The purpose of this study is to determine whether a live, oral, combined Shigella-ETEC vaccine candidate, known as strain CVD 1208S-122, is safe and immunogenic.
The purpose of this study is to determine whether a live, oral, combined Shigella-ETEC vaccine candidate, known as strain CVD 1208S-122, is safe and immunogenic. This will be a phase 1, double-blind, placebo-controlled, dose-escalating, single-center study, involving three vaccine dosage escalation cohorts (10\^8, 10\^9, and 10\^10 cfu vaccine organisms). Each of the three dose-escalation cohorts will consist of 8 study participants who will be randomly allocated to receive either vaccine (n=6) or placebo (n=2), as a single, oral dose. An independent Safety Monitoring Committee (SMC) will review the available safety data for Cohorts 1 - 3 through 7 days post-vaccination before proceeding to the enrollment of the next cohort. The fourth cohort will be an adaptive design cohort consisting of 30 study participants to be randomly allocated to receive either two doses of vaccine (n=12), one dose of vaccine (n=12), or two doses of placebo (n=6), with the dosage selection based on the highest well-tolerated dose in the dose-escalation cohorts (1 - 3), as determined by the SMC. Each of the dose-escalation cohorts (1 - 3) will receive the oral dose of blinded study product while in the inpatient setting. During the following subsequent 96 hours (4 days), participants will remain on the inpatient research isolation ward to be closely monitored, and each stool will be collected by study staff. The evaluation and monitoring of participants enrolled in the fourth cohort will be conducted entirely in the outpatient setting.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
53
Live, attenuated, vaccine strain of S. flexneri 2a expressing CFA/I and LT of enterotoxigenic E. coli
Sodium bicarbonate buffer
University of Maryland, Baltimore, University of Maryland School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, United States
Participants Experiencing Fever, Diarrhea, or Dysentery; Solicited Local Adverse Events; Solicited Systemic Adverse Events; and Clinical Safety Laboratory Adverse Events
Participants experiencing fever, diarrhea, or dysentery; solicited local adverse events; solicited systemic adverse events; and clinical safety laboratory adverse events
Time frame: Solicited AEs: Cohorts 1-3 during 4 days of inpatient and memory aid for another 3 days; Cohort 4 memory aid over 7 days after each dose of study product Clinical Safety Labs: Cohorts 1-3: Day 1 and Day 8; Cohort 4: Days 1 and 29 and Days 8 and 36
Vaccine Organisms Shed in Stools in Cohorts 1-3 - Cohorts 1-3
Vaccine organisms shed in stools in Cohorts 1-3
Time frame: 7 days
Vaccine Organisms Shed in Stools in Cohort 4
Vaccine organisms shed in stools in Cohort 4
Time frame: 2 days
Number of Participants With Genetically Stable Fecal Shed Organisms
Fecal shed organisms found to be genetically stable, as defined as being PCR positive for Shigella (ipaH or virG), CFA/I (cfaB), and LTB (eltB)
Time frame: 7 days
Participants With ELISA Antibody Responses
Seroconversions (defined as 4-fold or higher compared to baseline) in antigen-specific ELISA antibody responses
Time frame: 28 days
Participants With ASC Responses
Responses (defined as ≥8 spot forming cells/10\^6 PBMC) in antigen-specific ASC responses post-vaccination
Time frame: 7 days
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