The detection and quantification of human antibody levels directed against specific antigens is of utmost importance in several fields ranging from healthcare diagnostics, vaccine development, and immunological research to analysis of disease mechanisms. We have developed a serological xMAP® approach (xMAPr), which is superior over a classical one-stage dilution approach by generating high-dynamic range (HDR) data, by dramatically increasing in the dynamic range of over three magnitudes of order. This methodology was used in a population-based setting (SHIP cohort, N=996) to analyze different antibody isotype responses directed against 80 antigens derived from Staphylococcus aureus. The results were analyzed in  combination with different phenotypes and other Omics data revealing new insights in the S. aureus-specific immune response in healthy individuals.