Safety Study of Inactivated Shigella Whole Cell Vaccine in Adults
Condition: Shigellosis
MeSH terms: Dysentery, Bacillary
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      Despite the public health burden of Shigella spp. on travelers, deployed soldiers and, most
      significantly, young children in the developing world, there is no licensed vaccine against
      Shigella. The rationale for using Shigella flexneri 2a whole cell killed vaccine (Sf2aWC), is
      that it is expected to be especially well tolerated by subjects. If Sf2aWC is safe and
      immunogenic, it may be combined with S. sonnei and S. flexneri 3a as the basis of a
      multivalent vaccine, because these three components should cover up to 80% of shigella
      infections in developing countries and over 90% in developed countries. This is a single
      site, Phase 1, double-blind, randomized, placebo-controlled, dose-escalation study in healthy
      adult subjects. Approximately 82 subjects will be enrolled into four separate cohorts and
      will be randomized to receive Sf2aWC or placebo. The placebo preparation will be bicarbonate
      buffer. Cohort 1 subjects will receive a single oral dose of Sf2aWC (2.6±0.8 x 10^8 vp/mL) or
      placebo. Dosing and 72 hours of supervised post-vaccination safety follow-up will be
      conducted in the Center for Immunization Research, Johns Hopkins School of Public Health
      (CIR) Inpatient Unit. Before enrolling subjects in subsequent cohorts, safety data from the
      previous Cohort(s) through Study Day 7 will be evaluated and reviewed by the Safety Review
      Committee (SRC). Cohorts 2, 3, and 4 participants will receive three doses of Sf2aWC vaccine
      or placebo at 0, 1 and 2 months. The first immunization will be administered in the CIR
      inpatient unit, followed by 72 hours of direct post-immunization observation. If after review
      by the SRC the first dose appears safe and well tolerated, subsequent doses will be
      administered on an outpatient basis. Safety will be assessed by solicited symptoms/subject
      memory aid and laboratory evaluations. Adverse events (AE)s will be graded according to
      standardized criteria. The immunogenicity outcome measures of interest include serum
      immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies by ELISA against S. flexneri 2a
      Lipopolysaccharide (LPS) and S. flexneri 2a invasive protein antigens (Ipa), cytokine assays,
      B and T cell memory responses, and vaccine-specific IgA responses. The proposed sample size
      of twenty per group in Cohorts 2, 3, and 4 would be sufficient to select the appropriate dose
      to move into the next study phase, providing that a difference in the immunogenicity between
      the two arms is 20% or greater. Participants will include 82 healthy adult male and female
      subjects, ages 18 to 45 inclusive. The primary objective of this study is to assess the
      safety and tolerability of Sf2aWC vaccine when administered in three oral doses over a range
      of dose levels in healthy adult subjects. The secondary objective is to assess the
      immunogenicity of the Sf2aWC vaccine over a range of doses in healthy adult subjects.
    

Intervention name(s): 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 type(s): Biological; Biological; Biological; Biological; Biological
Intervention description(s): 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Shigella; vaccine; shigellosis; dysentery; whole cell