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 provides a longitudinal perspective on health trends, enabling the analysis of the complex interplay of biological and environmental factors. For instance, Staphylococcus aureus (S. aureus)-specific IgG and IgA responses were measured using a dilution-based multiplexed bead array to monitor the immune response across the SHIP-TREND-0 cohort. The findings revealed a heterogeneous antibody response to different S. aureus antigens influenced by factors such as colonization status, sex, and age.

We now expanded the study to track the antibody response to 35 pathogens associated with human infections, such as pneumonia, sepsis, 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 examined its correlation with the composition of the microbiome.

The Infection Array comprises antigens of the secretomes of these pathogens, which are conjugated to individual bead species. Incubation of plasma samples in seven-step dilution series with the multiplexed beads allow the binding of the plasma antibodies to their respective presented antigens over a high dynamic range. The binding is detected via the addition of a secondary R-phycoerythrin-conjugated antibody, which induces a fluorescence signal that is measured with the Luminex® Flexmap 3D®. In total, 2041 plasma samples of the SHIP-TREND (0 and 1) and SHIP-START (2 and 3) cohorts (0/1 as baseline and 2/3 as follow-up) were included in the analysis to gain a longitudinal perspective on pathogen-specific antibody titers. The studies offered valuable insights into the dynamics of health in the general population as male sex is associated with higher S. aureus carriage and female sex correlates with higher antibody responses against uropathogenic bacteria. With increasing age there is a slightly negative correlation with pathogens that cause vaccine-preventable diseases such as Streptococcus pneumoniae and Haemophilus influenzae, thereby indicating a decrease in the efficiency of the immune system.

These findings highlight how age, sex, or colonization status shape pathogen-specific antibody responses, revealing important insights into immune dynamics within the population.