Shigella WRSS1 Vaccine Trial in Bangladesh

• Sponsor: PATH (Other)
• Overall Status: Completed
• CT.gov ID: NCT02934178
• Collaborator: International Centre for Diarrhoeal Disease Research, Bangladesh (Other)
• Enrollment: 16
• Location: 1
• Arms: 8
• Actual Duration (Months): 10.5
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This is a research study of an experimental (investigational) live attenuated Shigella sonnei vaccine (WRSS1) to find a dose of the vaccine that is safe, tolerable, and develops an immune response. Shigella causes bloody and watery diarrhea, and infants and children living in developing countries experience the greatest consequences of this disease.

Condition or Disease	Intervention/Treatment	Phase
Diarrhea	Biological: Shigella sonnei Strain WRSS1 Vaccine; Biological: Placebo	Phase 1

Detailed Description

The WRSS1 vaccine in will be given to healthy toddlers (12-24 months old). The first vaccination was given to toddlers in the inpatient unit and the second and third doses will be administered on an outpatient basis. A safety evaluation was performed after the first dose before enrolling subjects in subsequent cohorts to receive a higher vaccine dose.

After the study was initiated, its funder, the Bill and Melinda Gates Foundation (BMGF) made significant changes to the PATH Enteric Vaccine Initiative (EVI) portfolio and decided not to support the three higher-dose cohorts (Cohort 1, 2, and 3) planned as part of this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 1 Randomized, Double-Blinded, Placebo-controlled, Dose-Escalation Study to Assess the Safety, Tolerability and Immunogenicity of Live Attenuated, Oral Shigella WRSS1 Vaccine in Bangladeshi Toddlers (12 to 24 Months Old)
• Actual Study Start Date: Feb 23, 2017
• Actual Primary Completion Date: Jan 10, 2018
• Actual Study Completion Date: Jan 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: WRSS1 3 x 10³ CFU Healthy toddlers receiving 3 oral doses of 3 x 10³ colony-forming units (CFU) of Shigella sonnei Strain WRSS1 approximately 4 weeks apart.	Biological: Shigella sonnei Strain WRSS1 Vaccine; Live attenuated, oral Shigella WRSS1 vaccine
Experimental: Cohort 2: WRSS1 3 x 10⁴ CFU Healthy toddlers receiving 3 oral doses of 3 x 10⁴ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart.	Biological: Shigella sonnei Strain WRSS1 Vaccine; Live attenuated, oral Shigella WRSS1 vaccine
Experimental: Cohort 3: WRSS1 3 x 10⁵ CFU Healthy toddlers receiving 3 oral doses of 3 x 10⁵ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart.	Biological: Shigella sonnei Strain WRSS1 Vaccine; Live attenuated, oral Shigella WRSS1 vaccine
Experimental: Cohort 4: WRSS1 3 x 10⁶ CFU Healthy toddlers receiving 3 oral doses of 3 x 10⁶ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart.	Biological: Shigella sonnei Strain WRSS1 Vaccine; Live attenuated, oral Shigella WRSS1 vaccine
Placebo Comparator: Cohort 1: Placebo Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10³ WRSS1 approximately 4 weeks apart.	Biological: Placebo; Sterile saline solution
Placebo Comparator: Cohort 2: Placebo Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁴ WRSS1 approximately 4 weeks apart.	Biological: Placebo; Sterile saline solution
Placebo Comparator: Cohort 3: Placebo Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁵ WRSS1 approximately 4 weeks apart.	Biological: Placebo; Sterile saline solution
Placebo Comparator: Cohort 4: Placebo Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁶ WRSS1 approximately 4 weeks apart.	Biological: Placebo; Sterile saline solution

Outcome Measures

Primary Outcome Measures

1. Maximum Severity of Reactogenicity by Vaccination [72 hours after each vaccination (Day 3, Day 31, Day 59)]

   All toddlers were monitored for evidence of immediate reactions, assessed for systemic reactogenicity (fever, irritability, decreased appetite, and decreased activity) and gastrointestinal (GI) symptoms (abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence, constipation) during the 72 hours following each vaccine dose.

