Dose-Finding Study of Lyophilized Shigella Sonnei 53G Challenge Strain

Inclusion Criteria

• Male or non-pregnant female between 18 and 49 years of age (inclusive).
• General good health defined as (a) no significant medical illness, (b) no clinically significant physical examination findings and (c) no screening laboratory values significantly outside the normal limits of the testing laboratory within 45 days of challenge.
• Demonstrate comprehension of the protocol procedures and knowledge of study by passing a written examination (pass grade ≥70%) on day -1.
• Willing to sign an informed consent form (ICF).
• Willingness to participate for an inpatient stay lasting up to 11 days and an outpatient follow-up lasting 6 months from challenge.
• Willing to not smoke during the inpatient stay.
• Available for all planned follow-up visits.
• Negative serum pregnancy test at screening and negative urine pregnancy test on the day of admission to the inpatient phase for female subjects of childbearing potential. Females of childbearing potential must agree to use an effective method of birth control (birth control pills, injection hormonal contraceptive, implant hormonal contraceptive,

hormonal patch, intrauterine device (IUD), sterilization by hysterectomy or tubal ligation, spermicidal products and barrier methods such as cervical sponge, diaphragm, or condom) within two months of challenge and during the entire study. Abstinence is acceptable. A woman is eligible if she is monogamous with a vasectomized partner.

• Willing to not donate blood for up to 6 months after completion of the inpatient phase of the study.
• Willing to refrain from participation in another investigational vaccine or drug trial at least until after completion of the 6 month follow-up safety call.

Exclusion Criteria

• Presence of a significant medical condition (e.g. psychiatric conditions, alcohol or 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 opinion of the investigator precludes participation in the study.
• Immunosuppressive illness or immunoglobulin A (IgA) deficiency
• Positive serology results for HIV, HBsAg, hepatitis C virus (HCV), or syphilis (RPR) antibodies.
• Evidence of inflammatory arthritis on exam and/or human leukocyte antigen B27 (HLA-B27) positive.
• Family history of inflammatory arthritis.
• Significant abnormalities in screening lab hematology or serum chemistry, as determined by PI.
• Allergy to fluoroquinolones or trimethoprim-sulfamethoxazole
• Fewer than 3 stools per week or more than 3 stools per day as the usual frequency.
• History of diarrhea 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 over the counter (OTC) medications that contain Imodium, acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs, during the 48 hours prior to investigational product administration
• Travel within two years prior to dosing to countries where Shigella infection is endemic.
• Use of any medication known to affect the immune function [e.g., oral steroids, parenteral steroids, or high-dose inhaled steroids (>800 μg/day of beclomethasone dipropionate or equivalent and others): nasal and topical steroids are allowed] within 30 days preceding receipt of the challenge inoculum or planned use during the active study period.
• Serologic evidence of Shigella sonnei (titer > 1:2500)
• A positive urine test for opiates.
• A chronic disease (such as hypertension, hyperlipidemia or anxiety/depression) for which doses of prescription medications are not stable for at least the past 3 months.
• Scheduled and/or long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (>800 μg/day of beclomethasone dipropionate or equivalent) within the