disease severity score (1). 2)Evaluate ETEC CS6- and LT-specific serum IgG and IgA responses following vaccination and challenge. 3)Evaluate ETEC CS6- and LT-specific IgG and IgA in Antibodies from Lymphocyte Supernatant (ALS) following vaccination and 4) Determine the prevalence and duration of fecal shedding of B7A following challenge.