Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

E.W. "Al" Thrasher

Status: Funded - Closed

Newborn vitamin A supplements, gut microbiota and vaccine response at 15-18m in Bangladeshi infants

Charles Stephensen, PhD

Summary

BACKGROUND: Vitamin A deficiency impairs systemic and intestinal immune function mediated by T cells, and may thereby impair responses to standard vaccines given during infancy. In addition, impaired intestinal immunity early in infancy may also alter colonization of the infant intestine with beneficial bacteria such as Bifidobacterium longum, thus altering the bacterial ecology of the intestine and impairing normal growth and development. GAP: While vitamin A supplementation at 6 m of age is known to improve vitamin A status and decrease infant mortality in communities where vitamin A deficiency is common, the effects of vitamin A supplementation at birth have not been extensively examined. Since all infants are born with low vitamin A stores, early infancy is a vulnerable period and provision of supplements may improve immune function and affect establishment of a healthy intestinal microbiota. HYPOTHESIS: We will test the hypotheses that vitamin A supplementation at birth will (1) improve production of new T cells at 2 y of age; (2) improve T-cell memory responses to vaccines given early in infancy; and (3) alter intestinal colonization early in infancy at 2 y 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 vaccination. METHODS: We will recruit up to 304 infants at 2 y of age who participated in a randomized, double-blind, placebo-controlled intervention trial providing 50,000 IU vitamin A or placebo within 48 h of birth. Immunologic endpoints will be evaluated at 2 y of age, including responses to the oral polio virus vaccine, BCG vaccine, tetanus toxoid vaccine and hepatitis B virus vaccine. Intestinal microbiota will be evaluated by 16S rRNA gene sequencing early in infancy (6-15 w of age) and at 2 y of age. RESULTS: Pending. IMPACT: This study will determine if vitamin A supplementation at birth improves health by promoting colonization with health-promoting bacteria and improving vaccine responses.

Keywords:

Human, Immunity, Microbiome, Prospective Cohort, Treatment, Vaccine, Vitamin A

Publications: