Inclusion Criteria:
1. Provide informed consent prior to initiation of any study procedures.
2. Are able to understand and comply with planned study procedures and be available for all study visits.
3. Is 18-49 years of age inclusive and in sufficiently good health\* to be safely enrolled in this study as determined by medical history, medication use, and abbreviated physical exam.
\*Good health is defined by the absence of any exclusionary medical conditions. If the subject has another current, ongoing medical condition, the condition cannot meet any of the following criteria: 1) first diagnosed within 3 months of enrollment; 2) is worsening in terms of clinical outcome in last 6 months; or 3) involves need for medication that may pose a risk to subject's safety or impede assessment of adverse events or immunogenicity if they participate in the study. Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria, herbals, vitamins, and supplements are permitted.
4. Oral temperature is less than 100.4 degrees Fahrenheit.
5. Pulse is 50 to 100 beats per minute (bpm), inclusive.
6. Systolic blood pressure is 90 to 140 mmHg, inclusive.
7. Diastolic blood pressure is 55 to 90 mmHg, inclusive.
8. Females of childbearing potential\*\* may enroll if subject has practiced adequate contraception\*\*\* = / \> 30 days prior to enrollment and agrees to continue adequate contraception for the entire study.
\*\*Child-bearing potential is defined as not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \<1 year of the last menses if menopausal.
\*\*\*Adequate contraception includes; non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject enrollment, barrier methods such as condoms or diaphragms with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill").
9. Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment.
10. Drug screen for opiates is negative.
11. BMI (Body Mass Index) between 18 and 40kg/m\^2.
Exclusion Criteria:
1. Have any disease or medical condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation\*\*\*\*.
\*\*\*\* Including acute or chronic disease or medical condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. These include:
1. History of inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, indeterminate colitis, or celiac disease).
2. Irritable bowel syndrome (IBS) within the past 12 months or any active uncontrolled gastrointestinal disorders or diseases as assessed by the investigator. Including: symptoms or evidence of active gastritis or gastroesophageal reflux disease, gastric surgery or gastric acid hyper-secretory disorders (e.g., Zollinger-Ellison syndrome), gastrointestinal obstruction, ileus, gastric retention, bowel perforation, toxic colitis, persistent infectious gastroenteritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection.
3. Known active neoplastic disease (Non-melanoma, treated, skin cancers are permitted), a history of any hematologic malignancy, or have used anticancer chemotherapy/radiation therapy (cytotoxic) within 3 years prior to study enrollment.
4. Personal or family history of reactive arthritis.
5. Reported history of HIV, Hepatitis B, or Hepatitis C
6. History of immunodeficiency due to congenital or hereditary causes, underlying illness or treatment.
2. Positive serology results for HLA-B27, HIV, HBsAg, or HCV antibodies.
3. Have clinically significant abnormalities as determined by study investigator in other screening laboratory tests, as outlined in the protocol.
4. Have participated in a previous Shigella challenge study or reports having received vaccination for Shigella previously.
5. Have a previously laboratory confirmed case of disease caused by S. sonnei or serology positive (\>1:2500) for anti S. sonnei LPS IgG ELISA titer at screening.
6. Has a history of diarrhea in the 14 days prior to enrollment.
7. Have fewer than 3 stools per week or more than 3 stools per day as the usual frequency.
8. Recent history/current use of immunosuppressive/immunomodulating disease therapy.
9. Known hypersensitivity to ciprofloxacin or trimethoprim-sulfamethoxazole; sodium bicarbonate; or any components of vaccine, placebo, or challenge material.
10. Received or plan to receive a licensed live vaccine within 30 days prior to enrollment.
11. Received or plan to receive a licensed, inactivated, Coronavirus disease 2019 (COVID-19) vaccine or an influenza vaccine within +-7 days from receipt of study product.
12. Have a history of severe reactions following previous immunization with any licensed or unlicensed vaccine.
13. Received Ig or other blood products (with exception of Rho D Ig) within 90 days prior to enrollment.
14. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose, or high-dose inhaled corticosteroids\*\*within 30 days prior to enrollment.
\*\* High-dose defined per age as using inhaled high dose per reference chart Estimated Comparative Daily Dosages https://www.nhlbi.nih.gov/files/docs/guidelines/asthma\_qrg.pdf
15. Have taken systemic antibiotics within 7 days prior to enrollment.
16. Have taken prescription and/or OTC medication containing loperamide, acetaminophen, aspirin, ibuprofen, or other non-steroidal anti-inflammatory \< / = 48 hours prior to enrollment.
17. Have a history of alcohol or drug abuse within 1 year prior to enrollment.
18. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to enrollment.
19. Work or plan to work in either a health care setting, day care center, or as a food handler or have known daily contact with individuals with possible increased susceptibility\*\*\*\*\*\* to Shigella within 14 days after discharge from inpatient challenge.
\*\*\*\*\*\* Immunocompromised, elderly persons aged 70 years or more, diapered individuals, persons with disabilities, children \< 2 years old, a woman known to be pregnant or nursing, or anyone with diminished immunity. Known daily contact includes contact at home, school, day-care, nursing home, or similar places.
20. Are pregnant, breastfeeding or plan to become pregnant or breastfeed at any given time during the study.
21. Have fever or an acute illness\*\*\*\*\*\*\* as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to enrollment.
\*\*\*\*\*\*\* An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol
22. Received an experimental agent (including vaccine, drug, biologic, device, blood product, or medication, other than from participation in this trial) within 30 days prior to the first study vaccination or expect to receive an investigational product during the study period which might affect safety or assessment of study endpoints.
23. Taking prescription or over-the-counter medication for weight reduction.
