Trial Outcomes & Findings for A Double-Blind Placebo-Control Dose Escalating Study to Evaluate the Safety and Immunogenicity of dmLT by Oral, Sublingual and Intradermal Vaccination in Adults Residing in an Endemic Area (NCT NCT03548064)

Results Overview

Solicited adverse events were collected post-vaccination and for 7 days after. Local events for the oral route include irritation of the oral cavity or tongue, diarrhea, nausea, vomiting, and abdominal discomfort.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

75 participants

Primary outcome timeframe

Day 1 through Day 8 (post dose 1), Day 15 through Day 22 (post dose 2), Day 29 through Day 36 (post dose 3)

Results posted on

2025-05-21

Participant Flow

Participants were healthy males and non-pregnant females between 18 and 45 years old, inclusively. They were recruited from the community at large around the clinic site. The enrollment period occurred between 10MAR2019 and 11FEB2020.

Participant milestones

Participant milestones
Measure	Oral 5 µg dmLT 5 µg of dmLT administered orally on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Oral 25 µg of dmLT 25 µg of dmLT administered orally on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Oral Placebo Placebo administered orally on Days 1, 15, and 29. Placebo: Sodium bicarbonate buffer is a solution of 2 g sodium bicarbonate in 150 mL of sterile water for injection.	Sublingual 5 µg of dmLT 5 µg of dmLT administered sublingually on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Sublingual 25 µg of dmLT 25 µg of dmLT administered sublingually on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Sublingual Placebo Placebo administered sublingually on Days 1, 15, and 29. Placebo: 0.9% Sodium Chloride, USP (Normal Saline) is a sterile, nonpyrogenic, isotonic solution of sodium chloride 9 mg and may contain hydrochloric acid and/or sodium hydroixde for pH adjustment (pH 5.3, range 4.5 - 7.0).	Intradermal 0.3 µg of dmLT 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Intradermal Placebo Placebo administered intradermally on Days 1, 22, and 43. Placebo: 0.9% Sodium Chloride, USP (Normal Saline) is a sterile, nonpyrogenic, isotonic solution of sodium chloride 9 mg and may contain hydrochloric acid and/or sodium hydroixde for pH adjustment (pH 5.3, range 4.5 - 7.0).
Overall Study STARTED	12	12	6	12	12	6	12	3
Overall Study COMPLETED	12	12	6	11	0	3	12	3
Overall Study NOT COMPLETED	0	0	0	1	12	3	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Sublingual 5 µg of dmLT 5 µg of dmLT administered sublingually on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Sublingual 25 µg of dmLT 25 µg of dmLT administered sublingually on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Sublingual Placebo Placebo administered sublingually on Days 1, 15, and 29. Placebo: 0.9% Sodium Chloride, USP (Normal Saline) is a sterile, nonpyrogenic, isotonic solution of sodium chloride 9 mg and may contain hydrochloric acid and/or sodium hydroixde for pH adjustment (pH 5.3, range 4.5 - 7.0).
Overall Study Withdrawal by Subject	1	0	0
Overall Study Lost to Follow-up	0	2	0
Overall Study Covid-19 Pandemic	0	10	3

Baseline Characteristics

A Double-Blind Placebo-Control Dose Escalating Study to Evaluate the Safety and Immunogenicity of dmLT by Oral, Sublingual and Intradermal Vaccination in Adults Residing in an Endemic Area

