Trial Outcomes & Findings for Dose-Finding Study of Lyophilized Shigella Sonnei 53G Challenge Strain (NCT NCT02816346)

Last Updated: 2019-06-03

Results Overview

Per protocol definition: shedding of S. sonnei in the stool accompanied by moderate-severe diarrhea (4 or more loose/watery Grade 3-5 stools or 400+ gram stools per 24 hours, or requires medical intervention) and/or dysentery (a Grade 3, 4, or 5 stool with gross blood on at least 2 occasions and reportable constitutional symptoms) along with moderate fever (Oral temperature of ≥101.2°F) or one or more severe intestinal symptoms. Alternative endpoint 1 definition: severe diarrhea, or moderate diarrhea plus fever, or moderate diarrhea plus 1 moderate constitutional/enteric symptom, or dysentery. Alternative endpoint 2 definition: severe diarrhea, or moderate diarrhea plus fever, or moderate diarrhea plus 1 severe constitutional/enteric symptom, or dysentery plus 1 severe constitutional/enteric symptom

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

56 participants

Primary outcome timeframe

11 days after administration of S. sonnei

Results posted on

2019-06-03

Participant Flow

Subjects were recruited from the recruiting range of Cincinnati Children's Hospital Medical Center (CCHMC) via word of mouth and advertisements in multiple formats including but not limited to newspapers, fliers, e-mails, and the CCHMC website.

Participant milestones

Participant milestones
Measure	Cohort 1: S. Sonnei 53G Target Dose 500 CFU Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Target Dose: 500cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 2: S. Sonnei 53G Target Dose 1000 CFU Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 1 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Dose: 1000 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 3: S. Sonnei 53G Target Dose of 1000 CFU Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 2 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Dose: 1000 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 4: S. Sonnei 53G Target Dose 1500 CFU Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 3 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Dose: 1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 5: S. Sonnei 53G Target Dose 1150 CFU Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 4 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: One dose of Shigella sonnei rehydrated challenge strain 53G (Lot 1794) suspension in 2 mL of cold sterile water combined and diluted in cold, sterile normal saline 0.9% (i.e. challenge suspension). Mode of Administration: After a 90 minute fast subjects will drink the 120 mL of sodium bicarbonate (to neutralize gastric acidity) and then drink the challenge suspension within 5 minutes. Dose: 1150 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Overall Study STARTED	10	10	10	10	16
Overall Study COMPLETED	10	10	10	10	16
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dose-Finding Study of Lyophilized Shigella Sonnei 53G Challenge Strain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=10 Participants Received 500 colony-forming units (CFU) of Shigella sonnei 53G. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 2 n=10 Participants Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 1 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 3 n=10 Participants Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 2 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 4 n=10 Participants Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 3 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 5 n=16 Participants Received higher dose of Shigella sonnei 53G if ≥ 60% of subjects in Cohort 4 experienced shigellosis, or lower dose if not. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Total n=56 Participants Total of all reporting groups
Age, Continuous	35.7 years STANDARD_DEVIATION 10.7 • n=5 Participants	32.3 years STANDARD_DEVIATION 9.9 • n=7 Participants	34.3 years STANDARD_DEVIATION 9.9 • n=5 Participants	32.2 years STANDARD_DEVIATION 8.8 • n=4 Participants	30.1 years STANDARD_DEVIATION 8.8 • n=21 Participants	32.6 years STANDARD_DEVIATION 9.2 • n=10 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	10 Participants n=21 Participants	33 Participants n=10 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants	23 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	16 Participants n=21 Participants	55 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	14 Participants n=21 Participants	52 Participants n=10 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: 11 days after administration of S. sonnei

Outcome measures

Outcome measures
Measure	Cohort 1 n=10 Participants Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 2 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 3 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 4 n=10 Participants Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 5 n=16 Participants Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Number of Participants With Shigellosis Per protocol definition · Yes	0 Participants	2 Participants	1 Participants	4 Participants	2 Participants
Number of Participants With Shigellosis Per protocol definition · No	10 Participants	8 Participants	9 Participants	6 Participants	14 Participants
Number of Participants With Shigellosis Alternative endpoint 1 · Yes	0 Participants	6 Participants	4 Participants	7 Participants	7 Participants
Number of Participants With Shigellosis Alternative endpoint 1 · No	10 Participants	4 Participants	6 Participants	3 Participants	9 Participants
Number of Participants With Shigellosis Alternative endpoint 2 · Yes	0 Participants	5 Participants	3 Participants	6 Participants	7 Participants
Number of Participants With Shigellosis Alternative endpoint 2 · No	10 Participants	5 Participants	7 Participants	4 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline (days -5,-1), Day 3, Day 7, and Day 14

Population: Stool samples were not collected from all subjects at all time points. Samples containing less than 2 ug/mL of total IgA were excluded from analysis. If both baseline samples were below 2 ug/mL, the subject was excluded from analysis.

