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

A major involvement of IFNα 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 IFNα from a recombinant adenovirus (IFNα Adv) precipitates lupus manifestations in genetically susceptible New Zealand Black (NZB) × New Zealand White (NZW)F1mice (NZB/W) but not in BALB/c mice. In the present investigation, we have prepared an IFNα immunogen, termed IFNα 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 IFNα Adv challenge were delayed/prevented as long as an effective threshold of anti-IFNα inhibitory capacity was present in the serum.