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162 Active Anti-IFN α Immunotherapy Applied to Chronic Viral and Autoimmune Diseases

Bizzini, Bernard1; Lebuanec, Hélène2; Gougeon, Marie-Lise2; Mathian, Alexis3; Amoura, Zahir3; Gallo, Robert C4; Zagury, Daniel1

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 68
doi: 10.1097/01.qai.0000397348.92555.b8
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1Neovacs 3/5 Impasse Reille Paris France; 2Institut Pasteur, Paris; 3CHU Pitié-Salpêtrière, Paris; and 4Institut of Human Virology, University of Maryland, Baltimore MD

IFN α has been involved in immunosuppression as a master regulatory transcript triggering particularly production of the anti-inflammatory cytokine Il 10. In chronic viral diseases including AIDS and in autoimmune diseases including Systemic Lupus Erythematosus, IFN α is abnormally overproduced.

HIV 1-infected individuals have been subjected to IFN α-Kinoid immunotherapy in a randomized placebo-controlled phase I/II trial (EURIS trial). In patients who developed anti-IFN α antibodies no HIV-related symptoms were observed and their CD4 cell count was stabilized over the 18-month follow-up period. IFN α-Kinoid proved to be both safe and immunogenic and efficient (1).

IFN α-Kinoid was also experimentally assessed in a murine SLE model expressing IFN α conveyed by an IFN α-Adv. Whereas control mice treated with the adjuvant (KLH) or PBS died, IFN α-Kinoid-vaccinated mice in which anti-IFN α Abs were elicited survived over the experimental follow up period without developing lupus symptoms (2). These clinical and experimental studies stress the safety, immunogenicity and proof of concept of IFN α-Kinoid immunotherapy.

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References

1. Gringeri A, et al. Active anti-interferon-alpha immunization: a European-Israeli, randomized, double-blind, placebo-controlled clinical trial in 242 HIV-1–infected patients (the EURIS study). J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20:358-70.
2. Zagury D, et al. IFNalpha kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine model. Proc Natl Acad Sci USA. 2009;106:5294-9.
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