The Influence of the Microbiome on Rotavirus Vaccine Immunogenic Response in Infants in Karachi, Pakistan

Study Overview
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Brief Summary
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This is a nested case-control study within an ongoing rotavirus vaccine immunogenicity trial in Karachi, Pakistan. The primary study aim is to compare the fecal microbiota composition and diversity of infants who do (control) and do not (case) demonstrate immune seroconversion to rotavirus vaccination. The infants will be matched for vaccination dose, age and breast-feeding practices.

Official Title
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Nested Case-control Analysis of the Influence of the Microbiome on Rotavirus Vaccine Immunogenic Response in Infants in Karachi, Pakistan

Conditions
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Rotavirus

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants already consented and enrolled in the overarching study: Immunogenicity of Rotavirus Vaccine Under Different Age Schedules and the Impact of Withholding Breast Feeding around the Time of Vaccination on the Immunogenicity or Rotarix Vaccine trial (NCT01199874) Overarching study (NCT01199874)inclusion criteria: 6 weeks 0 days to 7 weeks 6 days age at the time of enrollment Healthy infant free of chronic or serious medical condition as determined by history and physical exam at time of enrollment written informed consent obtained from parents or guardians for overarching study Nested study additional inclusion criteria written informed consent obtained from parents or legal guardians for this nested study availability of a baseline, pre-vaccination fecal sample Exclusion Criteria: Overarching study (NCT01199874)exclusion criteria hypersensitivity to any of the vaccine components Use of any investigational drug or vaccine other than the study vaccine within 30 days of first dose of study vaccine or during the study use of any immunosuppressive drugs previous intussusceptions or abdominal surgery enrollment in any other trials birth weight less than 1500 grams; or if birthweight is unknown, weight less than 2000 grams on or before 28 days immunoglobulin and/or blood products use since birth or during the study period Nested study additional exclusion criteria positive serum anti-rotavirus IgA (> or= 20U/mL) at 6 weeks of age, indicative of rotavirus infection prior to vaccination

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| rotavirus (Rotarix TM) vaccination<br>Infants who received rotavirus vaccination (Rotarix TM) at 6 and 10 weeks, 10 and 14 weeks or 6,10, and 14 weeks. This is a nested study and infants received the vaccination in the overarching study: The Immunogenicity of ROtavirus Vaccine Under Different Age Schedules and the Impact of Withholding Breast Feeding around the Time of Vaccination on the Immunogenicity of Rotarix Vaccine (clinicaltrials.gov: NCT01199874) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| differences in fecal microbiota composition | The primary study objective is to see if there are significant differences in the fecal microbiota composition between rotavirus vaccine (Rotarix TM) immune responders (defined as anti-RV IgA antibodies at a concentration of > or = to 20 U/ml in a previously seronegative individual 4 weeks after the last Rotarix dose) and rotavirus vaccine immune non-responders (defined as anti-RV IgA antibodies at a concentration of <20 U/mL 4 weeks after the last Rotarix dose) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rotavirus vaccine, human microbiome, fecal microbiome, vaccine immunogenicity, Rotarix, immune response, mucosal