Exploring the heterogeneity of the vaccine-elicited T cell response by scRNAseq

PROJECT SUMMARY Clinically relevant cellular responses to either experimental or FDA approved vaccine adjuvant formulations have been difficult to generate and/or detect.

Given the robust cellular responses against infectious challenge, a reasonable assumption is that subunit vaccine formulations will better achieve cellular responses by following the established rules governing the response to infections.

However, we have shown that subunit vaccine- elicited T cell responses are dependent on numerous factors (cytokines, transcription factors, metabolic pathways) which are irrelevant, or even restrictive, to the T cell response to infectious challenge.

More recent preliminary scRNAseq results suggest that subunit vaccination generates an entirely unique population of T cells unobserved in response to infectious challenge, capable of rapid, robust, and enduring memory formation.

The present proposal will examine the heterogeneity of both vaccine-elicited and infection-elicited T cell responses over time, to what degree this heterogeneity overlaps with each other, and whether or not specific T cell populations are predictive of an adjuvants' capacity for eliciting T cells and therefore be useful in stratifying adjuvants along the axis of protective CD8+ T cell memory generation.