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

Anne Oberson; Lorenzo Spagnuolo; Viola Puddinu; Winfried Barchet; Karola Rittner; Carole Bourquin

doi:10.18632/oncotarget.23725

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

Oncotarget. 2017 Dec 15;9(5):5641-5651. doi: 10.18632/oncotarget.23725. eCollection 2018 Jan 19.

Authors

Anne Oberson¹, Lorenzo Spagnuolo^{1

2

3}, Viola Puddinu^{2

3}, Winfried Barchet^{4

5}, Karola Rittner⁶, Carole Bourquin^{1

2

3}

Affiliations

¹ Chair of Pharmacology, Department of Medicine, Faculty of Science, University of Fribourg, 1700 Fribourg, Switzerland.
² School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland.
³ Department of Anesthesiology, Pharmacology and Intensive Care, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
⁴ German Center for Infection Research, Cologne-Bonn, Germany.
⁵ Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Germany.
⁶ Transgene S.A., Parc d'Innovation, CS80166, 67405 Illkirch-Graffenstaden Cedex, France.

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.

Keywords: NAB2; cancer immunotherapy; interferon; pattern-recognition receptors; poly(I:C).