Tuesday, March 18, 2025
3/18/2025
ABSTRACT Understanding microbial shifts and how they affect vaccine response is central to this study. We will determine if gut microbial communities associated with breastfeeding in the HEU infant follows the same successional trajectory as HU controls and resolve the differences at functional level. How the continuous conditioning of the infant gut by the microbiota from the breast milk affects the infant microbiome and subsequent immune responses to pediatric vaccination is not known and would also be studied in this submission. Teasing out possible humoral vaccine differences due to HLA associations will be an important component to consider when identifying the mechanism and impact of microbial ecological conditioning through the breast milk towards vaccine responsiveness. Our submission proposes to use biological samples collected at regular intervals over a 12-month period from a multi-site study of well characterized cohort of mother: infant pairs of HEU and HU controls from Nigeria and South Africa to investigate both host and microbial genetic determinants of altered immunity in African infants. However, the COVID-19 pandemic that hit in 2021 however disrupted our work for about 18 months since the laboratories were closed under lockdown in addition to challenges due to hike in cost of laboratory consumables and reagents, delay and cancellation of shipments, and loss of man hours due to ill health of staff and family members due to COVID-19. Our administrative supplemental submission is to request for an extension from 1 July 2023 to 30 June 2023 to continue to investigate microbial shifts and how they affect growth and immune response to pediatric vaccines in HEU infants as compared to matched HU controls. Our hypothesis is that breast milk microbiota conditioning in newborn infants impacts growth and immune responsiveness to pediatric vaccines in the context of inherited HLA variants. We will continue to test our hypothesis through the same specific aims: Aim 1: Compare the ontogeny of microbial structure and metabolome in longitudinal breast milk and stool samples of corresponding 200 Exclusively Breast Fed (EBF) HEU versus 100 EBF HU control, infants over the first 12 months of life to document influence of the milk microbiota on the infant gut microbiome; and their collective effect or association with growth. Aim 2: Assess the relationship between infant microbial structure and humoral immune responses to pediatric vaccines AIM 3: To associate inherited HLA gene variants with humoral immune responses to pediatric vaccines in the two infant groups. This proposal will interrogate both host and microbial genetic determinants of altered immunity in HEU and is therefore highly relevant and responsive to the original RFA RM16-013.
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