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

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

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.

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