A1 Refereed original research article in a scientific journal
COVID-19 vaccine type controls stromal reprogramming in draining lymph nodes
Authors: Fair-Mäkelä, Ruth; Thorén, Pinja; Näsiaho, Joni; Sundqvist, Pia; Piiroinen, Irina; Kähäri, Laura; Julkunen, Ilkka; Ivaska, Johanna; Hub, Elin; Rot, Antal; Ghimire, Bishwa; Alanko, Jonna; Salmi, Marko
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Publishing place: WASHINGTON
Publication year: 2025
Journal: Science Immunology
Journal acronym: SCI IMMUNOL
Article number: eadr6787
Volume: 10
Issue: 110
Number of pages: 20
eISSN: 2470-9468
DOI: https://doi.org/10.1126/sciimmunol.adr6787
Web address : https://www.science.org/doi/10.1126/sciimmunol.adr6787
Lymph node (LN) stromal cells are critical regulators of immune reactions, yet their responses to different SARS-CoV-2 vaccines remain unexplored. Here, we immunized mice with clinically approved gene- and protein-based COVID-19 vaccines targeting viral spike (S) protein and analyzed the draining LN stroma using multimodal bioimaging, single-cell transcriptomics, and functional studies. We found that messenger RNA and adenovirus vector vaccines transfected lymphatic endothelial cell and fibroblastic reticular cell subsets in vivo and led to early local S protein production in the draining LN in a vaccine-specific manner. The vaccines induced rapid transcriptomic reprogramming of the LN stromal cells, which functionally altered scavenging and parenchymal transfer of lymph-borne antigens, formation of chemokine gradients, and migration of eosinophils within LNs. Thus, distinct vaccine formulations targeting S protein differentially prime the draining LN stromal cells before the arrival of migratory dendritic cells bearing immunogens.
Funding information in the publication:
This research was supportedby Research council of Finland grants 347202 (R.F.-M), 346131 (J.i.), 362007 (J.A.), and 336422(M.S.); Research council of Finland inFlAMeS Flagship grants 337530, 357910, and 358823;instrumentarium Science Foundation (J.A.); Sigrid Juselius Foundation grant (M.S.); and Sakari Alhopuro Foundation grants 20210041 and 20220168 (R.F.-M.).
