2025-05-14 ミュンヘン大学(LMU)
<関連情報>
- https://www.lmu.de/en/newsroom/news-overview/news/yellow-fever-vaccination-how-strong-immune-responses-are-triggered.html
- https://www.pnas.org/doi/10.1073/pnas.2422236122
黄熱ワクチン接種による樹状細胞と単球のインターフェロン誘導活性化は初期抗体応答と相関する Interferon-induced activation of dendritic cells and monocytes by yellow fever vaccination correlates with early antibody responses
Elena Winheim, Antonio Santos-Peral, Tamara Ehm, +10 , and Anne B. Krug
Proceedings of the National Academy of Sciences Published:May 7, 2025
DOI:https://doi.org/10.1073/pnas.2422236122
Significance
The yellow fever vaccine is one of the most successful vaccines available. After a single dose, it induces long-lasting protective immunity against yellow fever, a severe disease caused by the yellow fever virus which is transmitted by mosquitoes. It is not clear why this live vaccine is so exceptionally efficient. Antigen-presenting cells (APCs) are crucial for the induction of immunity against viral infection. We therefore investigated the early response of APC subpopulations in the blood of healthy vaccinees and found that a specific activation state of APCs induced by interferons was associated with the early production of protective antibodies.
Abstract
Yellow fever vaccination provides long-lasting protection and is a unique model for studying the immune response to an acute RNA virus infection in humans. To elucidate the early innate immune events preceding the rapid generation of protective immunity, we performed transcriptome analysis of human blood dendritic cell (DC) and monocyte subpopulations before and 3, 7, 14, and 28 d after vaccination. We detected temporary upregulation of IFN-stimulated genes (ISG) in all DC and monocyte subsets on days 3 and 7 after vaccination as well as cell type–specific responses and response kinetics. Single-cell RNA sequencing revealed rapid appearance of activated DC and monocyte clusters dominated by ISGs, inflammatory chemokines, and genes involved in antigen processing and presentation. This was confirmed by flow cytometric analysis in a large cohort of vaccinees. We identified SIGLEC1/CD169 upregulation as a sensitive indicator of the transient IFN-induced activation state elicited in DCs and monocytes by YF17D vaccination correlating with early protective IgM antibody responses.
