Mapping the exposome of Zimbabwean preschool-aged children using a novel peptide microarray approach

Immune responses vary substantially between individuals and populations, reflecting differences in genetics, environment, and cumulative antigenic exposures. Characterizing these exposures, or the immunological exposome, is essential for understanding population-specific immune development, susceptibility to infection, and responses to interventions. Here, we present a proof-of-concept study applying a bespoke high-density peptide microarray to map the exposome of Zimbabwean preschool-aged children (PSAC). Using serum samples from 20 children under five years of age living in a schistosomiasis-endemic area, we profiled IgM and IgG responses against 5,614 peptides representing 280 pathogens, vaccines, allergens, and autoantigens. As internal validation, we used childhood vaccine antigens which the clinical records indicated the children had received. The platform successfully detected antibody responses to all the childhood vaccine antigens represented on the array, demonstrating sensitivities ranging from 87.5-100% for IgM and 61.5-100% for IgG. Beyond vaccine-associated responses, children exhibited diverse and highly heterogeneous antibody profiles, with strong reactivity to enteroviruses, Streptococcus spp., S, pneumoniae, Clostridium perfringens, Clostridioides difficile, and the zoonotic pathogen Ehrlichia canis. Distinct IgM and IgG signatures revealed evidence of both recent and historical antigenic exposures, highlighting the breadth of immune stimulation experienced early in life. These findings demonstrate the feasibility of high-throughput serological exposome mapping in African children and provide the first detailed characterization of the childhood immunological exposome in this setting. This approach offers a powerful tool for investigating immune heterogeneity, informing vaccine development, and establishing population-specific immune reference frameworks in high-burden environments.