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Oral 25 µg of dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29. Placebo: Sodium bicarbonate buffer is a solution of 2 g sodium bicarbonate in 150 mL of sterile water for injection.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Sublingual 25 µg of dmLT n=12 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29. Placebo: 0.9% Sodium Chloride, USP (Normal Saline) is a sterile, nonpyrogenic, isotonic solution of sodium chloride 9 mg and may contain hydrochloric acid and/or sodium hydroixde for pH adjustment (pH 5.3, range 4.5 - 7.0).	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43. Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) enterotoxigenic Escherichia coli (ETEC) Vaccine: LT(R192G/L211A), or dmLT is a derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43. Placebo: 0.9% Sodium Chloride, USP (Normal Saline) is a sterile, nonpyrogenic, isotonic solution of sodium chloride 9 mg and may contain hydrochloric acid and/or sodium hydroixde for pH adjustment (pH 5.3, range 4.5 - 7.0).	Total n=75 Participants Total of all reporting groups
Age, Continuous	30.8 years STANDARD_DEVIATION 6.6 • n=5 Participants	28.8 years STANDARD_DEVIATION 7.0 • n=7 Participants	25.5 years STANDARD_DEVIATION 4.9 • n=5 Participants	27.8 years STANDARD_DEVIATION 7.1 • n=4 Participants	28.8 years STANDARD_DEVIATION 7.4 • n=21 Participants	32.7 years STANDARD_DEVIATION 5.9 • n=10 Participants	31.0 years STANDARD_DEVIATION 7.4 • n=115 Participants	35.0 years STANDARD_DEVIATION 3.6 • n=24 Participants	29.6 years STANDARD_DEVIATION 6.8 • n=42 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	8 Participants n=21 Participants	2 Participants n=10 Participants	6 Participants n=115 Participants	2 Participants n=24 Participants	38 Participants n=42 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=10 Participants	6 Participants n=115 Participants	1 Participants n=24 Participants	37 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	12 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants	12 Participants n=21 Participants	6 Participants n=10 Participants	12 Participants n=115 Participants	3 Participants n=24 Participants	75 Participants n=42 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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	12 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants	12 Participants n=21 Participants	6 Participants n=10 Participants	12 Participants n=115 Participants	3 Participants n=24 Participants	75 Participants n=42 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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) White	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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) More than one race	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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 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	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Region of Enrollment Bangladesh	12 participants n=5 Participants	12 participants n=7 Participants	6 participants n=5 Participants	12 participants n=4 Participants	12 participants n=21 Participants	6 participants n=10 Participants	12 participants n=115 Participants	3 participants n=24 Participants	75 participants n=42 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 8 (post dose 1), Day 15 through Day 22 (post dose 2), Day 29 through Day 36 (post dose 3)

Population: The Safety Analysis population includes all participants who received at least one study vaccination.

Solicited adverse events were collected post-vaccination and for 7 days after. Local events for the oral route include irritation of the oral cavity or tongue, diarrhea, nausea, vomiting, and abdominal discomfort.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo Placebo administered intradermally on Days 1, 22, and 43.
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Irritation of oral cavity or tongue	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Diarrhea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Nausea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Vomiting	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Abdominal discomfort	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · None	12 Participants	12 Participants	6 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Irritation of oral cavity or tongue	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Diarrhea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Nausea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Vomiting	0 Participants	3 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Abdominal discomfort	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · None	12 Participants	9 Participants	6 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Irritation of oral cavity or tongue	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Diarrhea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Nausea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Vomiting	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Abdominal discomfort	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Oral Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · None	11 Participants	12 Participants	6 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 through Day 8 (post dose 1), Day 15 through Day 22 (post dose 2), Day 29 through Day 36 (post dose 3)

Population: The Safety Analysis population includes all participants who received at least one study vaccination.

Solicited adverse events were collected post-vaccination and for 7 days after. Local events for the sublingual route include irritation of the oral cavity or tongue, facial nerve disturbance, diarrhea, nausea, vomiting, or abdominal discomfort.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo Placebo administered intradermally on Days 1, 22, and 43.
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Irritation of oral cavity or tongue	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Facial nerve disturbance	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Diarrhea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Nausea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Vomiting	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Abdominal discomfort	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · None	12 Participants	12 Participants	6 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Irritation of oral cavity or tongue	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Facial nerve disturbance	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Diarrhea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Nausea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Vomiting	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Abdominal discomfort	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Nausea	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Vomiting	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Abdominal discomfort	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · None	12 Participants	10 Participants	6 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · None	12 Participants	10 Participants	6 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Irritation of oral cavity or tongue	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Facial nerve disturbance	0 Participants	0 Participants	0 Participants	—	—	—	—	—
Number of Participants in the Sublingual Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 3 · Diarrhea	0 Participants	0 Participants	0 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 through Day 8 (post dose 1), Day 22 through Day 29 (post dose 2)

Population: The Safety Analysis population includes all participants who received at least one study vaccination.

