Location: Immunity and Disease Prevention Research
Project Number: 2032-53000-001-12-A
Project Type: Cooperative Agreement
Start Date: Mar 1, 2014
End Date: Dec 31, 2016
The objective of this agreement is to conduct a research study entitled “Newborn vitamin A supplements, gut microbiota, and vaccine response at 15-18 m in Bangladeshi infants” that is funded by the Thrasher Research Fund. The study is being conducted in Dhaka, Bangladesh. In this study we will test the hypotheses that vitamin A supplementation (VAS) at birth will: (1) improve production of new T cells at 15-18 m of age; (2) improve T-cell memory responses at 15-18 m of age to vaccines given early in infancy (birth–14 wk); and (3) alter intestinal colonization early in infancy (6, 11, and 15 wk) and at 15-18 m of age to increase Bifidobacterium and other healthy bacteria and decrease Proteobacteria and other harmful bacteria. Furthermore these differences in composition of the intestinal bacteria will be associated with greater immunologic responses to oral and systemic vaccines. Specific Aim 1: Determine if VAS or placebo at birth affect the blood concentration and thymic output of naïve T-cells at 15-18 m of age. Specific Aim 2: Determine if VAS or placebo at birth affect T-cell mediated responses at 15-18 m of age to vaccines given early in infancy, including serum and intestinal antibody levels, vaccine-specific proliferative responses by T cells and cytokine production by T cells. Specific Aim 3: Determine if VAS or placebo at birth affect the relative abundance of healthy intestinal bacteria and common harmful bacteria in the feces at 6, 11, and 15 wk of age and at 15-18 m of age and determine if relative abundance of these bacteria correlates with vaccine responses shortly after vaccination (6, 11, 15 wk) and later in infancy (15-18 m).
This study involves follow-up of infants that participated in an earlier trial (ARS Agreement #59-5306-1-081F). This study will recruit up to 300 infants from that previous study that gave high-dose VAS or placebo at birth to infants in Dhaka, Bangladesh. Vaccines were given at birth, 6, 10, and 14 wk of age, blood collected at 6 and 15 wk and stool at 6, 11, and 15 wk. Infants will be enrolled in the present trial at 15-18 m of age to collect blood for evaluation of vaccine responses and stool for assessment of the gut microbiome. The sample size of the ongoing study was based on the expected effect on vaccine response and this estimate should be appropriate for the present study.