Inclusion Criteria:
Step 1 and Step 2:
1. Age 18-50 years (inclusive).
2. In good health and stable medical condition, determined by MH, laboratory results, and physical examination during screening period.
3. Negative pregnancy test at the time of 1st injection, for participants of childbearing potential.
4. Persons of childbearing potential must agree to avoid pregnancy by use of effective contraception for 30 days prior to 1st injection and throughout the study. Participants assigned female at birth and unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).
5. Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
6. Availability for the study duration, including all planned follow-up visits and phone calls.
7. Willingness to refrain from participating in other studies of investigational products until completion of the last study contact.
Step 2 only:
8. Demonstrated comprehension of the protocol procedures, knowledge of Shigella- associated illness, and passing score of 70% or better on a comprehension assessment. Maximum two attempts are allowed.
Exclusion Criteria:
Step 1 and Step 2:
1. Participants currently pregnant, lactating, or intending to become pregnant during the study period as reported by the participant.
2. Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study.
3. Clinically significant abnormalities in vital signs or in screening hematology / blood chemistry as determined by the investigator.
4. Presence in the serum of HIV 1/2 antibody, HBs-Ag, or HCV antibody (if confirmed positive by Hepatitis C confirmatory test, i.e., recombinant immunoblot assay (RIBA), polymerase chain reaction (PCR)).
5. Evidence of current excessive alcohol consumption or drug dependence (e.g. according to medical history).
6. Known or suspected impairment of immunological function (e.g., documented HIV infection, asplenia/splenectomy, or history of autoimmune disease or lymphoproliferative disorder).
7. BMI \< 19 or \> 35 kg/m2.
8. Recent vaccination or planned vaccination within 14 days of 1st study injection for inactivated vaccines and within 30 days for live vaccines.
9. Recent receipt of an investigational product within 30 days preceding the 1st study injection or planned during the entire study period.
10. Recent treatment with immunoglobulins or blood products within 3 months preceding the 1st study injection or planned use during the entire study period.
11. Use of any medication known to affect the immune function (e.g., systemic steroids) within 30 days preceding the 1st study injection or planned use during the entire study period.
12. Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where Shigella infection is endemic (most of the developing world).
13. Vaccination for or ingestion of Shigella.
14. Use of systemic antibiotics during the 7 days before 1st injection.
15. Serum IgG titers to S. sonnei LPS ≥ 2500.
16. Current occupation involving the handling of Shigella bacteria.
17. History of allergy to components of the study vaccine (Alhydrogel), to placebo (PBS), or to soy, or any other allergy the investigator deems to increase their risk of AEs in the study.
18. Any other criteria which, in the investigator's opinion, would compromise the ability of the participant to participate in the study, the safety of the study, or the results of the study.
19. Part of study personnel or close family member of personnel conducting the study.
Step 2 only:
20. Personal history of inflammatory ReA.
21. Positive blood test for HLA-B27 antigen.
22. Personal history of IBS as defined by Rome IV criteria.
23. Regularly abnormal stool pattern (fewer than 3 per week or more than 3 per day).
24. Regular use of laxatives, antacids, or other agents to lower stomach acidity.
25. Known allergy to challenge agent components.
26. Known allergy to ciprofloxacin or trimethoprim-sulfamethoxazole.
27. Evidence of IgA deficiency (serum IgA \< 7 mg/dL or limit of detection of assay).
28. Planning to travel to Shigella endemic countries before completion of the challenge phase of the study.
29. Personal history of inflammatory bowel disease.
