title: Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine.
abstract: Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV.
  
  
  
  Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: Aitor
authors.initials: A
authors.lastname: Nogales
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Rodriguez
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chauché
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology and Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Reilly
authors.affiliation: David H. Smith Center for Vaccine Biology and Immunology and Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: David J
authors.identifier: http://orcid.org/0000-0002-9435-8673
authors.initials: DJ
authors.lastname: Topham
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
authors.forename: Pablo R
authors.identifier: http://orcid.org/0000-0002-4352-394X
authors.initials: PR
authors.lastname: Murcia
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Colin R
authors.identifier: http://orcid.org/0000-0002-1836-6655
authors.initials: CR
authors.lastname: Parrish
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA luis_martinez@urmc.rochester.edu.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Sobrido
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions; D004283:Dog Diseases / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D007114:Immunization; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053123:Influenza A Virus, H3N8 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000662:veterinary*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated
keywords: influenza; influenza vaccines