title: 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.affiliation: Neovacs SA, 3-5 Impasse Reille, 75014 Paris, France. dzagury@neovacs.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Zagury
authors.forename: Hélène
authors.initials: H
authors.lastname: Le Buanec
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Patrick
authors.initials: P
authors.lastname: Larcier
authors.forename: Roger
authors.initials: R
authors.lastname: Burnett
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
authors.forename: Gabriel
authors.initials: G
authors.lastname: Peltre
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Bernard
authors.initials: B
authors.lastname: Bizzini
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gallo
authors.forename: Sophie
authors.initials: S
authors.lastname: Koutouzov
mesh_terms: D000818:Animals; D000906:Antibodies; D000917:Antibody Formation; D003643:Death; D004195:Disease Models, Animal; D016898:Interferon-alpha / Q000276:immunology*; D007674:Kidney Diseases; D008180:Lupus Erythematosus, Systemic / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D011507:Proteinuria; D013045:Species Specificity; D016896:Treatment Outcome; D014612:Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D016898:Interferon-alpha; D014612:Vaccines