Exploration of the Biologic Basis for Underperformance of Oral Polio and Rotavirus Vaccines in Bangladesh

Oral polio and rotavirus vaccines are significantly less effective in children living in the developing world. Environmental 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 objective of the study was to determine the association of environmental enteropathy with the efficacy of oral polio and rotavirus vaccines in children in Bangladesh. Secondary and exploratory objectives were designed to address other possible causes of oral vaccine underperformance including malnutrition, interference with maternal or breastmilk antibodies, changes in gut microbiota, and genetic susceptibility. The PROVIDE (Performance of Rotavirus and Oral Polio Vaccines in Developing Countries) study was structured as a 2x2 clinical trial with a prospective birth cohort enrollment of 700 infants and their mothers in the urban slum of Mirpur, Dhaka, Bangladesh. All children received the full series of Bangladesh's Expanded Program on Immunization vaccines, including oral polio vaccine (OPV) and followed for their first 2 years of life. Half the children were randomized to receive an inactivated polio vaccine (IPV) for their 4th dose at 39 weeks instead of the standard OPV dose. In the other trial, half the infants received the 2-dose rotavirus vaccine (Rotarix) with delayed dosing at 10 and 17 weeks of age. A detailed description of the study design and procedures can be obtained from PROVIDE methods publication: Kirkpatrick B.D., Colgate R.E., Mychaleckyj J.C., Haque R., Dorothy D.M., Carmolli M.P., et al., 2015, PMID: 25711607 The Poliovirus trial and results are described in Mychaleckyj et al, 2016, PMID: 26643930 The Rotavirus trial and results are described in Colgate et al., 2016, PMID: 27217217 The PROVIDE infants were genotyped on a custom Affymetrix Axiom array (30K SNPs) at the University of Virginia Center for Public Health Genomics; and on a pre-production version of the Illumina MEGA v2 chip at the Wellcome Trust Sanger Institute, UK. The latter genotyping was performed under the auspices of the VaccGene Consortium. Molecular data on a sub-set of subjects (22) was funded by R21 AI103536 (to C.G.). Analyses are ongoing to identify variants associated with the included phenotypes. The genotyping methods and analysis are described in PMID: 29514873.]]>
Inclusion Criteria:All of the following criteria must be met for a subject to be eligible to participate in the study: Mother willing to sign informed consent form. Healthy infant aged 0 to 7 days old. No obvious congenital abnormalities or birth defects. No abnormal (frequency and consistency) stools since birth. Stable household with no plans to leave the area for the next one year. Exclusion Criteria: Meeting any of the following criteria at baseline will exclude a subject from study participation: Parents are not willing to have child vaccinated at the ICDDR, B field clinic. Parents are not willing to have child's blood drawn. Parents are planning to enroll child into another interventional clinical study during the time period of this trial that could affect the outcomes of this study. Mother not willing to have blood drawn and breast milk extracted. Parents not willing to have field research assistant in home two times per week. History of seizures or other apparent neurologic disorders. Infant received any vaccines before start of study, except BCG. Infant has any sibling currently or previously enrolled in this study, including a twin. ]]>
Enrollment for the PROVIDE study occurred between May 2011 and November 2012. The infants were followed by twice-weekly household visits and scheduled clinic visits over the first 2 years of life.]]>