Phase 2b Challenge Study With the Bioconjugate Vaccine Flexyn2a
Condition: Shigellosis
MeSH terms: Dysentery, Bacillary
Intervention: Flexyn2a; Placebo
Intervention description: 2 doses of 10 μg of Flexyn2a will be injected intramuscularly 4 weeks apart; 2 doses of TBS solution will be injected intramuscularly 4 weeks apart
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      In this proof of concept challenge study, the bioconjugate candidate vaccine Flexyn2a will be
      tested for its ability to induce an immune response that protects healthy adult volunteers
      from infection with a wild-type Shigella flexneri 2a strain compared to subjects receiving
      placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female age 18-50 years (inclusive)

          -  Good health, without clinically significant medical history or physical examination
             findings.

          -  Negative serum pregnancy test at screening, and negative urine before each vaccination
             and before challenge for female subjects of childbearing potential.

          -  Females of childbearing potential must agree to avoid pregnancy by use of effective
             contraception. Abstinence is not acceptable as effective contraception. Female
             subjects unable to bear children must have this documented (e.g. tubal ligation or
             hysterectomy).

          -  Willingness to participate in the study after all aspects of the protocol have been
             explained and written informed consent obtained.

          -  Completion of a training session and demonstrated comprehension of the protocol
             procedures, knowledge of Shigella-associated illness, and a passing score of 70% or
             better on a written examination.

          -  Availability for the study duration, including all planned follow-up visits.

          -  Willingness to refrain from participating in other studies of investigational products
             until completion of the last study visit.

        Exclusion Criteria:

          -  Women currently nursing.

          -  Presence of a significant medical or psychiatric condition which in the opinion of the
             investigator precludes participation in the study.

          -  Clinically significant abnormalities in screening hematology or serum chemistry as
             determined by PI or PI in consultation with the research monitor and sponsor.

          -  Presence in the serum of HIV antibody, HBs-Ag, or HCV antibody (if confirmed positive
             by HepC confirmatory test, i.e. RIBA, PCR)

          -  Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).

          -  Evidence of current excessive alcohol consumption or drug dependence.

          -  Evidence of impaired immune function.

          -  BMI <19 and ≥35

          -  Recent vaccination or receipt of an investigational product (within 30 days before
             vaccination and until last study visit).

          -  Personal history of an inflammatory arthritis.

          -  Positive blood test for HLA-B27.

          -  Personal history of irritable bowel syndrome as defined by Rome III criteria.

          -  Treatment with immunoglobulins or blood products within 3 months from first candidate
             vaccine injection.

          -  Regularly abnormal stool pattern (fewer than 3 per week or more than 3 per day) or
             loose or liquid stools

          -  Regular use of laxatives, antacids, or other agents to lower stomach acidity.

          -  Use of any medication known to affect the immune function (e.g., systemic steroids)
             within 30 days preceding the first vaccination or planned use during the entire study
             period.

          -  Known allergy to any of the following antibiotics: ciprofloxacin,
             trimethoprim-sulfamethoxazole or penicillin.

          -  Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where
             Shigella infection is endemic (most of the developing world) within two years prior to
             dosing, OR planned travel to endemic countries during the length of the study.

          -  Vaccination for or ingestion of Shigella within 3 years prior to vaccination.

          -  Use of antibiotics during the 7 days before vaccination and challenge

          -  Use of proton pump inhibitors, H2 blockers or antacids within 48 hours prior to
             challenge.

          -  Serum IgG titer to Shigella flexneri 2a LPS ≥ 2500

          -  Current occupation involving handling of Shigella bacteria

          -  History of allergy to any vaccine or to soy

          -  Any other criteria which, in the investigator's opinion, would compromise the ability
             of the subject to participate in the study, the safety of the study, or the results of
             the study