Shigella Sonnei 53G Human Infection Study in Kenyan Adults

Inclusion Criteria:

• Healthy adults between 18 and 45 years of age (inclusive) Kilifi County residents

• Able and willing (in the Investigator's opinion) to comply with all studyrequirements.

• Provide informed consent.

• Demonstrate comprehension of the protocol procedures and knowledge of study bypassing a test of understanding (pass grade 100%).

• Use of effective method of contraception for the entire duration of study (prior tostudy start and up to study completion) (women only). Female volunteers will beasked to provide their family planning records to verify. Effective contraception isdefined as a contraceptive method with failure rate of less than 1% per year whenused consistently and correctly, in accordance with the product label. Examples ofthese include: combined oral contraceptives; injectable progestogen; implants ofetenogestrel or levonorgestrel; intrauterine device or intrauterine system; malepartner sterilisation at least 6 months prior to the female volunteer's entry intothe study, and the relationship is monogamous; male condom combined with a vaginalspermicide (foam, gel, film, cream or suppository); and male condom combined with afemale diaphragm, either with or without a vaginal spermicide (foam, gel, film,cream, or suppository).

• Willingness to participate for an inpatient stay lasting approximately 12 days orlonger and an outpatient follow-up lasting about 12 months from challenge.

• Available for all planned follow-up visits.

Exclusion Criteria:

• Presence of a significant medical condition (e.g., psychiatric conditions, alcoholor illicit drug abuse/dependency, or gastrointestinal disease, such as peptic ulcer,symptoms or evidence of active gastritis or gastroesophageal reflux disease,inflammatory bowel disease), or other laboratory abnormalities which in the opinionof the investigator precludes participation in the study.

• Known immunosuppressive illness for example those with cancer, on immunosuppressivetherapy, HIV etc.

• Positive serology results for HIV, HBsAg, or HCV antibodies.

• Evidence of inflammatory arthritis on exam and/or HLA-B27 positive.

• Family history of inflammatory arthritis.

• Clinically significant abnormalities in screening lab haematology or serumchemistry, as determined by PI or PI in consultation with the research monitor andSponsor.

• Known allergies to fluoroquinolones, β-lactams or trimethoprim-sulfamethoxazole (anyof the three are exclusionary).

• Fewer than 3 stools per week or more than 3 stools per day as the usual frequency.

• History of diarrhoea in the 2 weeks prior to planned inpatient phase.

• Use of antibiotics during the 7 days before receiving the challenge inoculum dosing.

• Use of prescription and/or OTC medications that contain imodium, acetaminophen,aspirin, ibuprofen, and/or other non-steroidal anti-inflammatory drugs, during the 48 hours prior to investigational product administration.

• Confirmed PCR positive for SARS-COV-2 three days before challenge i.e., Day -3.

• Use of any medication known to affect the immune function within 30 days precedingreceipt of the challenge inoculum or planned use during the active study period.

• Serologic evidence of prior S. sonnei infection as determined by ELISA.

• A chronic disease for which doses of prescription medications are not stable for atleast the past 3 months.

• Have known immunocompromised household contacts for example those with cancer, onimmunosuppressive therapy, HIV etc.

• A clinically significant abnormality on physical examination, including a systolicblood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, or a resting pulse >100 beats/min or <55 beats/min (<50 beats/min for conditioned athletes).

• Pregnant, nursing, or planning to become pregnant within 29 days of receipt of thestudy product.

• In the 4 weeks following challenge, volunteer will be living with or having dailycontact with elderly persons aged 70 years or more, diapered individuals, personswith disabilities, children <2 years old, a woman known to be pregnant or nursing,or anyone with diminished immunity. This includes contact at work, home, school,day-care, nursing homes, or similar places.

• Work in a health care setting, day care center, or as a food handler in the 4 weeksfollowing the challenge with S. sonnei.

• Use of any investigational drug or any investigational vaccine within 60 dayspreceding challenge, or planned use during the 6 months after receipt of the studyagent.

• Have received a licensed, live vaccine within 28 days or a licensed inactivatedvaccine within 14 days of receiving the challenge inoculum.

• Inability to comply with inpatient rules and regulations.

• Has any other condition that, in the opinion of the Investigator, would jeopardizethe safety or rights of a volunteer (e.g., infection with another detected pathogen)or would render the volunteer unable to comply with the protocol.

• Received blood or blood products within the past six months.