INDUCTION, TREATMENT AND PREVENTION OF ECZEMA VACCINATUM IN POXVIRUS INFECTED MOUSE MODEL OF ATOPIC DERMATITIS

Eczema vaccinatum (EV) is a severe and occasionally lethal complication, of smallpox vaccine, characterized by systemic viral dissemination outside of the initial inoculation site of the vaccine. A major risk factor for EV is a background of atopic dermatitis (AD), a chronic, predominantly affecting children, relapsing, skin disease manifested by dry and inflamed skin, itchy rash, TH2 biased immune response and hypersensitivity to various antigens.

We established two mouse models for AD, by repeated application of 2-4-dinitroflurobenze (DNFB) on the skin of SKH-1 (hairless) and Nc/Nga mice. This provoked persistent severe dermatitis, characterized by dry and inflamed skin with barrier dysfunction, epidermal hyperplasia and significant elevation in serum IgE levels.

Next, we established an EV model by infecting the DNFB mice with ectromelia virus (ECTV), a natural mouse pathogen, closely related to smallpox vaccine. Similarly to huamans, EV-mice displayed enlarged and disseminated skin lesions, which correlated with elevated viral load in the skin, and internal organs. Cidofovir (CDV) and antiviral antibodies treatment of eczematous mice, starting three days post infection (p.i.) prevented mortality and morbidity. Moreover, human equivalent, high-dose, CDV treatment prevented mortality even when started 8 days p.i., already at the eczematous stage. Finally, we demonstrate that MVA vaccination of AD mice provoked immune response despite the severe AD background and protected from lethal ECTV challenge even if vaccination was conducted one day p.i., suggesting that MVA vaccination, and even prophylactic vaccination would be efficacious is preventing EV and in protecting even severe AD patients against smallpox.