Exploring the spectrum of human encounters with bacterial pathogens by profiling pathogen-specific antibody repertoires in a population-based setting using the SHIP-TREND cohort

The Study of Health in Pomerania (SHIP) is a comprehensive population-based project that investigates the health dynamics of the population of Northeast Germany, a region historically associated with lower life expectancy. SHIP"s extensive data collection, including omics data, provides a longitudinal perspective on health trends, enabling the analysis of the complex interplay of biological and environmental factors. As one example, recently the human immune response to Staphylococcus aureus (S. aureus) was measured using the dilution-based multiplexed bead array to monitor antigen-specific IgG and IgA responses across the SHIP-TREND-0 cohort. The findings revealed a highly heterogeneous antibody response influenced by factors such as colonization status, sex, age and health indicators. This uncovered the complexity of the immune response to S. aureus, which ranges from unnoticed colonization to severe infections.

We now expanded the study to track the antibody response to 34 pathogens associated with human infections, such as pneumonia, sepsis, endocarditis and joint infections. We recorded the profile of the antibody response to these bacteria in the SHIP-TREND cohort using the Infection-Array and then later examined its correlation with the composition of the human microbiome and disease risks.

The Infection-Array comprises antigens of the secretomes of these 34 pathogens, including staphylococci, streptococci and members of the Enterobacteriaceae, which are conjugated to individual bead species. Incubation of serum samples in seven-step dilution series with the multiplexed beads allow the binding of the serum antibodies to their respective presented antigens over a high dynamic range. This binding is detected through the addition of a secondary R-phycoerythrin-conjugated antibody, which induces a fluorescence signal, measured with the Luminex® Flexmap 3D® technology. In total, 1307 serum samples of the SHIP-TREND (0 and 1) and SHIP-START (2 and 3) cohorts from different time points (0/1 as baseline and 2/3 as follow-up, respectively) were included in the analysis to also gain a longitudinal perspective on antibody titers in the general population. These studies offer valuable insights into the dynamics of human health and immune responses in the general population as well as data on the association of antibody signals with microbiome composition and different phenotypes.