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

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Research Papers: Immunology:

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 and Carole Bourquin _

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Oncotarget. 2018; 9:5641-5651. https://doi.org/10.18632/oncotarget.23725

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Abstract

Anne Oberson1,*, Lorenzo Spagnuolo1,2,3,*, Viola Puddinu2,3, Winfried Barchet4,5, Karola Rittner6 and Carole Bourquin1,2,3

1Chair of Pharmacology, Department of Medicine, Faculty of Science, University of Fribourg, 1700 Fribourg, Switzerland

2School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211 Geneva, Switzerland

3Department of Anesthesiology, Pharmacology and Intensive Care, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland

4German Center for Infection Research, Cologne-Bonn, Germany

5Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Germany

6Transgene S.A., Parc d’Innovation, CS80166, 67405 Illkirch-Graffenstaden Cedex, France

*These authors contributed equally to this work

Correspondence to:

Carole Bourquin, email: [email protected]

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

Received: April 13, 2017 Accepted: October 13, 2017 Published: December 15, 2017

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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Research Papers: Immunology:

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

Abstract