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Statements

Subject Item
n2:RIV%2F00216208%3A11110%2F14%3A10287221%21RIV15-MSM-11110___
rdf:type
n3:Vysledek skos:Concept
rdfs:seeAlso
http://dx.doi.org/10.1371/journal.pone.0114374
dcterms:description
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 C57BI/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 C57BI/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. 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 C57BI/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 C57BI/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.
dcterms:title
Development of Eczema Vaccinatum in Atopic Mouse Models and Efficacy of MVA Vaccination against Lethal Poxviral Infection Development of Eczema Vaccinatum in Atopic Mouse Models and Efficacy of MVA Vaccination against Lethal Poxviral Infection
skos:prefLabel
Development of Eczema Vaccinatum in Atopic Mouse Models and Efficacy of MVA Vaccination against Lethal Poxviral Infection Development of Eczema Vaccinatum in Atopic Mouse Models and Efficacy of MVA Vaccination against Lethal Poxviral Infection
skos:notation
RIV/00216208:11110/14:10287221!RIV15-MSM-11110___
n5:aktivita
n15:S n15:P n15:I
n5:aktivity
I, P(ED1.1.00/02.0109), S
n5:cisloPeriodika
12
n5:dodaniDat
n7:2015
n5:domaciTvurceVysledku
n6:4928466 n6:2438747 n6:7628625 n6:2362902 n6:5089972
n5:druhVysledku
n16:J
n5:duvernostUdaju
n11:S
n5:entitaPredkladatele
n19:predkladatel
n5:idSjednocenehoVysledku
10982
n5:idVysledku
RIV/00216208:11110/14:10287221
n5:jazykVysledku
n20:eng
n5:klicovaSlova
dermatitis; skin-lesions; united-states; animal-models; protein-kinase; dendritic cells; nc/nga mice; virus ankara; immune-response; smallpox vaccine
n5:klicoveSlovo
n9:smallpox%20vaccine n9:dermatitis n9:skin-lesions n9:nc%2Fnga%20mice n9:animal-models n9:immune-response n9:virus%20ankara n9:protein-kinase n9:dendritic%20cells n9:united-states
n5:kodStatuVydavatele
US - Spojené státy americké
n5:kontrolniKodProRIV
[90B957E7E09B]
n5:nazevZdroje
PLoS ONE
n5:obor
n8:EE
n5:pocetDomacichTvurcuVysledku
5
n5:pocetTvurcuVysledku
6
n5:projekt
n17:ED1.1.00%2F02.0109
n5:rokUplatneniVysledku
n7:2014
n5:svazekPeriodika
9
n5:tvurceVysledku
Mělková, Zora Knitlová, Jarmila Hájková, Věra Obrová, Barbora Elsterová, Jana Voska, Ludek
n5:wos
000346907600050
s:issn
1932-6203
s:numberOfPages
24
n12:doi
10.1371/journal.pone.0114374
n13:organizacniJednotka
11110