First Report of a Live Attenuated Canine Influenza Virus for Potential Vaccine Development

Researchers are a step closer to a new vaccine against canine influenza, according to a report recently published in Virology. The influenza vaccines currently available for dogs in the United States are inactivated (killed) vaccines. In this study, investigators generated a recombinant live attenuated influenza virus and showed that it could protect against canine H3N8 influenza virus infection.

Canine influenza is highly contagious among dogs, causing illness ranging from a mild cough and nasal discharge to severe pneumonia. Some strains of influenza virus have spread between dogs and other species, raising the possibility that reassortment of canine and human influenza virus strains could create a public health concern. (There is no evidence so far that dog-to-human transmission has occurred.) Vaccination against canine influenza is one tool that can be used to control the spread of the disease.

Inactivated vaccines are safe because they cannot cause disease, but they provoke a weaker immune response than do live attenuated vaccines and usually require a booster vaccination. Inactivated vaccines are available for both strains of canine influenza virus, H3N8 and H3N2, that are currently circulating in the United States. The H3N8 vaccine for dogs was approved in 2009, and the H3N2 vaccine became available in 2015. According to the American Veterinary Medical Association, the H3N8 vaccine does not necessarily prevent infection but may reduce the severity of disease and the amount of virus shed into the environment.

Live attenuated vaccines, which are created by modifying pathogens in the laboratory, typically produce a stronger immune response than do inactivated vaccines and can also induce cell-mediated immunity. Some can be given intranasally rather than by intramuscular injection. However, because they contain live pathogens, they could potentially cause disease if the organism in the vaccine reverts to a virulent form or if the recipient is immunocompromised.

The authors of the study published in Virology used reverse genetics to truncate or delete the NS1 protein of the canine H3N8 virus. NS1 counteracts the host interferon response, and live attenuated vaccines against other influenza virus strains have been created by modifying this protein.

The results, say the authors, suggest that their NS1-modified virus could be used as a live attenuated vaccine against canine H3N8 influenza. Their findings include the following:

• The modified virus was able to replicate in Madin-Darby canine kidney (MDCK) cells. This is important because influenza vaccines are often produced by culturing virus in mammalian cells such as MDCK rather than in eggs.
• The modified virus was attenuated in vivo. Although it replicated in the lungs of experimentally infected mice, it produced much lower virus titers than did the wild-type virus.
• The modified virus was also attenuated ex vivo, causing less severe changes in canine tracheal explants than were seen with wild-type virus.
• The modified virus conferred protection against influenza infection in vivo. The investigators inoculated mice with one dose of the modified virus (intranasally) or the commercially available inactivated canine H3N8 vaccine (intramuscularly) and then experimentally infected the mice with canine H3N8 influenza virus. Both vaccines induced antibody formation. The researchers found no virus replication in the lungs of mice inoculated with the NS1-truncated virus. In mice given the inactivated vaccine, however, virus titers were high on day 2 after infection and were cleared by day 4.

According to the authors, this is the first report of a live attenuated canine H3N8 virus generated by targeting the NS1 protein. They conclude that this modified virus has strong potential for use as a live attenuated vaccine against canine H3N8 influenza virus infection.

The study was supported by the University of Rochester, the Horserace Betting Levy Board, and the Medical Research Council of the United Kingdom.

Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.