Reconstructing pathogen-specific antibody binding epitopes and age-dependent immune signatures from proteomic-scale peptide libraries

Public health interventions involving improved water, sanitation and promotion of hygiene behaviors (WASH) plus nutrition, were implemented in Bangladesh in a large randomized controlled trial to assess impact on childhood enteric infection and diarrheal disease. Here, we evaluated magnitude and breadth of humoral responses to enteric pathogens in a subset of children among those received intervention (n=60) versus a control group (n=60) using an integrated method of bacterial display peptide library screening, next-generation sequencing and computational analysis to characterize individual antibody repertoires in serum collected at median ages of 3, 14 and 28 months. We determined high seroprevalence for enteric infections and show that antibody recognition of the putative epitopes and antigenic regions remained consistent over time. With mathematical models, we inferred waning of maternal immunity, and a subsequent immunity boost due to infection. Random peptide library screening has potential utility for rigorous analysis of antibody responses and identification of epitopes indicative of protective humoral immune responses.