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Safety, Immunogenicity and Efficacy of Shigella Conjugate Vaccines in 1-4 Year Olds in Israel

NCT00368316 · Status: COMPLETED · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 2799

Last updated 2012-06-22

Study results available
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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.

Conditions

  • Shigellosis

Interventions

BIOLOGICAL

Shigella conjugate vaccines

Shigella sonnei-rEPA and Shigella flexneri2a rEPA vaccines

Sponsors & Collaborators

  • The Chaim Sheba Medical Center

    collaborator OTHER

  • Schneider Children's Medical Center, Israel

    collaborator OTHER

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    lead NIH

Principal Investigators

  • Rachel Schneerson, MD · PDMI, NICHD, NIH

Study Design

Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Model
PARALLEL

Eligibility

Min Age
1 Year
Max Age
4 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2003-01-31
Primary Completion
2008-01-31
Completion
2009-02-28

Countries

  • Israel

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00368316 on ClinicalTrials.gov