title: Influenza B virus with modified hemagglutinin cleavage site as a novel attenuated live vaccine.
abstract: BACKGROUND
  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.
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald, Insel Riems, Germany. juergen.stech@fli.bund.de
authors.forename: Jürgen
authors.initials: J
authors.lastname: Stech
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.forename: Astrid
authors.initials: A
authors.lastname: Herwig
authors.forename: Olga
authors.initials: O
authors.lastname: Stech
authors.forename: Bianca
authors.initials: B
authors.lastname: Dauber
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wolff
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006387:Hemagglutination, Viral / Q000235:genetics; D009981:Influenza B virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic