Safety Study of Inactivated Shigella Whole Cell Vaccine in Adults
Condition: Shigellosis
MeSH terms: Dysentery, Bacillary
Intervention: Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 dose; Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 doses; Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 doses; Vaccine: 2.6±0.8 x 10^11 vp/mL, 3 doses; Placebo: 1-3 doses
Intervention description: Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^8 vp/mL administered on Day 0; Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^9 vp/mL administered on Days 0, 28, and 56; Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^10 vp/mL administered on Days 0, 28, and 56; Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^11 vp/mL administered on Days 0, 28, and 56; Placebo administered on Day 0 (if 1 dose) or Day 0, 28, and 56 (3 doses)
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 82.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Shigella; vaccine; shigellosis; dysentery; whole cell

Summary:

      This is a research study about an experimental (investigational) oral inactivated whole cell
      Shigella flexneri 2a killed vaccine (Sf2aWC). Sf2aWC is a killed vaccine that is being made
      to prevent disease from Shigella., which causes bloody, watery diarrhea. Infants and children
      living in developing countries experience the greatest consequences of this disease. The
      purpose of this study is to find a dose of the vaccine that is safe, tolerable, and develops
      an immune response. About 82 healthy adults, ages 18-45, will participate in this study. This
      study will require volunteers to stay in the research facility for several nights for the
      first dose. Participants in Cohorts 2, 3, and 4 will not be required to stay overnight for
      the second and third doses. Participants will be assigned to receive 1 of 4 vaccine doses by
      mouth. Study procedures include: stool samples, blood samples and documenting side effects.
      Participants will be involved in study related procedures for about 8 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy adults, male or female, age 18 to 45 years (inclusive) at the time of
             enrollment.

          -  Completion and review of comprehension test (achieved >70% accuracy).

          -  Signed informed consent form.

          -  Available for the required follow-up period and scheduled clinic visits.

          -  Negative urine pregnancy test before each vaccination for female subjects of
             childbearing potential. Females of childbearing potential must agree to use an
             efficacious hormonal or barrier method of birth control during the study. Abstinence
             is also acceptable.

        Exclusion Criteria:

          -  Presence of a significant medical or psychiatric condition that in the opinion of the
             investigator precludes participation in the study. Some medical conditions, that are
             adequately treated and stable, would not preclude entry into the study. These
             conditions might include stable asthma, hypertension or depression controlled with
             medication.

          -  Clinically significant abnormalities on physical examination.

          -  Clinically significant abnormalities in screening hematology, serum chemistry, or
             urinalysis as determined by PI or PI in consultation with Medical Monitor.

          -  History of febrile illness within 48 hours prior to vaccination.

          -  BMI <19 or >34.

          -  Positive blood test for HBsAG, hepatitis C virus (HCV), HIV-1, Human leukocyte antigen
             (HLA)-B27.

          -  Women currently nursing.

          -  History of reactive arthritis.

          -  Evidence of current excessive alcohol consumption

          -  Evidence of current drug use or drug dependence.

          -  Regular use of anti-diarrheal, anti-constipation, or antacid therapy (excluding use
             associated with spicy meals).

          -  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.

          -  Personal or family history of an inflammatory arthritis.

          -  History of allergy to soy products.

          -  History of microbiologically confirmed Shigella infection within 3 years.

          -  Prior receipt of experimental Shigella vaccine or live Shigella challenge within 3
             years.

          -  Symptoms of travelers' diarrhea associated with travel to countries where Shigella or
             other enteric infections are endemic (most of the developing world) within 1 year
             prior to dosing.

          -  Occupation involving handling of Shigella bacteria currently, or in the past 3 years.

          -  History of diarrhea during the 7 days before vaccination.

          -  Use of antibiotics during the 7 days before vaccination.

          -  Use of proton pump inhibitors, H2 blockers, or antacids within 48 hours prior to
             dosing.

          -  Inability to comply with inpatient rules and regulations.

          -  Use of immunosuppressive and/or immunomodulative drugs such as corticosteroids or
             chemotherapeutics that may influence antibody development.

          -  Participation in research involving another investigational product (defined as
             receipt of investigational product or exposure to invasive investigational device) 30
             days before planned date of first vaccination.