Tu118 - Early Immune Responses to sars-cov-2 Mrna Vaccination in the Skin of Patients on B-cell Depletion Therapy

Hiromitsu Asashima – Neurology and Immunology – Yale School of Medicine; Noah Lee – Immunobiology and Pathology – Yale School of Medicine; Nicholas Buitrago-Pocasangre – Neurology and Immunobiology – Yale School of Medicine; He Chuan – Neurology and Immunology – Yale School of Medicine; Carlotta Schieler – Immunobiology and Pathology – Yale School of Medicine; Edel Aron – Immunobiology and Pathology; Khadir Raddassi – Neurology and Immunobiology – Yale School of Medicine; Erin Longbrake – Neurology and Immunobiology – Yale School of Medicine; Steven Kleinstein – Immunobiology and Pathology; Mary Tomayko – Dermatology – Yale School of Medicine; David Hafler – Neurology and Immunobiology – Yale School of Medicine

Abstract Text: In contrast to robust immune response to SARS-CoV-2 mRNA vaccination in healthy individuals, patients on B-cell depletion therapy often fail to mount antibody responses but make robust T cell responses. We aim to describe early innate and adaptive immune response in B-cell depleted individuals to better inform clinical decision making in these vulnerable patients. Here 22 subjects (10 B-cell depleted and 12 controls) received secondary mRNA-based vaccines against COVID-19 and underwent skin biopsies near the vaccination site and on the contralateral arm 1-3 days post yielding 42 total samples. Skin tissue was cryopreserved and underwent single cell RNA-sequencing with VDJ repertoire immune profiling. Samples were grouped by vaccination and immune status. Integration of all samples showed 22 clusters of 169,361 total cells with no significant difference in the proportion of vaccinated to unvaccinated cell subpopulations between groups. Dendritic cells in vaccinated skin across all groups demonstrated increased genetic expression of genetic regulator STAT1, complement factor C1QA, maturation markers IDO1, high affinity immunoglobulin gamma Fc receptor FCGR1A and IFN response related genes GBP1 and GBP2. Similarly, macrophages demonstrated increased gene expression of STAT1, GBP1 and GBP4, and FCGR1A in vaccinated skin. These markers are consistent with activated gene profiles in antigen presenting cells in post-vaccinated skin. Furthermore, B cells in vaccinated skin of B-cell depleted patients exhibited increased TNF signaling relative to healthy counterparts. The prevalence of B-cells was comparable to healthy controls. Analysis of T cell receptor repertoire and cell-cell interactions are ongoing and will further elucidate local responses post-vaccination.