Solicited adverse events were collected post-vaccination and for 7 days after. Local events for the intradermal route include injection site pain, redness, swelling, bruising, itching, hypo/hyper pigmentation and induration, vesicles, or hardened mass. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=3 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo Placebo administered intradermally on Days 1, 22, and 43.
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site swelling	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site pain	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site redness	2 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site swelling	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site bruising	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site pruritus	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site hypopigmentation	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site hyperpigmentation	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site induration	1 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site vesicles	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · Injection site mass	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 1 · None	9 Participants	3 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site pain	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site redness	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site bruising	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site pruritus	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site hypopigmentation	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site hyperpigmentation	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site induration	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site vesicles	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · Injection site mass	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Local Reactogenicity Events Post Each Dose Post Dose 2 · None	12 Participants	3 Participants	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 through Day 8 (post dose 1), Day 15 through Day 22 (post dose 2), Day 29 through Day 36 (post dose 3)

Population: The Safety Analysis population includes all participants who received at least one study vaccination.

Solicited adverse events were collected post-vaccination and for 7 days after. Systemic events for the oral and sublingual routes include fever, feverishness, fatigue, malaise, myalgia, or headache.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=12 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo Placebo administered intradermally on Days 1, 22, and 43.
Number of Participants in the Oral and Sublingual Arms With Solicited Systemic Reactogenicity Events Post Each Dose Post Dose 1	3 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—	—
Number of Participants in the Oral and Sublingual Arms With Solicited Systemic Reactogenicity Events Post Each Dose Post Dose 2	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—	—
Number of Participants in the Oral and Sublingual Arms With Solicited Systemic Reactogenicity Events Post Each Dose Post Dose 3	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Day 1 through Day 8 (post dose 1), Day 22 through Day 29 (post dose 2)

Population: The Safety Analysis population includes all participants who received at least one study vaccination

Solicited adverse events were collected post-vaccination and for 7 days after. Systemic events for the intradermal route include fever, feverishness, fatigue, malaise, myalgia, headache, diarrhea, nausea, vomiting, or abdominal discomfort. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=3 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo Placebo administered intradermally on Days 1, 22, and 43.
Number of Participants in the Intradermal Arms With Solicited Systemic Reactogenicity Events Post Each Dose Post Dose 1	0 Participants	0 Participants	—	—	—	—	—	—
Number of Participants in the Intradermal Arms With Solicited Systemic Reactogenicity Events Post Each Dose Post Dose 2	0 Participants	0 Participants	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 through Day 209 (Day 223 for Intradermal cohorts)

Population: The Safety Analysis population includes all participants who received at least one study vaccination.

Participants could voluntarily withdraw their consent for study participation for any reason at any time. Primary reason for withdrawal was recorded and early termination visits were attempted.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=12 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Number of Participants Who Withdrew From the Study	0 Participants	0 Participants	0 Participants	1 Participants	12 Participants	3 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 29 (Day 43 for Intradermal cohorts)

Population: The Safety Analysis population includes all participants who received at least one study vaccination.

Participants who received the first vaccination could choose to discontinue receipt of study vaccine for any reason and could choose to remain in the study (i.e., not withdraw from study). In addition, a participant could be discontinued from receipt of the second or third vaccination. Discontinuation from vaccination did not mean automatic withdrawal from the study, and participants were monitored for safety and immunogenicity if the participant consented.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=12 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Number of Participants Who Discontinued Study Vaccination	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	12 Participants	3 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 57 (Day 71 for Intradermal cohorts)

Population: The Safety Analysis population includes all participants who received at least one study vaccination.

Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=12 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Number of Vaccine-related Unsolicited Adverse Events From First Dose Through 28 Days After Last Dose Mild (Grade 1)	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Number of Vaccine-related Unsolicited Adverse Events From First Dose Through 28 Days After Last Dose Severe (Grade 3)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Vaccine-related Unsolicited Adverse Events From First Dose Through 28 Days After Last Dose Moderate (Grade 2)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 209 (Day 223 for Intradermal cohorts)

Population: The Safety Analysis population includes all participants who received at least one study vaccination.

Serious Adverse Events (SAE) were defined as an adverse event which resulted in death, was life threatening, resulted in an inpatient hospitalization, prolongation of an existing hospitalization, led to persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or led to a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalizations were considered serious when, based upon appropriate medical judgment, they jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=12 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Number of Vaccine-related Serious Adverse Events From Post Dose 1 Through 6 Months After Last Dose	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 8 through Day 114

Population: The modified intent-to-treat (mITT) population includes all participants who received at least one study vaccination and contributed both pre- and at least one post-study vaccination.

