Barcode Enabled Antigen Mapping (BEAM) enables next-generation systems immunology analysis of the post-COVID-19 immune landscape

Abstract

Abstract A more complete understanding of immune responses to disease requires consideration of multiple different cell types across both the innate and adaptive branches of the immune system along with the detection of many different analytes. We used Barcode Enabled Antigen Mapping (BEAM) and Immune Profiling technology to perform simultaneous multimodal profiling at single cell resolution in hundreds of thousands of peripheral blood mononuclear cells (PBMCs) from a human donor following recovery from COVID-19. In addition to measuring gene and protein expression, we generated full-length, paired sequences of the rearranged T- and B-cell receptors while also screening their specificity for a wide range of antigens from SARS-CoV-2 and other viral pathogens. These data provide insights into the entirety of the immune landscape after recovery from acute viral disease. The scale and throughput of our experiments gave us high-resolution data from all cell types from the innate and adaptive immune systems. We identified antigen-specific clones of both B and T lymphocytes, with the high cellular throughput enabling detection of rare clones. Analysis of all PBMC cell types allowed us to place these antigen-specific clones within the overall transcriptional landscape of the post-viral immune system. Experiments such as these will underpin new systems immunology approaches and will continue to reveal the complex interplay between the components of the immune system. We envisage that these methods will be valuable in the analysis of the immune response to vaccination, infectious disease, cancer, allergy, autoimmune conditions, and ageing that can potentially lead to the development of novel diagnostic and therapeutic approaches.