Dissecting the heterogeneity of DENV vaccine-elicited cellular immunity using single-cell RNA sequencing and metabolic profiling

Adam T. Waickman (), Kaitlin Victor, Tao Li, Kristin Hatch, Wiriya Rutvisuttinunt, Carey Medin, Benjamin Gabriel, Richard G. Jarman, Heather Friberg and Jeffrey R. Currier
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Adam T. Waickman: Walter Reed Army Institute of Research
Kaitlin Victor: Walter Reed Army Institute of Research
Tao Li: Walter Reed Army Institute of Research
Kristin Hatch: Walter Reed Army Institute of Research
Wiriya Rutvisuttinunt: Walter Reed Army Institute of Research
Carey Medin: University of Rhode Island
Benjamin Gabriel: University of Rhode Island
Richard G. Jarman: Walter Reed Army Institute of Research
Heather Friberg: Walter Reed Army Institute of Research
Jeffrey R. Currier: Walter Reed Army Institute of Research

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11634-7

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