2. Number of Participants With Adverse Events Occurring Within 28 Days After Any Vaccination by Maximum Severity [Up to 28 days after any vaccination (up to Day 84)]

   All toddlers were monitored for the occurrence of any adverse event (AE) or serious adverse event (SAE). Toddlers visited the clinic for safety assessments approximately one month after each vaccination. Grades are based on maximum severity per participant.

Secondary Outcome Measures

1. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens [Days 0, 7, 35, and 63]

   The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgA response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.

2. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen [Days 0, 7, 35, and 63]

   The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei lipopolysaccharide (LPS) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants from cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgA response from circulating lymphocytes.

3. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen [Days 0, 7, 35, and 63]

   The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgG response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.

4. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) [Days 0, 7, 35, and 63]

   The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgG response from circulating lymphocytes.

5. Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen [Days 0, 7, 35, and 63]

   The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgM response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.

6. Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen [Days 0, 7, 35, and 63]

   The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgM response from circulating lymphocytes.

7. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

8. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

9. Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

10. Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

11. Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

12. Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

13. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen [Days 7, 35, and 63]

14. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen [Days 7, 35, and 63]

15. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen [Days 7, 35, and 63]

16. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen [Days 7, 35, and 63]

17. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen [Days 7, 35, and 63]

18. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen [Days 7, 35, and 63]

19. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens [Days 0, 7, 35, and 63]

    The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the enzyme-linked immunosorbent assay (ELISA) plates.

20. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen [Days 0, 7, 35, and 63]

    The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific lipopolysaccharide (LPS) from the Walter Reed Army Institute was used to coat the ELISA plates.

21. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen [Days 0, 7, 35, and 63]

    The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.

22. Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) [Days 0, 7, 35, and 63]

    The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.

23. Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen [Days 0, 7, 35, and 63]

    The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.

24. Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen [Days 0, 7, 35, and 63]

    The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.

25. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

26. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

27. Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

28. Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

29. Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum : Invaplex Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

30. Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63]

31. Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Invaplex Antigen [Days 7, 35, and 63]

32. Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Invaplex Antigen [Days 7, 35, and 63]

33. Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Invaplex Antigen [Days 7, 35, and 63]

34. Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen [Days 7, 35, and 63]

35. Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen [Days 7, 35, and 63]

36. Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen [Days 7, 35, and 63]

37. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen [Days 0, 7, 28, 35, 56, 63, and 84]

    The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei Invaplex in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC.

38. Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen [Days 0, 7, 28, 35, 56, 63, and 84]

    The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei LPS in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84.

39. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigens [Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84]

40. Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen [Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84]

41. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen [Days 7, 28, 35, 56, 63, and 84]

42. Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen [Days 7, 28, 35, 56, 63, and 84]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 24 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Male or female children aged between 12 to 24 month of age at the time of vaccination

2. General good health as determined by the screening evaluation no greater than 30 days before admission

3. Father, mother or other legally acceptable representative (guardian) properly informed about the study, able to understand it and sign the informed consent form

4. Normal bowel habits (< 3 grade 1 or 2 stools each day; ≥ 1 grade 1 or 2 stools every 2 days)

5. Free of obvious health problems as established by medical history and clinical examination before entering into the study.

6. Parent or guardian available for the entire period of the study and reachable by study staff throughout the entire follow-up period.

