title: Potent vesicular stomatitis virus-based avian influenza vaccines provide long-term sterilizing immunity against heterologous challenge.
abstract: The emergence in 1997 and continuance today of a highly lethal H5N1 avian influenza virus (AIV) causing human disease has raised concern about an impending pandemic and the need for a vaccine to prepare for such an occurrence. We previously generated an efficacious vesicular stomatitis virus (VSV)-based AIV vaccine expressing H5 hemagglutinin (HA) from the fifth genomic position of VSV (J. A. Schwartz et al., Virology 366:166-173, 2007). Here we have generated and characterized VSV-based vaccines that express the A/Hong Kong/156/1997 (clade 0) H5 HA from the first position of the VSV genome. These vectors induce broadly cross-neutralizing antibodies against homologous and heterologous H5N1 viruses of different clades in mice. The vaccines provide complete protection against morbidity and mortality after heterologous challenge with clade 0 and clade 1 strains in animals even 1 year after vaccination. Postchallenge pulmonary virus loads show that these vectors provide sterilizing immunity. Therefore, VSV-based AIV vaccines are potent, broadly cross-protective pandemic vaccine candidates.
authors.affiliation: Department of Pathology, Yale University School of Medicine, 310 Cedar St., LH 315, New Haven, CT 06520, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Schwartz
authors.forename: Linda
authors.initials: L
authors.lastname: Buonocore
authors.forename: Amorsolo L
authors.initials: AL
authors.lastname: Suguitan
authors.forename: Alex
authors.initials: A
authors.lastname: Silaghi
authors.forename: Darwyn
authors.initials: D
authors.lastname: Kobasa
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D056738:Cross Protection; D005260:Female; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D016019:Survival Analysis; D013997:Time Factors; D018116:Vesiculovirus / Q000235:genetics*; D010948:Viral Plaque Assay
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C109963:hemagglutinin, avian influenza A virus