Blood was collected for the IgA and IgG assay which was conducted with dmLT as the antigen. Each sample was tested per the laboratory's standard operating procedure. The percentage of participants with a \>= 4-fold rise in dmLT-specific serum IgA and IgG titers over baseline was calculated for each study arm from the available results at any time post-first study vaccination. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=10 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgA Titers Over Baseline Measured by ELISA Post-Dose 1 Day 7 (Day 8)	0 percentage of participants Interval 0.0 to 26.5	42 percentage of participants Interval 15.2 to 72.3	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgA Titers Over Baseline Measured by ELISA Pre-Dose 2 (Day 15 oral/sublingual, Day 22 intradermal)	8 percentage of participants Interval 0.2 to 38.5	67 percentage of participants Interval 34.9 to 90.1	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	75 percentage of participants Interval 42.8 to 94.5	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgA Titers Over Baseline Measured by ELISA Post-Dose 2 Day 7 (Day 22 oral/sublingual, Day 29 intradermal)	0 percentage of participants Interval 0.0 to 26.5	83 percentage of participants Interval 51.6 to 97.9	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	83 percentage of participants Interval 51.6 to 97.9	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgA Titers Over Baseline Measured by ELISA Pre-Dose 3 (Day 29 oral/sublingual)	17 percentage of participants Interval 2.1 to 48.4	75 percentage of participants Interval 42.8 to 94.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgA Titers Over Baseline Measured by ELISA Post-Dose 3 Day 7 (Day 36 oral/sublingual)	0 percentage of participants Interval 0.0 to 26.5	67 percentage of participants Interval 34.9 to 90.1	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgA Titers Over Baseline Measured by ELISA Post-Dose 3 Day 28 (Day 57 oral/sublingual)	0 percentage of participants Interval 0.0 to 26.5	33 percentage of participants Interval 9.9 to 65.1	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 28.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgA Titers Over Baseline Measured by ELISA Post-Dose 3 Day 85 (Day 114 oral/sublingual)	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 28.5	—	0 percentage of participants Interval 0.0 to 70.8	—	—

SECONDARY outcome

Timeframe: Day 8 through Day 114

Population: The modified intent-to-treat (mITT) population includes all participants who received at least one study vaccination and contributed both pre- and at least one post-study vaccination.

Blood was collected for the IgG and IgA assay which was conducted with dmLT as the antigen. Each sample was tested per the laboratory's standard operating procedure. The percentage of participants with a \>= 4-fold rise in dmLT-specific serum IgG and IgA titers over baseline was calculated for each study arm from the available results at any time post-first study vaccination. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=10 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgG Titers Over Baseline Measured by ELISA Post-Dose 1 Day 7 (Day 8)	8 percentage of participants Interval 0.2 to 38.5	17 percentage of participants Interval 2.1 to 48.4	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgG Titers Over Baseline Measured by ELISA Pre-Dose 2 (Day 15 oral/sublingual, Day 22 intradermal)	17 percentage of participants Interval 2.1 to 48.4	67 percentage of participants Interval 34.9 to 90.1	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	67 percentage of participants Interval 34.9 to 90.1	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgG Titers Over Baseline Measured by ELISA Post-Dose 2 Day 7 (Day 22 oral/sublingual, Day 29 intradermal)	25 percentage of participants Interval 5.5 to 57.2	83 percentage of participants Interval 51.6 to 97.9	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	20 percentage of participants Interval 2.5 to 55.6	0 percentage of participants Interval 0.0 to 45.9	75 percentage of participants Interval 42.8 to 94.5	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgG Titers Over Baseline Measured by ELISA Post-Dose 3 Day 85 (Day 114 oral/sublingual)	25 percentage of participants Interval 5.5 to 57.2	50 percentage of participants Interval 21.1 to 78.9	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 28.5	—	0 percentage of participants Interval 0.0 to 70.8	—	—
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgG Titers Over Baseline Measured by ELISA Pre-Dose 3 (Day 29 oral/sublingual)	25 percentage of participants Interval 5.5 to 57.2	83 percentage of participants Interval 51.6 to 97.9	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	20 percentage of participants Interval 2.5 to 55.6	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgG Titers Over Baseline Measured by ELISA Post-Dose 3 Day 7 (Day 36 oral/sublingual)	25 percentage of participants Interval 5.5 to 57.2	83 percentage of participants Interval 51.6 to 97.9	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	20 percentage of participants Interval 2.5 to 55.6	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With a >= 4-fold Rise in dmLT-specific Serum IgG Titers Over Baseline Measured by ELISA Post-Dose 3 Day 28 (Day 57 oral/sublingual)	33 percentage of participants Interval 9.9 to 65.1	92 percentage of participants Interval 61.5 to 99.8	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 28.5	20 percentage of participants Interval 2.5 to 55.6	0 percentage of participants Interval 0.0 to 45.9	—	—

