IFNalpha kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine model.

Abstract:

:A major involvement of IFNalpha in the etiopathogenesis of systemic lupus erythematosus has been suggested by clinical observations, including the increase of serum levels of this cytokine in patients with active disease. Supporting this hypothesis, we have shown that expression of IFNalpha from a recombinant adenovirus (IFNalpha Adv) precipitates lupus manifestations in genetically susceptible New Zealand Black (NZB) x New Zealand White (NZW)F(1) mice (NZB/W) but not in BALB/c mice. In the present investigation, we have prepared an IFNalpha immunogen, termed IFNalpha kinoid, which, appropriately adjuvanted, induces transient neutralizing antibodies (Abs) but no cellular immune response to the cytokine and without apparent side effects. Using this preparation, we also showed that, in kinoid-vaccinated NZB/W mice, lupus manifestations, including proteinuria, histological renal lesions, and death triggered by IFNalpha Adv challenge were delayed/prevented as long as an effective threshold of anti-IFNalpha inhibitory capacity was present in the serum.

authors

Zagury D,Le Buanec H,Mathian A,Larcier P,Burnett R,Amoura Z,Emilie D,Peltre G,Bensussan A,Bizzini B,Gallo RC,Koutouzov S

doi

10.1073/pnas.0900615106

subject

Has Abstract

pub_date

2009-03-31 00:00:00

pages

5294-9

issue

13

eissn

0027-8424

issn

1091-6490

pii

0900615106

journal_volume

106

pub_type

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