Safety, Immunogenicity and Efficacy of Shigella Conjugate Vaccines in 1-4 Year Olds in Israel
Condition: Shigellosis
MeSH terms: Dysentery, Bacillary
Intervention: Shigella conjugate vaccines
Intervention description: Shigella sonnei-rEPA and Shigella flexneri2a rEPA vaccines
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2799.0
Sex: All
Minimum age: 1 Year
Maximum age: 4 Years
Healthy volunteers: No
Keywords: Dysentery; S. sonnei; Antibody Response; Protection

Summary:

      Shigellosis remains a serious and frequent disease throughout the world. Development of
      vaccines has been difficult because shigellae are habitants of and pathogens for humans only
      and there is no consensus about the mechanism(s) of immunity to this pathogen.

      Incomplete, but compelling evidence, indicates that a critical level of serum IgG anti-LPS
      confers immunity to shigellosis. Important data come from our clinical trial in the Israel
      Defense Forces (IDF) recruits. A randomized, double-blind, vaccine-controlled study showed
      that the S. sonnei-rEPA elicited 74% protection against shigellosis occurring about 3 months
      after vaccination (p=0.001). This vaccine conferred 43% (p=0.04) protection in one company
      during an outbreak up to 14 days following vaccination suggesting that our Shigella
      conjugates might be of value in epidemics. The efficacy of S. sonnei-rEPA was correlated with
      the level of vaccine-induced IgG antibodies.

      The highest incidence, morbidity, and mortality of shigellosis is in young children. But
      serum antibody responsiveness to polysaccharide-based vaccines is age-dependent and infants
      and young children respond poorly or not at all to both disease and vaccination. The safety
      and immunogenicity of these Shigella conjugates in 4 to 6 years-old children in Israel was
      demonstrated. But although the fold rise in anti-LPS was similar in the children, the level
      of anti-LPS elicited by the conjugates was lower than in adults. We improved the
      immunogenicity of Shigella conjugates as shown in mice and then in adult humans. Now we apply
      to evaluate the safety, immunogenicity and efficacy of these improved conjugates in 1 to 4
      years-old children in Israel.

      In Israel, shigellosis is common especially in children. S. sonnei (Group D) comprise about
      60% of the isolates followed by S. flexneri (Group B): Shigella dysenteriae type 1 (Group A)
      is not found. We propose to administer 2 injections of either S. sonnei-CRM9 or S. flexneri
      type 2a-rEPAsucc 6 weeks apart in a random double-blind fashion to about 6,000 1 to 4
      year-olds. Active surveillance of the vaccinees for enteric infections will be maintained for
      at least 2 years to evaluate the effect of vaccination.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Volunteers who are healthy 1-4 year old children whose parents/guardians have read the
        Information Sheet provided by the Principal Investigator and signed the consent form, and
        who will be available for follow up.

        EXCLUSION CRITERIA: Children with

          -  chronic diseases receiving medication;

          -  who have received systemic steroids during the month preceding Shigella vaccination;

          -  who had severe side effects following vaccinations; and

          -  those not available for follow up.