SECONDARY outcome

Timeframe: Day 1 through Day 36

Population: The modified intent-to-treat (mITT) population includes all participants who received at least one study vaccination and contributed both pre- and at least one post-study vaccination blood sample for immunogenicity testing for which valid results were reported.

PBMCs were collected for the IgA and IgG assay which was conducted with dmLT as the antigen. Each sample was tested per the laboratory's standard operating procedure. The percentage of participants with \>= 8 dmLT-specific IgA and IgG ASC / 10\^6 PBMC was calculated for each study arm from the available results at any time post-first study vaccination. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=10 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Percentage of Participants With >= 8 dmLT-specific IgA ASC / 10^6 PBMC as Measured by ELISpot Pre-Dose 1 (Day 1)	0 percentage of participants Interval 0.0 to 26.5	8 percentage of participants Interval 0.2 to 38.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 33.6	0 percentage of participants Interval 0.0 to 84.2
Percentage of Participants With >= 8 dmLT-specific IgA ASC / 10^6 PBMC as Measured by ELISpot Pre-Dose 2 (Day 15 oral/sublingual, Day 22 intradermal)	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 8 dmLT-specific IgA ASC / 10^6 PBMC as Measured by ELISpot Post-Dose 2 Day 7 (Day 22 oral/sublingual, Day 29 intradermal)	0 percentage of participants Interval 0.0 to 26.5	8 percentage of participants Interval 0.2 to 38.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	42 percentage of participants Interval 15.2 to 72.3	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 8 dmLT-specific IgA ASC / 10^6 PBMC as Measured by ELISpot Post-Dose 3 Day 7 (Day 36 oral/sublingual)	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With >= 8 dmLT-specific IgA ASC / 10^6 PBMC as Measured by ELISpot Post-Dose 1 Day 7 (Day 8)	0 percentage of participants Interval 0.0 to 26.5	25 percentage of participants Interval 5.5 to 57.2	0 percentage of participants Interval 0.0 to 45.9	8 percentage of participants Interval 0.2 to 38.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	17 percentage of participants Interval 2.1 to 48.4	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 8 dmLT-specific IgA ASC / 10^6 PBMC as Measured by ELISpot Pre-Dose 3 (Day 29 oral/sublingual)	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 30.8	0 percentage of participants Interval 0.0 to 45.9	—	—

SECONDARY outcome

Timeframe: Day 1 through Day 36

Population: The modified intent-to-treat (mITT) population includes all participants who received at least one study vaccination and contributed both pre- and at least one post-study vaccination blood sample for immunogenicity testing for which valid results were reported.

