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

项目摘要 对实验性或FDA批准的疫苗佐剂制剂的临床相关细胞应答 难以产生和/或检测。鉴于针对感染性挑战的强有力的细胞应答， 一个合理的假设是，亚单位疫苗制剂将更好地实现细胞应答， 管理对感染的反应的既定规则。然而，我们已经证明亚单位疫苗- 引发的T细胞应答依赖于许多因素（细胞因子、转录因子、代谢调节因子、免疫调节因子和免疫调节因子）。 途径），其与T细胞对感染性攻击的应答无关，甚至是限制性的。最近 初步的scRNAseq结果表明，亚单位疫苗接种产生了一个完全独特的T细胞群， 对感染性攻击反应不明显的细胞，能够快速、稳健和持久的记忆 阵目前的建议将检查疫苗引起的和感染引起的T细胞的异质性， 细胞反应随时间的变化，这种异质性相互重叠的程度，以及是否 特异性T细胞群预示佐剂诱导T细胞的能力，因此可用于 使佐剂沿着保护性CD 8 + T细胞记忆产生的轴分层。

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.