POX VIRUS INFECTION OF ALLERGEN SENSITIZED MICE INDUCES SEVER ECZEMA VACCINATUM WHICH IS EFFECTIVELY SUPPRESSED BY TREATMENT WITH ANTIVIRAL AND SPECIFIC ANTIBODY

Eczema vaccinatum (EV) is a severe and occasionally lethal complication, of live vaccinia virus immunization, which occurs in patient with atopic dermatitis (AD). AD is a relapsing skin disease of complex etiology which affect more than 15% of children in US population. It is characterized by dry and inflamed skin, itchy rash, TH2 biased immune response and hypersensitivity to various antigens.

The AD and EV models we present here, are the first to simulate the severity of the diseases in humans. Similarly to humans, the AD mice in our model, display persistent severe dermatitis, characterized by dry and inflamed skin, increase in TEWL, epidermal hyperplasia and significant elevation of serum IgE. By exposing AD mice to ectromelia virus, we generated for the first time EV mice that mimic the human disease better than known EV models. Similarly to humans, EV mice displayed enlarged and disseminated skin lesions, which correlated with elevated viral load. The severe EV mouse model and the use of hairless mice enabled us to examine possible therapeutics for EV. We demonstrate for the first time, successful protection of severely eczematic mice, using Cidofovir and antiviral antibodies, even when the treatment started at a late eczematous stage. Moreover, we are the first to demonstrate that MVA vaccination of severely dermatitic mice protects against lethal ectromelia challenge and that severe EV can be successfully treated post exposure with MVA. Moreover, we demonstrate that CD4⁺ T cells are crucial for protection from EV by MVA vaccination and that MVA vaccination of AD mice activates CD8⁺ T cells.