PBMCs were collected for the IgA and IgG assay which was conducted with dmLT as the antigen. Each sample was tested per the laboratory's standard operating procedure. The percentage of participants with \>= 8 dmLT-specific IgA and IgG ASC / 10\^6 PBMC was calculated for each study arm from the available results at any time post-first study vaccination. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=10 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Percentage of Participants With >= 8 dmLT-specific IgG ASC / 10^6 PBMC as Measured by ELISpot Pre-Dose 1 (Day 1)	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 33.6	0 percentage of participants Interval 0.0 to 84.2
Percentage of Participants With >= 8 dmLT-specific IgG ASC / 10^6 PBMC as Measured by ELISpot Post-Dose 1 Day 7 (Day 8)	25 percentage of participants Interval 5.5 to 57.2	58 percentage of participants Interval 27.7 to 84.8	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	20 percentage of participants Interval 2.5 to 55.6	17 percentage of participants Interval 0.4 to 64.1	58 percentage of participants Interval 27.7 to 84.8	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 8 dmLT-specific IgG ASC / 10^6 PBMC as Measured by ELISpot Pre-Dose 2 (Day 15 oral/sublingual, Day 22 intradermal)	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	17 percentage of participants Interval 2.1 to 48.4	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 8 dmLT-specific IgG ASC / 10^6 PBMC as Measured by ELISpot Post-Dose 2 Day 7 (Day 22 oral/sublingual, Day 29 intradermal)	17 percentage of participants Interval 2.1 to 48.4	17 percentage of participants Interval 2.1 to 48.4	0 percentage of participants Interval 0.0 to 45.9	8 percentage of participants Interval 0.2 to 38.5	20 percentage of participants Interval 2.5 to 55.6	0 percentage of participants Interval 0.0 to 45.9	83 percentage of participants Interval 51.6 to 97.9	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 8 dmLT-specific IgG ASC / 10^6 PBMC as Measured by ELISpot Pre-Dose 3 (Day 29 oral/sublingual)	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 45.9	8 percentage of participants Interval 0.2 to 38.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With >= 8 dmLT-specific IgG ASC / 10^6 PBMC as Measured by ELISpot Post-Dose 3 Day 7 (Day 36 oral/sublingual)	8 percentage of participants Interval 0.2 to 38.5	17 percentage of participants Interval 2.1 to 48.4	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	—	—

SECONDARY outcome

Timeframe: Day 1 through Day 36

Population: The modified intent-to-treat (mITT) population includes all participants who received at least one study vaccination and contributed both pre- and at least one post-study vaccination blood sample for immunogenicity testing for which valid results were reported.

Blood was collected for the IgA and IgG assay which was conducted with dmLT as the antigen. Each sample was tested per the laboratory's standard operating procedure. The percentage of participants with a \>= 2-fold rise in ALS anti-dmLT-specific IgG and IgA titers over baseline was calculated for each study arm from the available results at any time post-first study vaccination. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=10 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgA Titers Over Baseline Measured by ELISA Pre-Dose 2 (Day 15 oral/sublingual, Day 22 intradermal)	0 percentage of participants Interval 0.0 to 26.5	17 percentage of participants Interval 2.1 to 48.4	17 percentage of participants Interval 0.4 to 64.1	0 percentage of participants Interval 0.0 to 26.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	58 percentage of participants Interval 27.7 to 84.8	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgA Titers Over Baseline Measured by ELISA Post-Dose 1 Day 7 (Day 8)	75 percentage of participants Interval 42.8 to 94.5	100 percentage of participants Interval 73.5 to 100.0	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	83 percentage of participants Interval 51.6 to 97.9	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgA Titers Over Baseline Measured by ELISA Post-Dose 2 Day 7 (Day 22 oral/sublingual, Day 29 intradermal)	42 percentage of participants Interval 15.2 to 72.3	42 percentage of participants Interval 15.2 to 72.3	0 percentage of participants Interval 0.0 to 45.9	8 percentage of participants Interval 0.2 to 38.5	40 percentage of participants Interval 12.2 to 73.8	17 percentage of participants Interval 0.4 to 64.1	92 percentage of participants Interval 61.5 to 99.8	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgA Titers Over Baseline Measured by ELISA Pre-Dose 3 (Day 29 oral/sublingual)	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 26.5	20 percentage of participants Interval 2.5 to 55.6	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgA Titers Over Baseline Measured by ELISA Post-Dose 3 Day 7 (Day 36 oral/sublingual)	25 percentage of participants Interval 5.5 to 57.2	42 percentage of participants Interval 15.2 to 72.3	0 percentage of participants Interval 0.0 to 45.9	8 percentage of participants Interval 0.2 to 38.5	30 percentage of participants Interval 6.7 to 65.2	17 percentage of participants Interval 0.4 to 64.1	—	—

SECONDARY outcome

Timeframe: Day 1 through Day 36

Population: The modified intent-to-treat (mITT) population includes all participants who received at least one study vaccination and contributed both pre- and at least one post-study vaccination blood sample for immunogenicity testing for which valid results were reported.

