IFNalpha kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine model.
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.
Zagury
Daniel
D
Neovacs SA, 3-5 Impasse Reille, 75014 Paris, France. dzagury@neovacs.com
Le Buanec
Hélène
H
Mathian
Alexis
A
Larcier
Patrick
P
Burnett
Roger
R
Amoura
Zahir
Z
Emilie
Dominique
D
Peltre
Gabriel
G
Bensussan
Armand
A
Bizzini
Bernard
B
Gallo
Robert C
RC
Koutouzov
Sophie
S
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*
D000906:Antibodies; D016898:Interferon-alpha; D014612:Vaccines