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

项目总结 对实验性或FDA批准的疫苗佐剂制剂的临床相关细胞反应 已经很难生成和/或检测。鉴于针对感染挑战的强大细胞反应， 一个合理的假设是，亚单位疫苗配方将通过以下方式更好地实现细胞应答 管理对感染的反应的既定规则。然而，我们已经证明了亚单位疫苗- 激发的T细胞反应依赖于许多因素(细胞因子、转录因子、代谢 途径)与T细胞对感染攻击的反应无关，甚至是限制性的。更近的 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细胞群体 对感染性挑战无反应的细胞，能够快速、强健和持久的记忆 队形。目前的建议将检查疫苗诱导和感染诱导T细胞的异质性。 细胞随时间的反应，这种异质性彼此重叠的程度，以及是否 特定的T细胞群可以预测佐剂诱导T细胞的能力，因此在 沿着保护性CD8 T细胞记忆生成的轴分层佐剂。

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.