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.
We have published extensively on how vaccine adjuvants can elicit robust cellular immunity. In the process, we recently observed that T cell responses to subunit-based vaccination require many factors not required in T cells responding to infections. This data made us wonder whether or not the T cells are using similar or different sets of genes to achieve the same goal; dramatic expansion and formation of memory. The typical methods we to ask questions about the internal gene expression programs inside cells of interest cannot be used to answer this question as specifically as we need to, so we propose to use a newer technique called single cell RNA sequencing (scRNAseq). This avoids the way other techniques average across all T cell populations, allowing us to measure the diversity of the response to individual immunological challenges. Ultimately, this will determine whether or not vaccine adjuvants make an entirely unique type of T cell and whether or not that information will be useful in discovering and developing better vaccines.
