{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:51:44Z","timestamp":1790718704846,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009505","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000}}],"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovative Medicine Initiative","award":["115924"],"award-info":[{"award-number":["115924"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The Tick-borne encephalitis virus (TBEV) causes different disease symptoms varying from asymptomatic infection to severe encephalitis and meningitis suggesting a crucial role of the human host immune system in determining the fate of the infection. There is a need to understand the mechanisms underpinning TBEV-host interactions leading to protective immunity. To this aim, we studied the response of human peripheral blood mononuclear cells (PBMC) to the whole formaldehyde inactivated TBEV (I-TBEV), the drug substance of Encepur, one of the five commercially available vaccine. Immunophenotyping, transcriptome and cytokine profiling of PBMC revealed that I-TBEV generates differentiation of a sub-population of plasmacytoid dendritic cells (pDC) that is specialized in type I interferon (IFN) production. In contrast, likely due to the presence of aluminum hydroxide, Encepur vaccine was a poor pDC stimulus. We demonstrated I-TBEV-induced type I IFN together with Interleukin 6 and BAFF to be critical for B cell differentiation to plasmablasts as measured by immunophenotyping and immunoglobulin production. Robust type I IFN secretion was induced by pDC with the concerted action of both viral E glycoprotein and RNA mirroring previous data on dual stimulation of pDC by both <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> and influenza virus protein and nucleic acid that leads to a type I IFN-mediated sustained immune response. E glycoprotein neutralization or high temperature denaturation and inhibition of Toll-like receptor 7 signalling confirmed the importance of preserving the functional integrity of these key viral molecules during the inactivation procedure and manufacturing process to produce a vaccine able to stimulate strong immune responses.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009505","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T09:23:57Z","timestamp":1618565037000},"page":"e1009505","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Human plasmacytoid dendritic cells at the crossroad of type I interferon-regulated B cell differentiation and antiviral response to tick-borne encephalitis virus"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2551-393X","authenticated-orcid":true,"given":"Marilena 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