IgA (total and S. sonnei specific) will be determined in fecal extracts using standard ELISA. IgA was recovered from stool samples using a soybean trypsin inhibitor ethylenediaminetetraacetic acid (EDTA) procedure. The shigella-antigen specific activity was calculated by dividing the endpoint titer by the IgA concentration in matched samples.

Outcome measures

Outcome measures
Measure	Cohort 1 n=10 Participants Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 2 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 3 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 4 n=10 Participants Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 5 n=16 Participants Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen Baseline 1 (Day -5)	19 titer Standard Deviation 130	11 titer Standard Deviation 8	11 titer Standard Deviation 24	17 titer Standard Deviation 157	8 titer Standard Deviation 6
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen Baseline 2 (Day -1)	15 titer Standard Deviation 53	8 titer Standard Deviation 26	11 titer Standard Deviation 51	9 titer Standard Deviation 200	10 titer Standard Deviation 15
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen Day 3	15 titer Standard Deviation 65	11 titer Standard Deviation 14	9 titer Standard Deviation 11	11 titer Standard Deviation 99	11 titer Standard Deviation 21
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen Day 7	49 titer Standard Deviation 121	70 titer Standard Deviation 413	80 titer Standard Deviation 136	49 titer Standard Deviation 296	42 titer Standard Deviation 155
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen Day 14	211 titer Standard Deviation 1024	40 titer Standard Deviation 841	226 titer Standard Deviation 371	101 titer Standard Deviation 205	57 titer Standard Deviation 431

SECONDARY outcome

Timeframe: Baseline (days -5,-1), Day 3, Day 7, and Day 14

IgA (total and S. sonnei specific) will be determined in fecal extracts using standard ELISA. IgA was recovered from stool samples using a soybean trypsin inhibitor-EDTA procedure. The shigella-antigen specific activity was calculated by dividing the endpoint titer by the IgA concentration in matched samples.

Outcome measures

Outcome measures
Measure	Cohort 1 n=10 Participants Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 2 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 3 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 4 n=10 Participants Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 5 n=16 Participants Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen Baseline 1 (Day -5)	20 titer Standard Deviation 211	18 titer Standard Deviation 60	10 titer Standard Deviation 104	20 titer Standard Deviation 638	11 titer Standard Deviation 22
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen Baseline 2 (Day -1)	19 titer Standard Deviation 130	12 titer Standard Deviation 111	9 titer Standard Deviation 105	10 titer Standard Deviation 403	9 titer Standard Deviation 11
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen Day 3	19 titer Standard Deviation 130	15 titer Standard Deviation 98	6 titer Standard Deviation 2	16 titer Standard Deviation 400	80 titer Standard Deviation 441
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen Day 7	53 titer Standard Deviation 140	92 titer Standard Deviation 381	50 titer Standard Deviation 124	80 titer Standard Deviation 441	84 titer Standard Deviation 498
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen Day 14	422 titer Standard Deviation 3317	118 titer Standard Deviation 1679	320 titer Standard Deviation 459	403 titer Standard Deviation 540	104 titer Standard Deviation 478

SECONDARY outcome

Timeframe: 57 days

Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure	Cohort 1 n=10 Participants Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 2 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 3 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 4 n=10 Participants Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 5 n=16 Participants Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Baseline (Day -1)	528 titer Standard Deviation 611	492 titer Standard Deviation 547	246 titer Standard Deviation 450	459 titer Standard Deviation 420	497 titer Standard Deviation 3137
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Day 7	746 titer Standard Deviation 913	919 titer Standard Deviation 3813	400 titer Standard Deviation 458	857 titer Standard Deviation 1315	951 titer Standard Deviation 6276
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Day 14	4222 titer Standard Deviation 19953	2425 titer Standard Deviation 7591	6859 titer Standard Deviation 15472	3676 titer Standard Deviation 9816	3200 titer Standard Deviation 17160
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Day 28	2425 titer Standard Deviation 15506	1715 titer Standard Deviation 8165	3430 titer Standard Deviation 15370	1715 titer Standard Deviation 4974	1532 titer Standard Deviation 6991
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Day 56	1393 titer Standard Deviation 3897	1131 titer Standard Deviation 8350	1372 titer Standard Deviation 2418	1300 titer Standard Deviation 4188	1131 titer Standard Deviation 12550

