title: Nonreplicating vaccinia virus vectors expressing the H5 influenza virus hemagglutinin produced in modified Vero cells induce robust protection.
abstract: The timely development of safe and effective vaccines against avian influenza virus of the H5N1 subtype will be of the utmost importance in the event of a pandemic. Our aim was first to develop a safe live vaccine which induces both humoral and cell-mediated immune responses against human H5N1 influenza viruses and second, since the supply of embryonated eggs for traditional influenza vaccine production may be endangered in a pandemic, an egg-independent production procedure based on a permanent cell line. In the present article, the generation of a complementing Vero cell line suitable for the production of safe poxviral vaccines is described. This cell line was used to produce a replication-deficient vaccinia virus vector H5N1 live vaccine, dVV-HA5, expressing the hemagglutinin of a virulent clade 1 H5N1 strain. This experimental vaccine was compared with a formalin-inactivated whole-virus vaccine based on the same clade and with different replicating poxvirus-vectored vaccines. Mice were immunized to assess protective immunity after high-dose challenge with the highly virulent A/Vietnam/1203/2004(H5N1) strain. A single dose of the defective live vaccine induced complete protection from lethal homologous virus challenge and also full cross-protection against clade 0 and 2 challenge viruses. Neutralizing antibody levels were comparable to those induced by the inactivated vaccine. Unlike the whole-virus vaccine, the dVV-HA5 vaccine induced substantial amounts of gamma interferon-secreting CD8 T cells. Thus, the nonreplicating recombinant vaccinia virus vectors are promising vaccine candidates that induce a broad immune response and can be produced in an egg-independent and adjuvant-independent manner in a proven vector system.
authors.affiliation: Baxter Bioscience, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Mayrhofer
authors.forename: Sogue
authors.initials: S
authors.lastname: Coulibaly
authors.forename: Annett
authors.initials: A
authors.lastname: Hessel
authors.forename: Georg W
authors.initials: GW
authors.lastname: Holzer
authors.forename: Michael
authors.initials: M
authors.lastname: Schwendinger
authors.forename: Peter
authors.initials: P
authors.lastname: Brühl
authors.forename: Marijan
authors.initials: M
authors.lastname: Gerencer
authors.forename: Brian A
authors.initials: BA
authors.lastname: Crowe
authors.forename: Shen
authors.initials: S
authors.lastname: Shuo
authors.forename: Wanjing
authors.initials: W
authors.lastname: Hong
authors.forename: Yee Joo
authors.initials: YJ
authors.lastname: Tan
authors.forename: Barbara
authors.initials: B
authors.lastname: Dietrich
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sabarth
authors.forename: Helga
authors.initials: H
authors.lastname: Savidis-Dacho
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.forename: Falko G
authors.initials: FG
authors.lastname: Falkner
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops; D003673:Defective Viruses / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014616:Vaccinia virus / Q000235:genetics; D014709:Vero Cells; D014776:Virus Cultivation
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C483468:hemagglutinin, human influenza A virus; D007371:Interferon-gamma