7. Signed Informed Consent from the Parent or legal guardian

Exclusion Criteria:

1. Presence of a significant medical that in the opinion of the Investigator precludes participation in the study

2. Known infection with human immunodeficiency virus (HIV)

3. Presence in the serum of hepatitis A virus (HAV) or hepatitis C virus (HCV) antibody.

4. History of congenital abdominal disorders, intussusception, abdominal surgery or any other congenital disorder.

5. Participation in research involving another investigational product (defined as receipt of investigational product) 30 days before planned date of first vaccination or concurrently participating in another clinical study, at any time during the study period, in which the child has been or will be exposed to an investigational or a non-investigational product

6. Clinically significant abnormalities on physical examination

7. Clinically significant abnormalities in screening hematology, serum chemistry as determined by the PI or the PI in consultation with the Study Physician

8. History of febrile illness within 48 hours prior to vaccination

9. Known or suspected impairment of immunological function based on medical history and physical examination

10. Prior receipt of any Shigella vaccine

11. Fever at the time of immunization. Fever is defined as a temperature ≥ 37.5C (99.5F) on axillary, oral, or tympanic measurement

12. History of known shigellosis, chronic diarrhea/dysentery in the past 2 months

13. Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazol, OTC agents) or immunosuppressive drug

14. Allergy to quinolone, sulfa, and penicillin classes of antibiotics

15. Clinical evidence of active gastrointestinal illness

16. Prior receipt of a blood transfusion or blood products, including immunoglobulins

17. Presence of any significant systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would endanger the participant's health or is likely to result in non-conformance to the protocol.

18. History of any neurologic disorders or seizures.

19. Acute disease at the time of enrolment

20. Medically significant malnutrition, defined as moderate malnutrition (wt-for-age z-score between -3.0 and -2.0) and severe malnutrition (wt-for-age z-score <-3.0 or edema)

21. Any conditions which, in the opinion of the investigator, might jeopardize the safety of study participants or interfere with the evaluation of the study objectives

22. Receipt of antimicrobial drugs for any reason or a fever ≥ 38C within 7 days before vaccination

23. History of diarrhea during the 7 days before vaccination.

24. Has any household member(s) who is immunocompromised or under the age of 1 year old.

25. Culture or polymerase chain reaction (PCR) positive for any Shigella strain

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mirpur Field Office	Mirpur		Bangladesh

Sponsors and Collaborators

• PATH
• International Centre for Diarrhoeal Disease Research, Bangladesh

Investigators

• Principal Investigator: Rubhana Raqib, MD, International Centre for Diarrhoeal Disease Research, Bangladesh

Study Documents (Full-Text)

• Study Protocol - Jul 10, 2017
• Statistical Analysis Plan - Oct 4, 2018

More Information

Publications

None provided.

• Responsible Party: PATH
• ClinicalTrials.gov Identifier: NCT02934178
• Other Study ID Numbers: VAC-049
• First Posted: Oct 14, 2016
• Last Update Posted: Mar 31, 2020
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by PATH: shigellosis; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases
• Additional relevant MeSH terms: Diarrhea

Study Results

Participant Flow

Recruitment Details	This was a single-site study conducted in Bangladesh. The study originally planned to enroll up to 64 toddlers to receive three doses of 3x10^3, 3x10^4, 3x10^5 or 3x10^6 colony-forming units (CFU) live attenuated, oral shigella WRSS1 vaccine or placebo, however enrollment was terminated after the first dose cohort was enrolled.

Arm/Group Title	Cohort 1: WRSS1 3x10³ CFU	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 approximately 4 weeks apart.
Period Title: Received Vaccination 1
STARTED	12	4
COMPLETED	12	4
NOT COMPLETED	0	0
Period Title: Received Vaccination 1
STARTED	12	4
COMPLETED	12	3
NOT COMPLETED	0	1
Period Title: Received Vaccination 1
STARTED	12	3
COMPLETED	11	3
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo	Total
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ CFU Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.	Total of all reporting groups
Overall Participants	12	4	16
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	17.4 (3.03)	16.0 (1.41)	17.1 (2.74)
Sex: Female, Male (Count of Participants)
Female	6 50%	2 50%	8 50%
Male	6 50%	2 50%	8 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	12 100%	4 100%	16 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	76.0 (4.01)	74.0 (2.16)	75.5 (3.68)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	9.6 (0.92)	9.0 (0.34)	9.4 (0.85)