Blood was collected for the IgA and IgG assay which was conducted with dmLT as the antigen. Each sample was tested per the laboratory's standard operating procedure. The percentage of participants with a \>= 2-fold rise in ALS anti-dmLT-specific IgG and IgA titers over baseline was calculated for each study arm from the available results at any time post-first study vaccination. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=10 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgG Titers Over Baseline Measured by ELISA Post-Dose 1 Day 7 (Day 8)	67 percentage of participants Interval 34.9 to 90.1	100 percentage of participants Interval 73.5 to 100.0	17 percentage of participants Interval 0.4 to 64.1	8 percentage of participants Interval 0.2 to 38.5	40 percentage of participants Interval 12.2 to 73.8	0 percentage of participants Interval 0.0 to 45.9	100 percentage of participants Interval 73.5 to 100.0	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgG Titers Over Baseline Measured by ELISA Pre-Dose 2 (Day 15 oral/sublingual, Day 22 intradermal)	8 percentage of participants Interval 0.2 to 38.5	75 percentage of participants Interval 42.8 to 94.5	17 percentage of participants Interval 0.4 to 64.1	8 percentage of participants Interval 0.2 to 38.5	20 percentage of participants Interval 2.5 to 55.6	0 percentage of participants Interval 0.0 to 45.9	100 percentage of participants Interval 73.5 to 100.0	33 percentage of participants Interval 0.8 to 90.6
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgG Titers Over Baseline Measured by ELISA Post-Dose 2 Day 7 (Day 22 oral/sublingual, Day 29 intradermal)	50 percentage of participants Interval 21.1 to 78.9	83 percentage of participants Interval 51.6 to 97.9	0 percentage of participants Interval 0.0 to 45.9	25 percentage of participants Interval 5.5 to 57.2	60 percentage of participants Interval 26.2 to 87.8	0 percentage of participants Interval 0.0 to 45.9	100 percentage of participants Interval 73.5 to 100.0	0 percentage of participants Interval 0.0 to 70.8
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgG Titers Over Baseline Measured by ELISA Pre-Dose 3 (Day 29 oral/sublingual)	17 percentage of participants Interval 2.1 to 48.4	42 percentage of participants Interval 15.2 to 72.3	0 percentage of participants Interval 0.0 to 45.9	17 percentage of participants Interval 2.1 to 48.4	10 percentage of participants Interval 0.3 to 44.5	0 percentage of participants Interval 0.0 to 45.9	—	—
Percentage of Participants With >= 2-fold Rise in ALS Anti-dmLT-specific IgG Titers Over Baseline Measured by ELISA Post-Dose 3 Day 7 (Day 36 oral/sublingual)	42 percentage of participants Interval 15.2 to 72.3	58 percentage of participants Interval 27.7 to 84.8	0 percentage of participants Interval 0.0 to 45.9	17 percentage of participants Interval 2.1 to 48.4	30 percentage of participants Interval 6.7 to 65.2	17 percentage of participants Interval 0.4 to 64.1	—	—

SECONDARY outcome

Timeframe: Day 1 through Day 57

Population: The modified intent-to-treat (mITT) population includes all participants who received at least one study vaccination and contributed both pre- and at least one post-study vaccination blood sample for immunogenicity testing for which valid results were reported.

Stool was collected for the IgA assay which was conducted with dmLT as the antigen. Each sample was tested per the laboratory's standard operating procedure. The percentage of participants with a \>= 4-fold rise over baseline in dmLT-specific fecal IgA titers was calculated for each study arm from the available results at any time post-first study vaccination. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.

