Dissecting the Heterogeneity of DENV Vaccine-elicited Cellular Immunity Using Single-cell RNA Sequencing and Metabolic Profiling

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Aug 16

PMID 31413301

Citations 33

Authors

Adam T Waickman

Kaitlin Victor

Tao Li

Kristin Hatch

Wiriya Rutvisuttinunt

Carey Medin

Benjamin Gabriel

Richard G Jarman

Heather Friberg

Jeffrey R Currier

Affiliations

Soon will be listed here.

Abstract

Generating effective and durable T cell immunity is a critical prerequisite for vaccination against dengue virus (DENV) and other viral diseases. However, understanding the molecular mechanisms of vaccine-elicited T cell immunity remains a critical knowledge gap in vaccinology. In this study, we utilize single-cell RNA sequencing (scRNAseq) and longitudinal TCR clonotype analysis to identify a unique transcriptional signature present in acutely activated and clonally-expanded T cells that become committed to the memory repertoire. This effector/memory-associated transcriptional signature is dominated by a robust metabolic transcriptional program. Based on this transcriptional signature, we are able to define a set of markers that identify the most durable vaccine-reactive memory-precursor CD8 T cells. This study illustrates the power of scRNAseq as an analytical tool to assess the molecular mechanisms of host control and vaccine modality in determining the magnitude, diversity and persistence of vaccine-elicited cell-mediated immunity.

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