Does the Fecal Microbiome Influence Rotarix Immunogenicity

Study Overview
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Brief Summary
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This is a proposal for a nested case-control study within an ongoing rotavirus vaccine immunogenicity clinical trial 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 Infections, Reaction - Vaccine Nos, Intestinal Bacteria Flora Disturbance

Participation Criteria
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Eligibility Criteria
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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 into in the study. Written informed consent obtained from the parents or guardians. Availability of baseline fecal sample collected before Rotarix vaccination Written informed consent obtained from the parents or guardians for nested study 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 trial (besides NCT01199874). Birth weight less than 1500 grams; or if birth weight 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 Immunoglobulin A (> 20 U/ml) at 6 weeks of age, indicative of prior rotavirus infection

Ages Eligible for Study
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Minimum Age: 4 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case: non-rotavirus seroconverters<br>Infants not demonstrating seroconversion to rotavirus vaccination, as measured anti-RV Immunoglobulin A < 20 U/ml | |
| Control: rotavirus seroconverters<br>Infants demonstrating seroconversion to rotavirus vaccination, as measured by anti-rotavirus Immunoglobulin A > 20 U/ml | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| microbiome diversity (Shannon's index) and composition (relative abundance) | Microbiota composition will be measured by calculating and comparing a % of the phylogenetic groups present in both groups Diversity will be measured by calculating a comparing a Shannon's reciprocal index of diversity, 1/D in both groups The relative abundance of microbial groups will be measured by calculating and comparing the ribosomal ribonucleic acid gene copy per gram of feces over time in both groups | at 6 weeks of age, pre-rotavirus vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| microbiome diversity (Shannon's index) and composition (relative abundance) | Microbiota composition post vaccination will be measured by calculating and comparing a % of the phylogenetic groups present in both groups Diversity post vaccination will be measured by calculating a comparing a Shannon's reciprocal index of diversity, 1/D in both groups The relative abundance of microbial groups post vaccination will be measured by calculating and comparing the ribosomal ribonucleic acid gene copy per gram of feces over time in both groups | at 1 to 3 years of age post-rotavirus vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rotavirus, immunogenicity, enteric vaccine, vaccine immunogenicity, rotavirus vaccine, gut microbiome, microbiome