Outcome measures

Outcome measures
Measure	Oral 5 µg dmLT n=12 Participants 5 µg of dmLT administered orally on Days 1, 15, and 29.	Oral 25 µg dmLT n=12 Participants 25 µg of dmLT administered orally on Days 1, 15, and 29.	Oral Placebo n=6 Participants Placebo administered orally on Days 1, 15, and 29.	Sublingual 5 µg of dmLT n=12 Participants 5 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual 25 µg of dmLT n=10 Participants 25 µg of dmLT administered sublingually on Days 1, 15, and 29.	Sublingual Placebo n=6 Participants Placebo administered sublingually on Days 1, 15, and 29.	Intradermal 0.3 µg of dmLT n=12 Participants 0.3 µg of dmLT administered intradermally on Days 1, 22, and 43.	Intradermal Placebo n=3 Participants Placebo administered intradermally on Days 1, 22, and 43.
Percentage of Participants With >= 4-fold Rise Over Baseline in dmLT-specific Fecal IgA Titers Measured by ELISA Post-Dose 1 Day 7 (Day 8)	0 percentage of participants Interval 0.0 to 26.5	25 percentage of participants Interval 5.5 to 57.2	0 percentage of participants Interval 0.0 to 45.9	17 percentage of participants Interval 2.1 to 48.4	40 percentage of participants Interval 12.2 to 73.8	17 percentage of participants Interval 0.4 to 64.1	8 percentage of participants Interval 0.2 to 38.5	67 percentage of participants Interval 9.4 to 99.2
Percentage of Participants With >= 4-fold Rise Over Baseline in dmLT-specific Fecal IgA Titers Measured by ELISA Pre-Dose 2 (Day 15 oral/sublingual, Day 22 intradermal)	25 percentage of participants Interval 5.5 to 57.2	33 percentage of participants Interval 9.9 to 65.1	17 percentage of participants Interval 0.4 to 64.1	17 percentage of participants Interval 2.1 to 48.4	30 percentage of participants Interval 6.7 to 65.2	33 percentage of participants Interval 4.3 to 77.7	0 percentage of participants Interval 0.0 to 26.5	33 percentage of participants Interval 0.8 to 90.6
Percentage of Participants With >= 4-fold Rise Over Baseline in dmLT-specific Fecal IgA Titers Measured by ELISA Post-Dose 2 Day 7 (Day 22 oral/sublingual, Day 29 intradermal)	8 percentage of participants Interval 0.2 to 38.5	58 percentage of participants Interval 27.7 to 84.8	17 percentage of participants Interval 0.4 to 64.1	8 percentage of participants Interval 0.2 to 38.5	20 percentage of participants Interval 2.5 to 55.6	33 percentage of participants Interval 4.3 to 77.7	0 percentage of participants Interval 0.0 to 26.5	33 percentage of participants Interval 0.8 to 90.6
Percentage of Participants With >= 4-fold Rise Over Baseline in dmLT-specific Fecal IgA Titers Measured by ELISA Pre-Dose 3 (Day 29 oral/sublingual)	25 percentage of participants Interval 5.5 to 57.2	33 percentage of participants Interval 9.9 to 65.1	0 percentage of participants Interval 0.0 to 45.9	8 percentage of participants Interval 0.2 to 38.5	30 percentage of participants Interval 6.7 to 65.2	50 percentage of participants Interval 11.8 to 88.2	—	—
Percentage of Participants With >= 4-fold Rise Over Baseline in dmLT-specific Fecal IgA Titers Measured by ELISA Post-Dose 3 Day 7 (Day 36 oral/sublingual)	25 percentage of participants Interval 5.5 to 57.2	33 percentage of participants Interval 9.9 to 65.1	17 percentage of participants Interval 0.4 to 64.1	8 percentage of participants Interval 0.2 to 38.5	30 percentage of participants Interval 6.7 to 65.2	17 percentage of participants Interval 0.4 to 64.1	—	—
Percentage of Participants With >= 4-fold Rise Over Baseline in dmLT-specific Fecal IgA Titers Measured by ELISA Post-Dose 3 Day 28 (Day 57 oral/sublingual)	25 percentage of participants Interval 5.5 to 57.2	42 percentage of participants Interval 15.2 to 72.3	17 percentage of participants Interval 0.4 to 64.1	27 percentage of participants Interval 6.0 to 61.0	20 percentage of participants Interval 2.5 to 55.6	33 percentage of participants Interval 4.3 to 77.7	—	—

SECONDARY outcome

Timeframe: Day 1 through Day 57

Population: The modified intent-to-treat (mITT) population includes all participants who received at least one study vaccination and contributed both pre- and at least one post-study vaccination blood sample for immunogenicity testing for which valid results were reported.

Saliva was collected for the IgA assay which was conducted with dmLT as the antigen. Each sample was tested per the laboratory's standard operating procedure. The percentage of participants with a \>= 4-fold rise over baseline in dmLT-specific salivary IgA titers was calculated for each study arm from the available results at any time post-first study vaccination. Study halted on Day 43 due to COVID-19 pandemic and the intradermal group did not receive the final dose.