Inclusion Criteria:
1. Non-pregnant, non-breast-feeding adults, age 18 to 49 years (inclusive) at the time of enrollment.
2. Willing and able to sign and date informed consent document prior to study procedures.
3. Stated willingness to be available for all study visits and comply with all trial procedures throughout the duration of the trial, including adherence to Lifestyle Considerations.
4. Participants of childbearing potential must have a negative pregnancy test at study enrollment.
5. For participants of childbearing potential\*: agree to use highly effective contraception with heterosexual intercourse for at least 1 month prior to the first vaccination through at least two months after receipt of the challenge agent or last dose of study product if not challenged. True abstinence is also acceptable.
* Childbearing potential in a participant assigned female at birth 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.
* Acceptable forms of highly effective contraception for participants assigned female at birth include same sex 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 participant 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"). Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.
6. Body mass index (BMI) 19 to less than 40 kg/m\^2 at screening.
7. In good health. As determined by medical history and physical examination to evaluate acute or ongoing chronic medical diagnoses/conditions that have been present for at least 90 days, which would affect the assessment of safety of participants and interpretations of the scientific aims of the trial. Chronic medical diagnoses/conditions should be stable for the last 60 days (no hospitalizations, ER, or urgent care for condition or need for supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis/condition in the 60 days before enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the Principal or sub-Investigator licensed to make medical diagnosis, will not be considered a deviation of this inclusion criterion. Participants may be on chronic or as needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening of medical diagnosis/condition. Similarly, medication changes subsequent to enrollment and trial vaccination are acceptable provided the change was not precipitated by deterioration in the chronic medical condition, and there is no anticipated additional risk to the participant or interference with the evaluation of responses to trial vaccination.
8. Oral temperature is less than 100.4 degrees Fahrenheit (38 degrees Celsius) at the time of enrollment.
9. Heart rate (HR) 60 to 100 beats per minute, inclusive. If participant baseline HR is between 50 and 60 beats per minute and the Principal or sub-Investigator licensed to make medical diagnosis determines that this is not clinically significant (e.g., if they are known to be high intensity athletes, have no clinical symptoms associated with the bradycardia, and have no signs or symptoms of other diseases causing bradycardia), this will NOT be considered a grade 1 adverse event and the participant still will be eligible.
10. Blood pressure (BP):systolic BP \>/= 90 to \</= 140 mm Hg; diastolic BP \>/=55 to \</=90 mmHg.
11. Must agree to refrain from donating blood or plasma (outside of this trial) from the first dose of study product until at least 30 days after completion of inpatient portion of the trial or last day of study product if not challenged.
Exclusion Criteria:
1. Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis.
2. History of microbiologically confirmed ETEC or cholera infection in the last 3 years.
3. Symptoms consistent with MSD concurrent with travel to countries where ETEC infection is endemic (refer to MOP section for a list of endemic countries) within 3 years prior to enrollment.
4. Vaccination for, ingestion of or occupational handling of ETEC, cholera, or E. coli heat labile toxin within 3 years prior to enrollment.
5. Any condition that, in the judgment of the investigator, precludes participation because it could affect participant safety or endpoint evaluation.
6. Unable to understand spoken and written English.
7. Venous access deemed inadequate for phlebotomy/cannulation needs of the study.
8. Have any disease or medical condition that, in the opinion of the Principal or sub-Investigator licensed to make medical diagnosis, is a contraindication to study participation. These include:
* History within the past 12 months of inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, indeterminate colitis, or celiac disease), irritable bowel syndrome (IBS), or any active uncontrolled gastrointestinal disorders or diseases as assessed by the investigator.
* Within the past 12 months have symptoms or evidence of active gastritis or severe gastroesophageal reflux disease not well controlled on medication, 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.
9. 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.
10. Positive serology results for HIV Ag/Ab combo, HBsAg, or HCV Ab.
11. Serum IgA \<40 mg/dL
12. History of immunodeficiency due to congenital or hereditary causes, underlying illness, or treatment
13. Have screening labs that are greater than Grade 1 severity. Values below the lower limit of normal for creatinine, bilirubin and/or ALT are acceptable for study inclusion as they are not considered to be clinically significant by the Principal or sub-Investigator licensed to make medical diagnosis.
14. Within the past 3 years have participated in an ETEC challenge study or reports having received vaccination for ETEC.
15. Use of immunosuppressive/immunomodulating disease therapy within 1 year of 1st dose of study vaccine.
16. Planning to receive Ig or other blood products (with exception of Rho D Ig) from 90 days before 1st vaccination until 30 days after receipt of challenge agent or last day of study product if not challenged.
17. Received systemic antibiotics\* within 7 days prior to receipt of study vaccine.
\*Including Quinolones, nitrofurantoin, nalidixic acid, chloramphenicol, Quinine, chloroquine, primaquine.
18. Took prescription or OTC medication containing loperamide, acetaminophen, aspirin, ibuprofen, or other non-steroidal anti-inflammatory within 24 hours of receipt of vaccine.
19. Planning to receive an investigational agent or product\* within 30 days prior to the first study vaccination through 60 days after last dose of study vaccine.
\*Including vaccine, drug, biologic, device, blood product, or medication, other than from participation in this trial.
20. Planning to receive a licensed, live vaccine within 30 days before or after each vaccination.
21. Planning to receive a licensed, inactivated vaccine\* within 14 days before or after each vaccination: \*An exception is a COVID and/or influenza vaccine which may be received within 7 days of vaccination and still be eligible.
22. Within 14 days prior to vaccination, have completed a course of oral or parenteral\* corticosteroids of any dose for 5 or more days, or high dose\*\* inhaled corticosteroids.
\* Including intra-articular
\*\*High dose defined per guideline; https://www.nhlbi.nih.gov/files/docs/guidelines/asthma\_qrg.pdf
23. Known hypersensitivity to both ciprofloxacin and trimethoprim-sulfamethoxazole; sodium bicarbonate; or any components of vaccine, placebo, or challenge material.
24. Have a history of severe reactions following previous immunization with any licensed or unlicensed vaccine.
25. Have a history of alcohol or drug abuse within 1 year prior to enrollment.
26. Positive urine toxicology screen for opiates
27. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 3 years prior to enrollment.
28. Taking or have taken prescription or over-the-counter medication for weight reduction 3 months before enrollment through the completion of the challenge phase.
29. Within 7 days after discharge from the challenge unit plan to work in either a patient care setting, day care center, or as a food handler.
30. Plan to have daily contact with individuals with possible increased susceptibility\* to severe ETEC infection\* in the week after discharge from the inpatient challenge unit.
\* Increased susceptibility to severe ETEC infection including; 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.
31. History of prolonged QT syndrome and/or torsade de pointes or in those with risk factors for QT syndrome, such as currently receiving Class IA or Class III antiarrhythmic agents, tricyclic antidepressants, or antipsychotics.
32. Currently known to have a folate deficiency, or a history of glucose-6-phosphate dehydrogenase deficiency.
