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

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

doi:10.18632/oncotarget.23725

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Journal article

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

Oberson, Anne Pharmacology, Department of Medicine, Faculty of Science, University of Fribourg, Switzerland
Spagnuolo, Lorenzo Pharmacology, Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - School of Pharmaceutical Sciences, University of Geneva, Switzerland - Department of Anesthesiology, Pharmacology and Intensive Care, Faculty of Medicine, University of Geneva, Switzerland
Puddinu, Viola School of Pharmaceutical Sciences, University of Geneva, Switzerland - Department of Anesthesiology, Pharmacology and Intensive Care, Faculty of Medicine, University of Geneva, Switzerland
Barchet, Winfried German Center for Infection Research, Cologne-Bonn, Germany - Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Germany
Rittner, Karola Transgene S.A., Parc d?Innovation, Illkirch-Graffenstaden, France
Bourquin, Carole Pharmacology, Department of Medicine, Faculty of Science, University of Fribourg, Switzerland - School of Pharmaceutical Sciences, University of Geneva, Switzerland - Department of Anesthesiology, Pharmacology and Intensive Care, Faculty of Medicine, University of Geneva, Switzerland

19.01.2018

Published in:

Oncotarget. - 2018, vol. 9, no. 5, p. 5641-5651

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language