Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Active Immunization with IFN Kinoid Induces Polyclonal Antibodies That Neutralize IFN From Systemic Lupus Erythematosus Patients
Mathian1, Alexis, Amoura1, Zahir, Adam2, Estelle, Colaone2, Fabien, Hoekman3, Marco F.M., Vandepapeliere2, Pierre, Haroche1, Julien
Pitié-Salpêtrière hospital, Paris, France
NEOVACS SA, Paris, France
Utrecht University, Utrecht, Netherlands
Department of Internal Medicine, Pitié-Salpêtrière Hospital, Paris, France
Department of Virology, Saint-Vincent de Paul Hospital, Paris, France
Passive administration of monoclonal antibodies (mAbs) has been shown to be effective for the treatment of autoimmune diseases such as rheumatoid arthritis, but its therapeutic use is limited by the immunogenicity of the antibodies. Additionally, several cytokines such as interferon-alpha (IFNa), the key cytokine implicated in systemic lupus erythematosus (SLE), have different subtypes, which make very difficult and unlikely their neutralization by a single mAb. The Kinoid® immunization process developed by Neovacs is a novel approach that targets cytokines by inducing natural polyclonal antibody response and circumvents the induction of the anti-mAbs response. Kinoids® are heterocomplexes made by conjugating the targeted cytokine to a carrier protein such as the keyhole limpet hemocyanin (KLH).
In the current study, FVB human IFNa2b transgenic mice were immunized with IFNa2b Kinoid (IFN-K) formulated in ISA51 adjuvant (SEPPIC). Control mice were immunized with inactivated IFNa2b emulsified in ISA51. This inactivated IFNa2b control was manufactured the same way as IFN-K but in absence of KLH.
Only mice immunized with IFN-K generated neutralizing antibodies against IFNa2b.Furthermore, these antibodies neutralized all the 13 human IFNa subtypes, as assessed by the compendial Madin Darby bovine kidney-vesicular stomatitis virus infection assay. When the assay was performed with sera from SLE patients as a source of IFNa, the protective IFNa activity was neutralized by these polyclonal antibodies. However, the antibodies induced by IFN-K immunization neutralize neither IFNb nor IFNg. In vitro stimulation with native human IFNa2b of splenocytes from IFN-K immunized mice did not induce a cellular response, whereas it did with IFN-K and KLH antigens.
Our study shows that in mice tolerant to human IFNa2b:
Active immunization with IFN-K induces polyclonal antibodies that specifically neutralize all subtypes of human IFNa,
Active immunization with IFN-K breaks B-cell but not T-cell tolerance to IFNa thus demonstrating the safety of the product,
Polyclonal antibodies produced by active immunization with IFN-K are able to neutralize human IFNa present in sera from SLE patients,
The IFNa2b-kinoid vaccine is a promising new therapeutic strategy for the treatment of SLE.
To cite this abstract, please use the following information:
Mathian, Alexis, Amoura, Zahir, Adam, Estelle, Colaone, Fabien, Hoekman, Marco F.M., Vandepapeliere, Pierre, et al; Active Immunization with IFN Kinoid Induces Polyclonal Antibodies That Neutralize IFN From Systemic Lupus Erythematosus Patients [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1050