SECONDARY outcome

Timeframe: 57 days

Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure	Cohort 1 n=10 Participants Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 2 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 3 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 4 n=10 Participants Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 5 n=16 Participants Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Baseline (Day -1)	373 titer Standard Deviation 666	264 titer Standard Deviation 610	123 titer Standard Deviation 138	348 titer Standard Deviation 2073	248 titer Standard Deviation 823
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Day 7	528 titer Standard Deviation 611	1213 titer Standard Deviation 10390	264 titer Standard Deviation 344	919 titer Standard Deviation 2474	1037 titer Standard Deviation 3047
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Day 14	4222 titer Standard Deviation 16541	2425 titer Standard Deviation 10086	3200 titer Standard Deviation 9864	2111 titer Standard Deviation 7898	3644 titer Standard Deviation 10457
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Day 28	2425 titer Standard Deviation 15598	857 titer Standard Deviation 5990	919 titer Standard Deviation 2444	919 titer Standard Deviation 4032	1288 titer Standard Deviation 4164
Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen Day 56	919 titer Standard Deviation 877	528 titer Standard Deviation 1212	635 titer Standard Deviation 1219	800 titer Standard Deviation 2532	591 titer Standard Deviation 1784

SECONDARY outcome

Timeframe: 57 days

Population: No sample was available for one subject in Cohort 3 on Day 56.

Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure	Cohort 1 n=10 Participants Received target dose of 500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 510, 717, 588, and 567 CFU). Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 2 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 817 CFU), since the attack rate of shigellosis for Cohort 1 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 3 n=10 Participants Received target dose of 1000 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 913 CFU. Although the target dose was the same as Cohort 2, the safety monitoring committee felt that the per-protocol a priori definition of shigellosis was too restrictive and that increasing the dose above 1000 CFU may lead to unnecessarily high toxicity. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 4 n=10 Participants Received target dose of 1500 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) since the attack rate of shigellosis for Cohort 2 and 3 was below the protocol target of 60%. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)	Cohort 5 n=16 Participants Received target dose of 1150 colony-forming units (CFU) of Shigella sonnei 53G (actual dose: 1760 CFU) as the final confirmatory cohort since it was felt that the disease rate and profile of Cohort 4 was appropriate. Shigella sonnei 53G: Investigational Product: Shigella sonnei strain 53G (Lot 1794) Mode of Administration: Delivered with sodium bicarbonate orally after a 90 minute fast. Dose: 500-1500 cfu (doses were to be increased or lowered based on results of preceding cohorts)
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen Baseline (Day -1)	2599 titer Standard Deviation 5412	2599 titer Standard Deviation 1960	2986 titer Standard Deviation 15270	2263 titer Standard Deviation 4011	1745 titer Standard Deviation 12365
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen Day 7	3430 titer Standard Deviation 7619	3940 titer Standard Deviation 4221	3200 titer Standard Deviation 7303	3940 titer Standard Deviation 3477	3490 titer Standard Deviation 24798
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen Day 14	10397 titer Standard Deviation 31301	7352 titer Standard Deviation 30508	14703 titer Standard Deviation 14347	11143 titer Standard Deviation 18203	8300 titer Standard Deviation 28740
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen Day 28	9701 titer Standard Deviation 18863	6859 titer Standard Deviation 14595	11943 titer Standard Deviation 14904	9701 titer Standard Deviation 9361	6683 titer Standard Deviation 33105
Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen Day 56	6400 titer Standard Deviation 9199	4525 titer Standard Deviation 7013	10159 titer Standard Deviation 9659	5971 titer Standard Deviation 4758	4525 titer Standard Deviation 16370

SECONDARY outcome

Timeframe: 57 days

Population: No sample was available for one subject in Cohort 3 on Day 56.

Blood (10 mL) was collected on days -1, 7, 14, 28 and 56 for Immunoglobulin A (IgA), Immunoglobulin M (IgM), and Immunoglobulin G (IgG) assay by Enzyme linked immunosorbent assay (ELISA).