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Rheumatology (Oxford). 2016 Oct;55(10):1901-5. doi: 10.1093/rheumatology/kew262. Epub 2016 Jun 28.

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.

Author information

1
Institut de Recherche Expérimentale et Clinique, Pôle de pathologies rhumatismales inflammatoires et systémiques, Université catholique de Louvain.
2
Institut de Recherche Expérimentale et Clinique, Pôle de pathologies rhumatismales inflammatoires et systémiques, Université catholique de Louvain Département de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
3
Neovacs, Paris.
4
Clinical Immunology and Therapeutic of Osteoarticular Diseases Unit, Department of Rheumatology, Hôpital Lapeyronie, Montpellier.
5
Department of Internal Medicine, Hôpital de Haut Levêque, CHU Bordeaux, Pessac, France.
6
Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
7
Neovacs, Paris gvogel@neovacs.com.

Abstract

OBJECTIVE:

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.

METHODS:

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-IFNα Ab titres, and perform high-throughput transcriptomic studies.

RESULTS:

Neutralization studies of 13 IFNα 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-IFNα Ab titres and decrease in IFN scores compared to baseline. These analyses also revealed an inhibitory effect of IFNα blockade on the expression of B cell associated transcripts.

CONCLUSIONS:

IFN-K induces a polyclonal anti-IFNα response that decreases IFN- and B cell-associated transcripts.

TRIAL REGISTRATION:

ClinicalTrials.gov, clinicaltrials.gov, NCT01058343.

KEYWORDS:

B cells; interferon alpha; interferon alpha kinoid; interferon signature; systemic lupus erythematosus

PMID:
27354683
PMCID:
PMC5034220
DOI:
10.1093/rheumatology/kew262
[Indexed for MEDLINE]
Free PMC Article

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