Non-standard viral genome-derived RNA activates TLR3 and type I IFN signaling to induce cDC1-dependent CD8+ T-cell responses during vaccination in mice

Devin G. Fisher, Victoria Gnazzo, David J. Holthausen, Carolina B. López

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

There is a critical need to develop vaccine adjuvants that induce robust immune responses able to protect against intracellular pathogens, including viruses. Previously, we described defective viral genome-derived oligonucleotides (DDOs) as novel adjuvants that strongly induce type 1 immune responses, including protective Th1 CD4+ T-cells and effector CD8+ T-cells in mice. Here, we unravel the early innate response required for this type 1 immunity induction. Upon DDO subcutaneous injection, type 1 conventional dendritic cells (cDC1s) accumulate rapidly in the draining lymph node in a Toll-like receptor 3 (TLR3)- and type I interferon (IFN)-dependent manner. cDC1 accumulation in the lymph node is required for antigen-specific CD8+ T-cell responses. Notably, in contrast to poly I:C, DDO administration resulted in type I IFN expression at the injection site, but not in the draining lymph node. Additionally, DDOs induced an inflammatory cytokine profile distinct from that induced by poly I:C. Therefore, DDOs represent a powerful new adjuvant to be used during vaccination against intracellular pathogens.

Original languageEnglish
Pages (from-to)7270-7279
Number of pages10
JournalVaccine
Volume40
Issue number50
DOIs
StatePublished - Nov 28 2022

Keywords

  • Adjuvant
  • Defective viral genome-derived oligonucleotide (DDO)
  • Type 1 immunity
  • Type I interferon
  • Vaccine
  • Virus

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