Canine influenza viruses with modified NS1 proteins for the development of live-attenuated vaccines

- We have generated by reverse genetics H3N8 CIVs containing truncated or a deleted NS1 protein.
- NS1 mutant H3N8 CIVs replicated efficiently in MDCK cells, important for vaccine production.
- H3N8 CIV with mutated NS1 are attenuated in vivo (mice) or ex vivo (canine tracheal explants).
- NS1 mutant viruses confer complete protection against challenge with WT H3N8 CIV.
- This is the first description of a LAIV for the prevention and control of H3N8 CIV in dogs.

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.