Abstract The immune system is composed of many heterogeneous cell types that respond in a synergistic manner to mount both immediate and long-lived immunity against pathogens. The complexity of the immune system necessitates an integrated view of multiple biological modalities to understand different roles of varying cell types of the immune system. Detailed transcriptomic and protein analysis at the single cell level is essential to follow the immune system’s response to pathogens in mounting an antigen specific response. With heavy emphasis on assays that facilitate the analysis of antigen-specific cellular and humoral immune responses, the Integrative Multi-Omics Core will serve as a resource to standardize, optimize, and perform multi-omic single cell research to support the biological research objectives of Projects 1, 2 and 3. The implementation of highly standardized and automated assays will enable longitudinal and cross-sectional analysis of the human samples within and across the research projects. Specifically, the core will provide: i. standardized high throughput flow cytometry, bulk transcriptomics and plasma proteomics; ii. well established synergistic assays for the analysis of antigen-specific T cell and B cell responses, including several orthogonal approaches for profiling antigen-specific T cells and a range of systems serology assays; and iii. optimized cost-efficient single-cell sequencing multi-omics methods for analysis of cellular protein-expression, gene-expression, adaptive receptor sequences, antigen-specificity, and epigenomics based on the 10x Genomics platform. Furthermore, we will use a collaborative cloud environment to support data ingest, processing and provision to the DMAC for deposition into ImmPort in support of rapid public access and innovation in data integration and visualization.