Trained immunity in BCG vaccinated African infants from Malawi (TIA) Study: M’mera Mpoyamba

TIA study also known as M’mera Mpoyamba aims to build a single-cell paediatric atlas of cord and peripheral myeloid and lymphoid cell development, following BCG vaccination in the first year of life. This atlas will increase representation of African people in the existing body of HCA (Human Cell Atlas) atlases and will be used as a healthy paediatric reference atlas for myeloid and lymphoid developmental cell lineages. This atlas will be instrumental for future functional studies that aim to determine mechanistic links between cell states and disease, much like the human genome project, but with high resolution in single cells. Our study will help delineate the development of myeloid and lymphoid immune cells in early life, following BCG vaccination in an African setting; and increase the diversity of the existing HCA reference maps.

Our secondary goal is to determine the epigenetic effects of BCG vaccination on infant immunological development and function. To do this we will measure histone modifications in open regions of chromatin (the DNA scaffold) that regulates the expression of DNA. Histones are a collection of proteins in the cell nucleus that help condense DNA into chromatin. Histones are post translationally modified (PTM) through various mechanisms including methylation, phosphorylation, acetylation, ubiquitylation, and sumoylation. PTM modifications play a fundamental role in gene expression by altering chromatin structure or recruiting histone modifiers, which impact many biological processes such as transcriptional activation/inactivation, DNA packaging and repair.

We will collect samples from 40 male and 40 female Malawian new-borns, across sex and time at Queen Elizabeth Central hospital labour ward. We will use next generation sequencing technology to measure RNA and histone modifications in these infants at high resolution at single cell level. For the greatest impact of our study, the deidentified data will be an open resource, on multiple levels, embedded within the existing HCA’s.

This study is the first of its kind and it will significantly advance the speed and scope of discovery research into human health and disease by providing a healthy genetically diverse reference atlas.