Interferon α kinoid induces neutralizing anti-interferon α antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts …
J Ducreux, FA Houssiau, P Vandepapeliere… - …, 2016 - academic.oup.com
Rheumatology, 2016•academic.oup.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 …
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 …
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
Oxford University Press