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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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
Infant specimens containing DNA isolated from periferal blood mononuclear cells (PBMC) will be retained for future analyses. Maternal specimens containing DNA from cheek swabs will be retained for future analyses.
|Study Start Date:||October 2014|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02027610
|Contact: Shaikh M. Ahmad, PhD||(+88 02) 9827001-10|
|Contact: Charles B Stephensen, PhD||530-754-9266||Charles.Stephensen@ars.usda.gov|
|United States, California|
|University of California, Davis||Active, not recruiting|
|Davis, California, United States, 95616|
|USDA Western Human Nutrition Research Center||Active, not recru