A Phase 1 dose escalating study of ETEC candidate vaccine to determine safety and
immunogenicity of a multi-dose regimen in healthy adult volunteers. The study will be
conducted at Cincinnati Children's Hospital Medical Center (CCHMC). The primary objectives
assess the safety and tolerability of dmLT vaccine when administered in three doses
sublingually over a range of dosages in healthy adult subjects. The secondary objectives
assess long-term safety follow-up from immunization through Month 7 post vaccination,
following three SL doses of dmLT vaccine over a range of dosages and comparing with three
doses of a comparable dosage of oral vaccine. The study subject population is 52 healthy
adult male and female subjects, ages 18 to 45. Subject participation duration is
approximately 8 months with study duration of approximately 1.5-2 years, including 6-7 months
of follow-up.
Primary Outcomes
Measure: Occurrence of solicited reactogenic side effects through Day 8 following each vaccination. Time: Day 0 to Day 8
Measure: Occurrence of vaccine-related, non-solicited adverse events (AEs) for facial nerve disturbance through 75 days post third vaccination. Time: Day 29 through Day 104
Measure: Occurrence of vaccine-related, non-solicited adverse events (AEs) through Day 36 following first vaccination. Time: Day 0 to Day 36
Secondary Outcomes
Measure: Occurrence of vaccine-related serious adverse events (SAEs) through 7 months following first vaccination. Time: Day 0 through Day 210
Measure: Proportion of subjects with =4-fold rise from the baseline in LT toxin neutralization titers. Time: Days 0, 8, 15, 22, 29, 36, 64 and 85
Measure: Proportion of subjects with >/= 2-fold rise from the baseline in dmLT-specific IgA- and IgG-ALS at any time after vaccination. Time: Days 0, 8, 15, 22, 29, 36, 64, and 85
Measure: Proportion of subjects with >/= 4-fold rise from the baseline in dmLT-specific fecal IgA or >/= 4-fold rise for the ratio of specific over total IgA after vaccination. Time: Days 0, 8, 15, 22, 29, 36, and 64
Measure: Proportion of subjects with >/= 4-fold rise from the baseline in dmLT-specific IgA- and IgG-ALS after vaccination. Time: Days 0, 8, 15, 20, 22, 29, 34, and 36
Measure: Proportion of subjects with >/= 4-fold rise from the baseline in dmLT-specific saliva IgA or >/= 4-fold rise for the ratio of specific over total IgA after vaccination. Time: Days 0, 8, 15, 22, 29, 36, and 64
Measure: Proportion of subjects with >/= 4-fold rise from the baseline in dmLT-specific serum IgA or IgG at any time after vaccination. Time: Days 0, 8, 15, 22, 29, 36, 64, and 85
Measure: Proportion of subjects with >8 IgA- or IgG-ASC/10^6 peripheral blood mononuclear cells (PBMCs) after vaccination. Time: Days 0, 8, 15, 20, 22, 29, 34, and 36
Measure: Proportion of subjects with IgG and IgA dmLT-specific circulating ASC expressing gut homing receptors. Time: Days 0 8, 15, 20, 22, 29, 34, and 36