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Active immunisation of human interferon α transgenic mice with a human interferon α Kinoid induces antibodies that neutralise interferon α in sera from patients with systemic lupus erythematosus
  1. Alexis Mathian1,2,3,
  2. Zahir Amoura1,2,3,
  3. Estelle Adam4,
  4. Fabien Colaone4,
  5. Marco F M Hoekman5,
  6. Olivier Dhellin4,
  7. Pierre Vandepapelière4,
  8. Julien Haroche1,
  9. Jean-Charles Piette1,
  10. Pierre Lebon6,7,
  11. Géraldine Grouard-Vogel4
  1. 1Service de Médecine Interne, Centre de Référence National pour les Lupus et le Syndrome des Antiphospholipides, CHU Pitié-Salpêtrière, APHP, Paris, France
  2. 2Université Pierre et Marie Curie, UPMC Univ. Paris 06, Paris, France
  3. 3Institut National de la Santé et de la Recherche Médicale, INSERM UMR-S 945, Paris, France
  4. 4Neovacs SA, Paris, France
  5. 5Transgenic Facility, Utrecht University, GDL, Utrecht, The Netherlands
  6. 6Hôpital Saint Vincent de Paul-Cochin, APHP, Paris, France
  7. 7Université Paris Descartes, Univ. Paris 05, Paris, France
  1. Correspondence to Dr Géraldine Grouard-Vogel, Neovacs, 3-5, Impasse Reille, 75014 Paris, France; gvogel{at}neovacs.com

Abstract

Objectives Interferon α (IFNα) plays a central role in the pathogenesis of systemic lupus erythematosus (SLE) and is considered a target for its treatment. In the current study, the ability of active immunisation with a human (hu) IFNα2b Kinoid (IFN-K) to break B cell tolerance to IFNα and to induce huIFNα-neutralising antibodies in mice immunotolerant to huIFNα2b was assessed.

Methods IFN-K was manufactured by crosslinking huIFNα2b to keyhole limpet haemocyanin (KLH). Transgenic mice expressing huIFNα2b received by intramuscular injection either saline or polymerised huIFNα2b as controls, or IFN-K, emulsified in ISA51vg adjuvant.

Results All of the huIFNα2b-expressing mice immunised with IFN-K generated neutralising antibodies against huIFNα2b. In addition, these antibodies neutralised all 13 subtypes of huIFNα. They also neutralised IFNα activity in sera collected from 10 different patients with active SLE. However, the antibodies did not bind to huIFNγ or huIFNβ. Finally, cellular activation assays showed that immunisation with IFN-K did not induce memory T cells reactive to native huIFNα2b, whereas it did induce memory cells reactive to KLH.

Conclusion These results show that active immunisation with IFN-K induces polyclonal antibodies that neutralise all subtypes of huIFNα as well as IFNα in sera from patients with SLE by breaking humoral but not cellular tolerance to IFNα. This suggests that immunisation with IFN-K is a promising new therapeutic strategy for the treatment of SLE.

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Footnotes

  • Funding Financial support was provided by Neovacs SA, Paris, France.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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