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2011-09-14Zeitschriftenartikel DOI: 10.1093/infdis/jir613
Influenza B Virus With Modified Hemagglutinin Cleavage Site as a Novel Attenuated Live Vaccine
dc.contributor.authorStech, Jürgen
dc.contributor.authorGarn, Holger
dc.contributor.authorHerwig, Astrid
dc.contributor.authorStech, Olga
dc.contributor.authorDauber, Bianca
dc.contributor.authorWolff, Thorsten
dc.contributor.authorMettenleiter, Thomas C.
dc.contributor.authorKlenk, Hans-Dieter
dc.date.accessioned2018-05-07T15:57:45Z
dc.date.available2018-05-07T15:57:45Z
dc.date.created2012-10-02
dc.date.issued2011-09-14none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/regi1QuhhFs/PDF/234KNNat9yV3U.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1319
dc.description.abstractBackground: Both pandemic and interpandemic influenza is associated with high morbidity and mortality worldwide. Seasonal epidemics are caused by both influenza A and B virus strains that cocirculate with varying predominance and may give rise to severe illness equally. According to World Health Organization recommendations, current annual vaccines are composed of 2 type A and 1 type B virus-specific component. Methods: As a novel attenuated live vaccine against influenza B virus, we generated a hemagglutinin cleavage site mutant of strain B/Lee/40 by replacing the common monobasic cleavage site recognized by trypsinlike proteases with an elastase-sensitive site, and we investigated the in vitro properties, attenuation, humoral responses, and efficacy in mice. Results. This mutant virus replicated in cell culture equally well as the wild type but in a strictly elastase-dependent manner. In contrast to the mouse-pathogenic parental virus, the cleavage site mutant was fully attenuated in mice and not detectable in their lungs. After 1 intranasal immunization, the animals survived lethal challenge with wild-type virus without weight loss or any other signs of disease. Furthermore, no challenge virus could be reisolated from the lungs of vaccinated mice. Conclusions: These findings demonstrate that proteolytic activation mutants can serve as live vaccine against influenza B virus.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectAnimalseng
dc.subjectFemaleeng
dc.subjectInfluenza B virus/geneticseng
dc.subjectMiceeng
dc.subjectMutationeng
dc.subjectMice Inbred BALB Ceng
dc.subjectAntibodies Viral/bloodeng
dc.subjectInfluenza Vaccines/immunologyeng
dc.subjectVaccines Synthetic/geneticseng
dc.subjectVaccines Synthetic/immunologyeng
dc.subjectHemagglutination Viral/geneticseng
dc.subjectInfluenza B virus/chemistryeng
dc.subjectInfluenza B virus/immunologyeng
dc.subjectInfluenza Vaccines/geneticseng
dc.subjectVaccines Attenuated/geneticseng
dc.subjectVaccines Attenuated/immunologyeng
dc.subject.ddc610 Medizin
dc.titleInfluenza B Virus With Modified Hemagglutinin Cleavage Site as a Novel Attenuated Live Vaccine
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10027370
dc.identifier.doi10.1093/infdis/jir613
dc.identifier.doihttp://dx.doi.org/10.25646/1244
local.edoc.container-titleJournal of Infectious Diseases
local.edoc.container-textJürgen Stech, Holger Garn, Astrid Herwig, Olga Stech, Bianca Dauber, Thorsten Wolff, Thomas C. Mettenleiter and Hans-Dieter Klenk. Influenza B Virus With Modified Hemagglutinin Cleavage Site as a Novel Attenuated Live Vaccine (2011) Journal of Infectious Diseases, 204 (10), pp. 1483-1490.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://jid.oxfordjournals.org/content/early/2011/09/13/infdis.jir613
local.edoc.container-publisher-nameOxford University Press
local.edoc.container-volume204
local.edoc.container-issue10
local.edoc.container-year2011

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