W173 - Integrated Transcriptomic and Immune Repertoire Analysis Reveals Innate and Adaptive Immune Response to Vaccination

Lester Kobzik – Cellecta, Inc.; Tianbing Liu – Cellecta, Inc.; Dongfang Hu – Cellecta, Inc.; Mikhail Makhanov – Cellecta, Inc.; Kitt Paraiso – Cellecta, Inc.; Khadija Ghias – Cellecta, Inc.; Paul Diehl – Cellecta, Inc.

Abstract Text: We present an examination of immunological responses elicited by Td (Tetanus-diphtheria), PPSV23 (pneumococcal), and Shingrix (herpes zoster) vaccines. Utilizing techniques for genome-wide expression and adaptive immune receptor (AIR) profiling, along with single-cell transcriptome analysis of isolated T and B cells, we present the temporal landscape of the immune response, post-vaccination. Blood samples were collected from a single donor, pre- and post-vaccination, employing Mitra microsampling technology and Tempus tubes for sample collection. RNA and DNA were extracted, and the DriverMap™ targeted RNA-Seq expression profiling assay was used for genome-wide profiling (19K panel), and DriverMap™ AIR immune repertoire profiling assay run to profile T and B cell receptors from RNA and DNA. The NGS results were analyzed using the MiXCR (MiLaboratories) pipeline (AIR panel) and Salmon analysis (targeted RNA-Seq 19K panel). Pathway enrichment analysis of the whole transcriptome shows that innate immune response, with significant activation of interferon and cytokine signaling, is prominent on Day 2 after immunization, followed by activation of adaptive immunity on Days 7-10, which gradually declines to baseline levels by Days 15-22. Adaptive immune responses to vaccinations involved both branches of TCR and BCR signaling with significant activation of immunoglobulin clonotypes specific for vaccine antigens. A detailed characterization of specific cell types responsible for adaptive immune responses was obtained through T/B cell sorting experiments and 10x Genomics analysis. This study highlights the importance of integrated transcriptome, immune repertoire, and single-cell analysis profiling to monitor the response to vaccination in understanding the complex interplay of innate and adaptive immunity.