Vitamin A, Stool Microbiota and Vaccine Response in Bangladeshi Infants
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|ClinicalTrials.gov Identifier: NCT02027610|
Recruitment Status : Completed
First Posted : January 6, 2014
Last Update Posted : November 18, 2015
|Condition or disease|
|Vitamin A Deficiency|
Hypotheses and Specific Aims The investigators will test the hypotheses that VAS at birth will (1) improve production of new T cells at 1-2 yr of age; (2) improve T-cell memory responses at 1-2 yr 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 1-2 yr of age to increase Bifidobacterium and other healthy bacteria and decrease Proteobacteria and other harmful bacteria. Because the "secretor status" of the mother affects the carbohydrate content of the breastmilk, which can in turn affect Bifidobacterium growth in the infant gut, the "secretor status" of the mother will be determined. 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 1-2 yr of age. Specific Aim 2: Determine if VAS or placebo at birth affect T-cell mediated responses at 1-2 yr 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 1-2 yr 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 (1-2 yr). As part of Aim 3 the "secretor status" genotype (FUT2 gene) of the mother will be determined from a cheek swab DNA sample.
|Study Type :||Observational|
|Actual Enrollment :||258 participants|
|Official Title:||Newborn Vitamin A Supplementation, Gut Microbiota and Vaccine Response During the Second Year of Life in Bangladeshi Infants|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||September 2015|
|Actual Study Completion Date :||September 2015|
- Naïve T-cells in peripheral blood [ Time Frame: measured once at 52 - 104 weeks of age ]The concentration of naïve T-cells in peripheral blood will be measured once at 52 - 104 wk of age by flow cytometric analysis.
- Thymic output of naïve T cells [ Time Frame: measured once at 52 - 104 weeks of age ]The thymic output of naïve T cells will be measured once at 52 - 104 wk of age by T-cell receptor excision circle (TREC) levels in DNA purified from peripheral blood mononuclear cells (PBMC).
- Immune response to vaccines [ Time Frame: Measured once at 52 - 104 weeks of age ]The immune responses to vaccines, measured at 52 - 104 wk of age, include: (A) Serum immunoglobulin G (IgG) and immunoglobulin A (IgA) responses to oral polio virus vaccine (OPV; given at birth, 6 wk, 10 wk, 14 wk); (B) serum IgG response to tetanus toxoid vaccine (TT; given at 6, 10 and 14 wk) and (C) Hepatitis B virus vaccine (HBV; given at 6, 10 and 14 wk); (D) the IgA response to OPV in stool; the (E) proliferative and (F) cytokine response of peripheral blood cluster of differentiation 4 (CD4) T-cells to OPV, TT, HBV vaccines and to the tuberculosis vaccine (BCG; given at birth). Antibody responses will be measured by ELISA, T-cell proliferation by flow cytometric analysis after 6 days of culture with corresponding vaccine antigens, and cytokines will be measured in supernatant after 3 and 6 d of culture with the same antigens.
- Change in the relative abundance of stool bacteria [ Time Frame: 6, 10, 14 and 52-104 weeks of age ]The relative abundance of stool bacteria will be measured using DNA extracts at four time points (6, 10 and 14 wk, and at one point between 52 and 104 wk) using culture-independent, next generation sequencing (NGS) of bacterial populations, followed by quantitative PCR (QPCR) and Bifidobacterium-specific terminal restriction-fragment-length polymorphism (TRFLP.)
- Serum Vitamin A status [ Time Frame: measured once at 52-104 weeks of age ]Vitamin A status will be assessed by serum retinol or retinol binding protein (RBP4) at 52 - 104 wk of age.
- Secretor status of the study infant's mother. [ Time Frame: measured once when infant is 52 - 104 weeks of age ]The "secretor status" of the mother is determined by the FUT2 genotype. FUT2 is related to FUT1, the gene encoding fucosyltransferase 1, which determines the composition of specific glycans on erythrocytes that determine the ABO (or ABH) and Lewis blood group antigens. The activity of fucosyltransferase 2 (encoded by FUT2) causes the synthesis and secretion of these same glycans into breast milk and other secretions (e.g., saliva and other intestinal secretions).
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02027610
|United States, California|
|University of California, Davis|
|Davis, California, United States, 95616|
|USDA Western Human Nutrition Research Center|
|Davis, California, United States, 95616|
|International Centre for Diarrhoeal Disease Research, Bangladesh|
|Dhaka, Bangladesh, 1212|
|Principal Investigator:||Charles B Stephensen, PhD||USDA, Western Human Nutrition Research Center|