Quantitative assessment of multiple pathogen exposure and immune dynamics at scale

Serological responses reveal recent and historical exposure to pathogens, as well as the state of autoimmune and other chronic conditions, including cancer. Serological tests either assess one or a few antigens in many people, or multiple antigens for modest sample sizes. Here, we describe a multiplexed serology method that evaluates samples at the scale of thousands. This molecular epidemiology tool operates at a population scale sufficientto evaluate broadly how various infectious exposures or autoimmune responses affecthealth. The method employs full-length folded proteins, is quantitative over a wide dynamic range, and performs favorably compared with commercial clinical assays [severe acute respiratory syndrome coronavirus 2 chemiluminescent IgG II assay (Beckman) and Platelia SARS-CoV-2 total Ab enzyme-linked immunosorbent assay (Bio-Rad, California, USA)]. Responses to 39 bacteria species/strains and 99 viruses in 2,400 people were evaluated. Subjects with longitudinal data showed quantitative stability of response to all antigens over the 6-month time window, enabling the detection of intervening clinical events. We expect this highly adaptable method will findbroad application in immune profiletracking.