TY - JOUR
T1 - 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
AU - Fisher, Devin G.
AU - Gnazzo, Victoria
AU - Holthausen, David J.
AU - López, Carolina B.
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/11/28
Y1 - 2022/11/28
N2 - 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.
AB - 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.
KW - Adjuvant
KW - Defective viral genome-derived oligonucleotide (DDO)
KW - Type 1 immunity
KW - Type I interferon
KW - Vaccine
KW - Virus
UR - http://www.scopus.com/inward/record.url?scp=85141228195&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2022.10.052
DO - 10.1016/j.vaccine.2022.10.052
M3 - Article
C2 - 36333225
AN - SCOPUS:85141228195
SN - 0264-410X
VL - 40
SP - 7270
EP - 7279
JO - Vaccine
JF - Vaccine
IS - 50
ER -