title: Post-exposure treatment with whole inactivated H5N1 avian influenza virus protects against lethal homologous virus infection in mice.
abstract: Concerns with H5N1 influenza viruses include their prevalence in wild and domestic poultry, high mortality rate (~60%) in humans with some strains, lack of pre-existing immunity in humans, and the possibility that these viruses acquire mutations that enable efficient transmission between humans. H5 subtype viruses of Eurasian origin have recently appeared in wild and domestic bird populations in North America, and have led to the generation of new virus strains that are highly pathogenic in poultry. These new H5 HA containing viruses with their ability to evolve rapidly represent an unknown threat to humans in contact with infected poultry, and vaccination with an off-the-shelf vaccine may be impractical to provide protection to at-risk individuals. Instead, we have evaluated the efficacy of a formalin-inactivated vaccine, which could be derived directly from a circulating virus, to provide post-exposure protection. This strategy was evaluated using a prototypic highly pathogenic avian H5N1 strain, A/Vietnam/1203/2004, and demonstrated rapid induction of adaptive immune responses providing protection in a mammalian model of lethal infection. Additionally, this post-exposure vaccine was highly efficacious when administered 24 hours after exposure. This study offers a platform for developing effective post-exposure vaccines for treatment of highly virulent influenza infections.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.|High Containment Respiratory Viruses, Special Pathogens Program, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Mable
authors.initials: M
authors.lastname: Hagan
authors.affiliation: High Containment Respiratory Viruses, Special Pathogens Program, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Charlene
authors.initials: C
authors.lastname: Ranadheera
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.|High Containment Respiratory Viruses, Special Pathogens Program, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Audet
authors.affiliation: Département des Technologies de laboratoire, Cégep de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Morin
authors.affiliation: High Containment Respiratory Viruses, Special Pathogens Program, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Anders
authors.initials: A
authors.lastname: Leung
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.|High Containment Respiratory Viruses, Special Pathogens Program, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Darwyn
authors.initials: D
authors.lastname: Kobasa
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D004285:Dogs; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated