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Interferon ? kinoid induces neutralizing anti-interferon ? antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon ? kinoid phase I/II study.


ABSTRACT: IFN ? Kinoid (IFN-K) is a therapeutic vaccine composed of IFN?2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients. Here, we analysed extended follow-up data from IFN-K-treated patients, in order to evaluate persistence of neutralizing anti-IFN? Abs antibodies (Abs), and gene expression profiling.Serum and whole blood RNA samples were obtained in IFN-K-treated patients included in the follow-up study, in order to determine binding and neutralizing anti-IFN? Ab titres, and perform high-throughput transcriptomic studies.Neutralization studies of 13 IFN? subtypes demonstrated the polyclonal nature of the Ab response induced by IFN-K. Follow-up analyses in six patients confirmed a significant correlation between neutralizing anti-IFN? Ab titres and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFN? blockade on the expression of B cell associated transcripts.IFN-K induces a polyclonal anti-IFN? response that decreases IFN- and B cell-associated transcripts.ClinicalTrials.gov, clinicaltrials.gov, NCT01058343.

SUBMITTER: Ducreux J 

PROVIDER: S-EPMC5034220 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon α kinoid phase I/II study.

Ducreux Julie J   Houssiau Frédéric A FA   Vandepapelière Pierre P   Jorgensen Christian C   Lazaro Estibaliz E   Spertini François F   Colaone Fabien F   Roucairol Camille C   Laborie Marion M   Croughs Thérèse T   Grouard-Vogel Géraldine G   Lauwerys Bernard R BR  

Rheumatology (Oxford, England) 20160628 10


<h4>Objective</h4>IFN α Kinoid (IFN-K) is a therapeutic vaccine composed of IFNα2b coupled to a carrier protein. In a phase I/II placebo-controlled trial, we observed that IFN-K significantly decreases the IFN gene signature in whole blood RNA samples from SLE patients. Here, we analysed extended follow-up data from IFN-K-treated patients, in order to evaluate persistence of neutralizing anti-IFNα Abs antibodies (Abs), and gene expression profiling.<h4>Methods</h4>Serum and whole blood RNA sampl  ...[more]

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