title: Canine influenza viruses with modified NS1 proteins for the development of live-attenuated vaccines.
abstract: Canine Influenza Virus (CIV) H3N8 is the causative agent of canine influenza, a common and contagious respiratory disease of dogs. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV H3N8. However, live-attenuated influenza vaccines (LAIVs) are known to provide better immunogenicity and protection efficacy than IIVs. Influenza NS1 is a virulence factor that offers an attractive target for the preparation of attenuated viruses as LAIVs. Here we generated recombinant H3N8 CIVs containing truncated or a deleted NS1 protein to test their potential as LAIVs. All recombinant viruses were attenuated in mice and showed reduced replication in cultured canine tracheal explants, but were able to confer complete protection against challenge with wild-type CIV H3N8 after a single intranasal immunization. Immunogenicity and protection efficacy was better than that observed with an IIV. This is the first description of a LAIV for the prevention of H3N8 CIV in dogs.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
authors.forename: Aitor
authors.initials: A
authors.lastname: Nogales
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chauché
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA; Center for Vaccine Biology and Immunology (CVBI), University of Rochester, Rochester, NY, USA.
authors.forename: Marta L
authors.initials: ML
authors.lastname: DeDiego
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Murcia
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Parrish
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA. Electronic address: luis_martinez@urmc.rochester.edu.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Sobrido
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D004283:Dog Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D004285:Dogs; D005260:Female; D006801:Humans; D053123:Influenza A Virus, H3N8 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; C085820:INS1 protein, influenza virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins
keywords: Canine influenza virus; Canine tracheal explant; Inactivated influenza vaccines; Influenza A virus; Live-attenuated influenza vaccines; NS1 deficient influenza viruses; Non-structural protein 1; Reverse genetics