Outcome Measures

1. Primary Outcome

Title	Maximum Severity of Reactogenicity by Vaccination
Description	All toddlers were monitored for evidence of immediate reactions, assessed for systemic reactogenicity (fever, irritability, decreased appetite, and decreased activity) and gastrointestinal (GI) symptoms (abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence, constipation) during the 72 hours following each vaccine dose.
Time Frame	72 hours after each vaccination (Day 3, Day 31, Day 59)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ CFU Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	12	4
Mild	1 8.3%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	11 91.7%	4 100%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%
Mild	0 0%	1 25%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	3 75%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%
Mild	5 41.7%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	7 58.3%	4 100%
Mild	1 8.3%	1 25%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	11 91.7%	3 75%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%
Mild	0 0%	0 0%
Moderate	0 0%	0 0%
Severe	0 0%	0 0%
Life Threatening	0 0%	0 0%
None	12 100%	4 100%

2. Primary Outcome

Title	Number of Participants With Adverse Events Occurring Within 28 Days After Any Vaccination by Maximum Severity
Description	All toddlers were monitored for the occurrence of any adverse event (AE) or serious adverse event (SAE). Toddlers visited the clinic for safety assessments approximately one month after each vaccination. Grades are based on maximum severity per participant.
Time Frame	Up to 28 days after any vaccination (up to Day 84)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ CFU Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	12	4
Any adverse events: Mild	5 41.7%	3 75%
Any adverse events: Moderate	6 50%	1 25%
Any adverse events: Severe	0 0%	0 0%
Any adverse events: Life Threatening	0 0%	0 0%
Any adverse events: Death	0 0%	0 0%
Any adverse events: Total	11 91.7%	4 100%
AEs related to study vaccine: Mild	0 0%	0 0%
AEs related to study vaccine: Moderate	0 0%	0 0%
AEs related to study vaccine: Severe	0 0%	0 0%
AEs related to study vaccine: Life Threatening	0 0%	0 0%
AEs related to study vaccine: Death	0 0%	0 0%
AEs related to study vaccine: Total	0 0%	0 0%

3. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens
Description	The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgA response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ CFU Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.09	0.07
Day 7	0.07	0.06
Day 35	0.07	0.07
Day 63	0.07	0.07

4. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Description	The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei lipopolysaccharide (LPS) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants from cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgA response from circulating lymphocytes.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.07	0.06
Day 7	0.07	0.07
Day 35	0.07	0.07
Day 63	0.09	0.06

5. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Description	The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgG response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.10	0.15
Day 7	0.15	0.19
Day 35	0.09	0.11
Day 63	0.14	0.12

6. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)
Description	The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgG response from circulating lymphocytes.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.07	0.08
Day 7	0.10	0.08
Day 35	0.07	0.08
Day 63	0.11	0.08

7. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Description	The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgM response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.08	0.10
Day 7	0.14	0.09
Day 35	0.08	0.08
Day 63	0.12	0.09

8. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Description	The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgM response from circulating lymphocytes.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.07	0.09
Day 7	0.13	0.08
Day 35	0.08	0.09
Day 63	0.11	0.11

9. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.01	0.98
Day 35	0.77	1.00
Day 63	0.79	0.96

10. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.00	1.10
Day 35	1.03	1.07
Day 63	1.39	1.04

11. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.45	1.32
Day 35	0.93	0.73
Day 63	1.38	0.82

12. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS)
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.48	1.00
Day 35	1.04	1.07
Day 63	1.58	1.04

13. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.64	0.90
Day 35	0.98	0.78
Day 63	1.39	0.87

14. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.83	0.91
Day 35	1.12	0.93
Day 63	1.58	1.18

15. Secondary Outcome

Title	Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	5 41.7%	1 25%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	8 66.7%	2 50%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	7 58.3%	2 50%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	9 75%	2 50%

16. Secondary Outcome

Title	Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%

17. Secondary Outcome

Title	Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%

18. Secondary Outcome

Title	Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	8 66.7%	1 25%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	2 50%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	2 50%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	2 50%

