title: The potential of a protease activation mutant of a highly pathogenic avian influenza virus for a pandemic live vaccine.
abstract: The most effective countermeasure against a pandemic originating from a highly pathogenic avian influenza virus (HPAIV) is immunoprophylaxis of the human population. We present here a new approach for the development of a pandemic HPAIV live vaccine. Using reverse genetics, we replaced the polybasic hemagglutinin cleavage site of an H7N7 HPAIV with an elastase motif. This mutant was strictly elastase-dependent, grew equally well as the wild-type in cell culture and was attenuated in mice unlike the lethal wild-type. Immunization at 10(6)pfu dosage protected mice against disease and induced sterile immunity; vaccination with homosubtypic or heterosubtypic reassortants led to cross-protection. These observations demonstrate that a mutated hemagglutinin requiring elastase cleavage can serve as an attenuating component of a live vaccine against HPAIV.
authors.affiliation: Institut für Virologie, Fachbereich Medizin, Philipps-Universität Marburg, Germany. guelsah.gabriel@path.ox.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Gabriel
authors.forename: H
authors.initials: H
authors.lastname: Garn
authors.forename: M
authors.initials: M
authors.lastname: Wegmann
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: A
authors.initials: A
authors.lastname: Herwig
authors.forename: H-D
authors.initials: HD
authors.lastname: Klenk
authors.forename: J
authors.initials: J
authors.lastname: Stech
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D002460:Cell Line; D002522:Chlorocebus aethiops; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D053126:Influenza A Virus, H7N7 Subtype / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D010196:Pancreatic Elastase / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014709:Vero Cells
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D010196:Pancreatic Elastase