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Exploration of the biologic basis for underperformance of oral polio and rotavirus vaccines. Progress to Date - Bangladesh. Oral polio and rotavirus vaccines are significantly less effective in children living in the developing world compared to peers in other countries.
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Progress to Date - Bangladesh
Oral polio and rotavirus vaccines are significantly less effective in children
living in the developing world compared to peers in other countries.
Tropical enteropathy, which is associated with intestinal inflammation,
decreased absorption and increased permeability, may contribute substantially
to oral vaccine failure in developing country settings. The primary hypothesis
of this clinical trial is that tropical enteropathy decreases the effectiveness
of oral polio and rotavirus vaccines in infants by disrupting the enteric
This single-blind study will enroll 1,070 healthy infants and their mothers
residing in urban slums in Dhaka, Bangladesh and Kolkata, India in two
prospective cohorts. The Bangladesh arm of the study, enrolling 700 infants from May 2011, will employ a 2x2 factorial study design, separately randomizing infants to receive oral rotavirus vaccine (Rotarix) and a boost of inactivated polio vaccine (IPV). The India arm of the study, enrolling 370 infants from early 2012, will randomize infants for a boost of IPV.
The trial will investigate other possible causes of oral vaccine underperformance,
including: malnutrition, interference with maternal or breast milk antibodies,
changes in gut microbiota, and genetic susceptibility.
2 x 2 Factorial Study Design (Bangladesh)
Group A Rotarix + No IPV (175)
Group B Rotarix + with IPV boost (175)
Group C No Rotarix + No IPV (175)
Group D No Rotarix + with IPV boost (175)
This research is funded through the generous support of Bill and Melinda Gates Foundation.
Determine whether decreased vaccine responsiveness to oral polio or rotavirus vaccines is associated with the presence of
Determine the impact of an inactivated polio vaccine (IPV) boost on systemic (neutralizing antibodies) and mucosal immune
responses (shedding OPV vaccine virus) to polio vaccines following vaccination with oral polio vaccine (OPV).
Determine the efficacy of rotavirus vaccination to prevent rotavirus diarrhea.
Describe the impact on vaccine failure and tropical enteropathy due to:
Devise novel cellular assays to explore immunologic phenotypes with vaccine failure and TE (Mark Davis, Stanford)
Evaluate modified immunogenicity assays and biomarkers
Conducted extractions for fecal IgAanalysis on:
Week 6 specimens 130
Week 17 specimens 19
Week 18 specimens 9
Shipped 252 stool specimens to the Bangladesh National Polio Lab for vaccine excretion analysis. Received preliminary results on 66 specimens.
Processed 156 Week 6 blood specimens and 35 Week 18 blood specimens.
Shipped 130 whole blood specimens to Children’s Hospital Oakland Research Institute for HLA analysis.
Completed initial processing of 150 whole blood specimens for Phosphoflow analysis and shipped to Stanford University.
Completed piloting of ALS assay for both rotavirus and polio.
Colgate ER, Kirkpatrick BD (University of Vermont); Haque R, Qadri F, Zaman K (ICDDR,B); Sur D (NICED); Czerkinsky C (IVI);
Davis M (Stanford University); Gordon J (Washington University); Mychaleckyj J, Petri WA (University of Virginia)
Clinical Progress since May 2011
Households surveilled 28,000+
Infants Screened 363
Infants Enrolled 215 (59% of screened)
Adverse Events 16
Serious Adverse Events 6
Early Withdrawals 33 (15% of enrolled)
Protocol Deviations 204
Infant blood 2ml – 5ml
Vaccine shedding stools
Study visit stools
Mother breast milk
Gestational age assessment
Anthropometry: child and mother
Biweekly diarrhea surveillance
Oral Polio Vaccine Efficacy2
Rotavirus Vaccine Efficacy1
Malnourished children (by HAZ) in Dhaka are more unresponsive to OPV.
1Parashar UD, Glass RI. Rotavirus vaccines--early success, remaining questions. N Engl J Med. Mar 12 2009;360(11):1063-1065.
2Petri, Snider, Pallansch, and Haque (unpublished)