1190-P: IFN-Alpha Kinoid: A Promising Vaccine against Type 1 Diabetes Targeting IFN-alpha in NOD Mice

Abstract

Major elements highlight IFNα implication in type 1 diabetes (T1D) pathogenesis. While there is still no cure for this autoimmune disease, we aimed to evaluate the benefit of IFNα kinoid (IFN-K). This conjugated vaccine consisting of IFNα coupled to Keyhole limpet hemocyanin as a carrier protein elicits the production of polyclonal anti-IFNα neutralizing antibodies and has shown beneficial effects in a recent phase IIb trial in lupus (NCT02665364). Three independent experiments in NOD mice were performed to evaluate the activity of anti-IFNα neutralizing antibodies, conveyed either by maternal transfer or by passive or active immunization. Glycemia was monitored by a glucometer, neutralizing antibodies by the virus-induced cytopathic effect assay and H&E pancreas sections were evaluated in blind. In the first study, we compared T1D incidence in offsprings from IFN-K or KLH immunized mothers with sentinels. In the second study, mice were passively immunized with purified total IgG from sera collected in NOD mice immunized with IFN-K or KLH. Finally, active immunization was performed with IFN-K, KLH or PBS in combination with a squalene oil-in-water adjuvant. Mice were immunized at 5, 10 or 15 weeks of age. Anti-IFNα neutralizing antibodies were effectively conveyed from mothers to offspring, and levels decreased over time to completely disappear by month 3. In progeny from IFN-K immunized mice, despite transient and low amount of neutralizing antibodies, insulitis was decreased compared to control groups and T1D onset was delayed. In the second study, long-lasting administrations of total IgG comprising anti-IFNα neutralizing antibodies conferred protection towards T1D development, while total IgG from KLH-immunized mice did not. Finally, diabetes incidence was reduced when IFN K immunization started at week 10 of age. These different elements point out the need to neutralize IFNα during NOD lifetime to prevent T1D, and encourage us to evaluate IFN-K in newly diagnosed T1D patients. Disclosure N. Caillot: None. F. Colaone: None. R. Bertrand: None. J. Da Silva: None. S. Hamdi: None. J. Bonnefoy: None. A. Lehuen: Board Member; Spouse/Partner; Inatheris. Consultant; Self; Neovacs. B.F. Boitard: None. G. Grouard-Vogel: None.