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.
Highlights
Generating effective and durable T cell immunity is a critical prerequisite for vaccination against dengue virus (DENV) and other viral diseases
Moderate CD4+ T cell activation was observed in response to TAK-003 administration (Fig. 1c, d, Supplementary Fig. 1), with the peak of activation observed on day 14 post-vaccination
In this study, we demonstrate that the live-attenuated tetravalent DENV vaccine TAK-003 is capable of eliciting potent and durable cellular immunity
Summary
Generating effective and durable T cell immunity is a critical prerequisite for vaccination against dengue virus (DENV) and other viral diseases. Transcriptional analysis of CD8+ T cells acutely activated in response to TAK-003 exposure revealed a highly diverse transcriptional profile, with NS1- and NS3- reactive memory-precursor CD8+ T cells at day 14 post-immunization displaying a distinct transcriptional signature dominated by metabolic pathways. Based on these observations, we identified a panel of metabolic markers, which could be used to faithfully identify CD8+ T cells activated in vitro in response to antigenic stimulation, or activated in vivo in response to TAK-003. Analysis of the metabolic profile in vaccine-responsive CD8+ T cells can aid in the identification and characterization of the most effective and durable vaccine-elicited clonotypes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