19. Secondary Outcome

Title	Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%

20. Secondary Outcome

Title	Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	8 66.7%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	8 66.7%	3 75%

21. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens
Description	The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the enzyme-linked immunosorbent assay (ELISA) plates.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.17	0.12
Day 7	0.17	0.10
Day 35	0.16	0.12
Day 63	0.36	0.13

22. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Description	The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific lipopolysaccharide (LPS) from the Walter Reed Army Institute was used to coat the ELISA plates.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.10	0.10
Day 7	0.11	0.09
Day 35	0.09	0.57
Day 63	0.32	0.54

23. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen
Description	The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	66.79	95.23
Day 7	3.76	82.78
Day 35	146.08	119.79
Day 63	29.44	147.73

24. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)
Description	The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	5.02	1.00
Day 7	0.68	0.16
Day 35	14.97	1.03
Day 63	4.63	1.06

25. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen
Description	The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	119.55	107.03
Day 7	177.34	116.79
Day 35	188.41	180.28
Day 63	208.53	198.66

26. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Description	The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates.
Time Frame	Days 0, 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	102.80	108.10
Day 7	146.48	117.38
Day 35	117.25	174.98
Day 63	179.07	148.62

27. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	0.97	0.84
Day 35	0.95	0.98
Day 63	2.18	1.08

28. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.05	0.90
Day 35	0.94	5.47
Day 63	3.18	5.19

29. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	0.06	0.87
Day 35	2.19	1.26
Day 63	0.45	1.55

30. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS)
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	0.13	0.16
Day 35	2.98	1.03
Day 63	0.93	1.06

31. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum : Invaplex Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.48	1.09
Day 35	1.58	1.68
Day 63	1.74	1.86

32. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.43	1.09
Day 35	1.14	1.62
Day 63	1.74	1.37

33. Secondary Outcome

Title	Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Invaplex Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%

34. Secondary Outcome

Title	Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Invaplex Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	3 25%	0 0%
Less than 4-fold rise	8 66.7%	3 75%

35. Secondary Outcome

Title	Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Invaplex Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%

36. Secondary Outcome

Title	Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%

37. Secondary Outcome

Title	Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	2 16.7%	0 0%
Less than 4-fold rise	9 75%	3 75%
4-fold rise or higher	4 33.3%	0 0%
Less than 4-fold rise	7 58.3%	3 75%
4-fold rise or higher	4 33.3%	0 0%
Less than 4-fold rise	7 58.3%	3 75%

38. Secondary Outcome

Title	Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen
Time Frame	Days 7, 35, and 63

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	0 0%	0 0%
Less than 4-fold rise	11 91.7%	3 75%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%
4-fold rise or higher	1 8.3%	0 0%
Less than 4-fold rise	10 83.3%	3 75%

39. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen
Description	The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei Invaplex in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC.
Time Frame	Days 0, 7, 28, 35, 56, 63, and 84

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	0.78	0.48
Day 7	1.74	0.65
Day 28	1.61	1.23
Day 35	1.59	0.61
Day 56	1.12	1.77
Day 63	1.44	1.48
Day 84	0.95	0.52

40. Secondary Outcome

Title	Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen
Description	The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei LPS in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84.
Time Frame	Days 0, 7, 28, 35, 56, 63, and 84

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 0	1.85	0.80
Day 7	3.43	0.58
Day 28	2.99	1.53
Day 35	3.00	0.29
Day 56	2.08	3.51
Day 63	2.05	1.82
Day 84	1.89	0.43

41. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigens
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.88	1.37
Day 28	2.27	2.58
Day 35	1.74	1.28
Day 56	1.44	14.69
Day 63	1.85	3.12
Day 84	1.25	1.10

42. Secondary Outcome

Title	Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen
Time Frame	Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
Day 7	1.84	0.72
Day 28	1.64	1.90
Day 35	1.24	0.36
Day 56	1.14	9.19
Day 63	1.11	2.27
Day 84	0.95	0.53

