Summary The main goals of the Supplement Award are to (1) correlate immunoserological responses to early immune reactions in local tissue environment of the vaccine injection site in healthy donors, and (2) the compare between healthy controls and patients with hematological disorders or autoimmune disease. We will use a high plex immuno-fluorescence CODEX imaging panel to profile these skin biopsy samples in the next year of the award. Using this panel, we can confirm the expression of the SARS-CoV-2 Spike antigen. Interestingly, the SARS-CoV- 2 Spike antigen was detected in the epidermis and dermis of both arms from two donors. Specifically, SARS- CoV-2 Spike co-expressed with CD303 and CD63 of the unvaccinated arm tissue of a healthy donor and in cluster 0 of the vaccinated arm of a BCD donor, indicating expression in dendritic cells and basophils. In the next year to be supported by the Supplement Award, we will be imaging at least 13 more skin tissue sections and plan to conduct deeper informatics analysis. Additionally, we are performing DBiT-based spatial CITE-seq on adjacent slides from these 13 skin tissue sections and integrating the data with previously obtained sc-mRNA- seq data. Furthermore, we have completed immunoserology assays with the serum samples of these donors and patients. Therefore, once we complete the peripheral tissue spatial imaging and spatial omics sequencing, the results will be compared to systemic immunological and serological responses over times to help understand the role of early immune reaction in the development of an effective vaccine protection, in particular, in patients with blood cancer or autoimmune disease.

Project Narrative This supplement project aims to develop and apply immuno-serological assays and single-cell spatial omics assays to investigate the COVID 19 vaccine response in patients with hematologic malignancies and autoimmunity. The findings will improve our understanding of innate and adaptive immune mechanisms in COVID-19 vaccination and provide insights for how to prevent or intervene in future infectious disease pandemic or epidemic, in particular, for protecting patients with compromised immunity.