NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA.
NIH Center for Human Immunology, NIH, Bethesda, MD 20892, USA; Biometric Research Program, Division of Cancer Treatment and Diagnosis, NCI, NIH, Rockville, MD, USA.
Cell Rep. 2024 Sep 24;43(9):114706. doi: 10.1016/j.celrep.2024.114706. Epub 2024 Sep 4.
To gain insight into how an adjuvant impacts vaccination responses, we use systems immunology to study human H5N1 influenza vaccination with or without the adjuvant AS03, longitudinally assessing 14 time points including multiple time points within the first day after prime and boost. We develop an unsupervised computational framework to discover high-dimensional response patterns, which uncover adjuvant- and immunogenicity-associated early response dynamics, including some that differ post prime versus boost. With or without adjuvant, some vaccine-induced transcriptional patterns persist to at least 100 days after initial vaccination. Single-cell profiling of surface proteins, transcriptomes, and chromatin accessibility implicates transcription factors in the erythroblast-transformation-specific (ETS) family as shaping these long-lasting signatures, primarily in classical monocytes but also in CD8 naive-like T cells. These cell-type-specific signatures are elevated at baseline in high-antibody responders in an independent vaccination cohort, suggesting that antigen-agnostic baseline immune states can be modulated by vaccine antigens alone to enhance future responses.
为了深入了解佐剂如何影响疫苗接种反应，我们使用系统免疫学研究了含有或不含有佐剂 AS03 的人类 H5N1 流感疫苗接种，纵向评估了 14 个时间点，包括首次接种和加强接种后第一天的多个时间点。我们开发了一种无监督的计算框架来发现高维反应模式，这些模式揭示了佐剂和免疫原性相关的早期反应动力学，包括一些在加强接种后与加强接种前不同的反应动力学。有或没有佐剂，一些疫苗诱导的转录模式至少在初始接种后 100 天内持续存在。表面蛋白、转录组和染色质可及性的单细胞分析表明，红细胞生成特异性（ETS）家族中的转录因子在塑造这些持久的特征中起作用，主要在经典单核细胞中，但也在 CD8 幼稚样 T 细胞中。在一个独立的疫苗接种队列中，高抗体应答者的基线中这些细胞类型特异性特征升高，这表明抗原不可知的基线免疫状态可以仅通过疫苗抗原来调节，以增强未来的反应。
