title: Development of eczema vaccinatum in atopic mouse models and efficacy of MVA vaccination against lethal poxviral infection.
abstract: Smallpox vaccine based on live, replicating vaccinia virus (VACV) is associated with several potentially serious and deadly complications. Consequently, a new generation of vaccine based on non-replicating Modified vaccinia virus Ankara (MVA) has been under clinical development. MVA seems to induce good immune responses in blood tests, but it is impossible to test its efficacy in vivo in human. One of the serious complications of the replicating vaccine is eczema vaccinatum (EV) occurring in individuals with atopic dermatitis (AD), thus excluding them from all preventive vaccination schemes. In this study, we first characterized and compared development of eczema vaccinatum in different mouse strains. Nc/Nga, Balb/c and C57Bl/6J mice were epicutaneously sensitized with ovalbumin (OVA) or saline control to induce signs of atopic dermatitis and subsequently trans-dermally (t.d.) immunized with VACV strain Western Reserve (WR). Large primary lesions occurred in both mock- and OVA-sensitized Nc/Nga mice, while they remained small in Balb/c and C57Bl/6J mice. Satellite lesions developed in both mock- and OVA-sensitized Nc/Nga and in OVA-sensitized Balb/c mice with the rate 40-50%. Presence of mastocytes and eosinophils was the highest in Nc/Nga mice. Consequently, we have chosen Nc/Nga mice as a model of AD/EV and tested efficacy of MVA and Dryvax vaccinations against a lethal intra-nasal (i.n.) challenge with WR, the surrogate of smallpox. Inoculation of MVA intra-muscularly (i.m.) or t.d. resulted in no lesions, while inoculation of Dryvax t.d. yielded large primary and many satellite lesions similar to WR. Eighty three and 92% of mice vaccinated with a single dose of MVA i.m. or t.d., respectively, survived a lethal i.n. challenge with WR without any serious illness, while all Dryvax-vaccinated animals survived. This is the first formal prove of protective immunity against a lethal poxvirus challenge induced by vaccination with MVA in an atopic organism.
authors.affiliation: Department of Immunology and Microbiology, 1st Medical Faculty, Charles University, Studnickova 7, 128 00, Prague 2, Czech Republic.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Knitlova
authors.affiliation: Department of Immunology and Microbiology, 1st Medical Faculty, Charles University, Studnickova 7, 128 00, Prague 2, Czech Republic.
authors.forename: Vera
authors.initials: V
authors.lastname: Hajkova
authors.affiliation: Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Videnska 9, 140 21, Prague 4, Czech Republic.
authors.forename: Ludek
authors.initials: L
authors.lastname: Voska
authors.affiliation: Department of Immunology and Microbiology, 1st Medical Faculty, Charles University, Studnickova 7, 128 00, Prague 2, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Elsterova
authors.affiliation: Department of Immunology and Microbiology, 1st Medical Faculty, Charles University, Studnickova 7, 128 00, Prague 2, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Obrova
authors.affiliation: Department of Immunology and Microbiology, 1st Medical Faculty, Charles University, Studnickova 7, 128 00, Prague 2, Czech Republic.
authors.forename: Zora
authors.initials: Z
authors.lastname: Melkova
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007617:Kaposi Varicelliform Eruption / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D011213:Poxviridae Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D012867:Skin / Q000473:pathology; D012900:Smallpox Vaccine / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D012900:Smallpox Vaccine; D007073:Immunoglobulin E