microbiota measured early in infancy and during the second year of life, and explore the association of the gut microbiota with vaccine response. Mothers of study infants will participate in the study because the breast milk oligosaccharide content strongly affects gut microbiota composition and the "secretor status" of the mother, which can be determined from maternal FUT2 genotype, strongly affects breast milk oligosaccharide content.
Vitamin A Deficiency
|Study Design:||Observational Model: Cohort
Time Perspective: Cross-Sectional
|Official Title:||Newborn Vitamin A Supplementation, Gut Microbiota and Vaccine Response During the Second Year of Life in Bangladeshi Infants|
- Naïve T-cells in peripheral blood [ Time Frame: measured once at 52 - 104 weeks of age ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ 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 wil