NAB2 is a novel immune stimulator of MDA-5 that promotes a strong type I interferon response

Oncotarget
Anne ObersonCarole Bourquin

Abstract

Novel adjuvants are needed to increase the efficacy of vaccine formulations and immune therapies for cancer and chronic infections. In particular, adjuvants that promote a strong type I IFN response are required, since this cytokine is crucial for the development of efficient anti-tumoral and anti-viral immunity. Nucleic acid band 2 (NAB2) is a double-stranded RNA molecule isolated from yeast and identified as an agonist of the pattern-recognition receptors TLR3 and MDA-5. We compared the ability of NAB2 to activate innate immunity with that of poly(I:C), a well-characterized TLR3 and MDA-5 agonist known for the induction of type I IFN. NAB2 promoted stronger IFN-α production and induced a higher activation state of both murine and human innate immune cells compared to poly(I:C). This correlated with a stronger activation of the signalling pathway downstream of MDA-5, and IFN-α induction was dependent on MDA-5. Upon injection, NAB2 induced higher levels of serum IFN-α in mice than poly(I:C). These results suggest that NAB2 has the potential to become an efficient adjuvant for the induction of type-I IFN responses in therapeutic immunization against cancer or infections.

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Citations

Sep 27, 2019·Nature Reviews. Drug Discovery·Claire Vanpouille-BoxLorenzo Galluzzi
Nov 19, 2019·Trends in Immunology·Felix Streicher, Nolwenn Jouvenet

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Methods Mentioned

BETA
transfection
ELISA
flow cytometry
transfections
FACS

Software Mentioned

Tree Stat
FlowJo
GraphPad Prism

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