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

通过 scRNAseq 探索疫苗引发的 T 细胞反应的异质性

基本信息

批准号：
10218805
负责人：
Ross M Kedl
金额：
$ 23.33万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-28 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10218805
关键词：
ATAC-seq Adjuvant Agreement Algorithms Attenuated Vaccines B-Lymphocytes Bioinformatics Biology CD8-Positive T-Lymphocytes Cell physiology Cells Cellular Immunity Cellular biology Chromatin Cluster Analysis Data Data Set Dependence Dimensions FDA approved Formulation Gene Expression Gene Expression Profile Generations Genes Genetic Transcription Goals Herpesvirus 1 Heterogeneity Human Immune Immune response Immunity Immunization Immunologics Individual Infection Infectious Agent Interleukin-15 Light Listeria monocytogenes Lymphocytic choriomeningitis virus Maintenance Measures Mediating Memory Metabolic Metabolic Pathway Methods Modeling Molecular Mus Oxidative Phosphorylation Pathology Phenotype Population Process Publishing Subunit Vaccines T cell response T memory cell T-Cell Activation T-Lymphocyte T-Lymphocyte Subsets Techniques Testing Time Vaccination Vaccine Adjuvant Vaccines Vaccinia virus Yellow Fever Vaccine base clinically relevant cytokine interest mouse model population based programs response self-renewal single-cell RNA sequencing transcription factor transcriptome sequencing transcriptomics vaccine development

项目摘要

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.

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，随着时间的推移，细胞反应，这种异质性彼此重叠的程度，以及是否特异性T细胞群预示佐剂诱导T细胞的能力，因此可用于沿着保护性CD 8 + T细胞记忆产生的轴对佐剂进行分层。