Effects of improved water, sanitation, handwashing and nutrition on early childhood IgG immune repertoire development against Shigella and enteroinvasive Escherichia coli (EIEC)

We studied effects of a combined water, sanitation, handwashing, and nutritional supplementation (WSH+N) intervention on Shigella/ EIEC IgG immune development among Bangladeshi children enrolled in a cluster randomized trial. We used a bacterial display assay to measure IgG-specific binding to Shigella /EIEC Ipa proteins (IpaA, IpaB, IpaC, IpaD, IpaH) from a substudy of 120 children (60 intervention, 60 control) at median ages 3-, 14-, and 28-months. We found that the WSH+N intervention did not impact IgG seroprevalence (56% vs 53%, P=0.6) or IgG epitope repertoire development (P=0.15-0.97), but there were distinct age-based patterns of IgG linear epitopes and motifs charting the development of the immune repertoire. Samples from before age 6-months, reflecting predominantly maternal IgG, had higher epitope breadth and magnitude compared with samples from older ages. A modeling analysis of maternal-child IgG dynamics suggests peak susceptibility occurs between 6 and 9 months of age. With this methodology, we find that intensive, household-based WASH interventions were insufficient to reduce early childhood infection to Shigella /EIEC. Our results motivate complementary interventions, such as vaccines, to prevent Shigella /EIEC infection in the first two years of life.