43. Secondary Outcome

Title	Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen
Time Frame	Days 7, 28, 35, 56, 63, and 84

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	3 25%	1 25%
Less than 4-fold rise	7 58.3%	2 50%
4-fold rise or higher	4 33.3%	1 25%
Less than 4-fold rise	6 50%	2 50%
4-fold rise or higher	3 25%	1 25%
Less than 4-fold rise	7 58.3%	2 50%
4-fold rise or higher	4 33.3%	2 50%
Less than 4-fold rise	7 58.3%	0 0%
4-fold rise or higher	4 33.3%	2 50%
Less than 4-fold rise	7 58.3%	1 25%
4-fold rise or higher	3 25%	2 50%
Less than 4-fold rise	7 58.3%	1 25%
4-fold rise or higher	6 50%	2 50%
Less than 4-fold rise	5 41.7%	1 25%

44. Secondary Outcome

Title	Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen
Time Frame	Days 7, 28, 35, 56, 63, and 84

Outcome Measure Data

Analysis Population Description

Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included.

Arm/Group Title	Cohort 1: WRSS1	Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.	Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
Measure Participants	11	3
4-fold rise or higher	4 33.3%	1 25%
Less than 4-fold rise	6 50%	2 50%
4-fold rise or higher	5 41.7%	1 25%
Less than 4-fold rise	5 41.7%	2 50%
4-fold rise or higher	2 16.7%	1 25%
Less than 4-fold rise	8 66.7%	2 50%
4-fold rise or higher	3 25%	1 25%
Less than 4-fold rise	8 66.7%	1 25%
4-fold rise or higher	3 25%	1 25%
Less than 4-fold rise	8 66.7%	2 50%
4-fold rise or higher	4 33.3%	0 0%
Less than 4-fold rise	6 50%	3 75%
4-fold rise or higher	6 50%	2 50%
Less than 4-fold rise	5 41.7%	1 25%

Adverse Events

Time Frame	Serious adverse events were collected through Day 224. Non-serious adverse events are reported through 28 days after any vaccination (up to Day 84).
Arm/Group Title	Cohort 1: WRSS1		Cohort 1: Placebo
Arm/Group Description	Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart.		Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
All Cause Mortality
	Cohort 1: WRSS1		Cohort 1: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		1/4 (25%)
Serious Adverse Events
	Cohort 1: WRSS1		Cohort 1: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		1/4 (25%)
General disorders
Sudden death	0/12 (0%)		1/4 (25%)
Other (Not Including Serious) Adverse Events
	Cohort 1: WRSS1		Cohort 1: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		4/4 (100%)
Gastrointestinal disorders
Diarrhea	5/12 (41.7%)		2/4 (50%)
Mucous stools	1/12 (8.3%)		0/4 (0%)
Vomiting	1/12 (8.3%)		0/4 (0%)
General disorders
Pyrexia	2/12 (16.7%)		1/4 (25%)
Infections and infestations
Furuncle	2/12 (16.7%)		0/4 (0%)
Gastroenteritis Escherichia coli	0/12 (0%)		1/4 (25%)
Measles	1/12 (8.3%)		0/4 (0%)
Nasopharyngitis	5/12 (41.7%)		0/4 (0%)
Oral candidiasis	0/12 (0%)		1/4 (25%)
Otitis externa	1/12 (8.3%)		0/4 (0%)
Otitis media	1/12 (8.3%)		0/4 (0%)
Otitis media acute	1/12 (8.3%)		0/4 (0%)
Respiratory tract infection	1/12 (8.3%)		1/4 (25%)
Typhoid fever	0/12 (0%)		1/4 (25%)
Upper respiratory tract infection	7/12 (58.3%)		0/4 (0%)
Varicella	1/12 (8.3%)		0/4 (0%)
Nervous system disorders
Febrile convulsion	1/12 (8.3%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/12 (8.3%)		0/4 (0%)
Cough	5/12 (41.7%)		1/4 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.