An inactivated influenza D virus vaccine partially protects cattle from respiratory disease caused by homologous challenge

Authors: HAUSE, BEN - Kansas State University; HUNTIMER, LUCAS - Elanco Animal Health, Inc; Falkenberg, Shollie; HENNINGSON, JAMIE - Kansas State University; LECHTENBERG, KELLY - Desiderio Finamore Veterinary Research Institute (FEPAGRO); HALBUR, TOM - Midwest Veterinary Services

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/19/2016
Publication Date: 12/24/2016
Publication URL: http://handle.nal.usda.gov/10113/5695427
Citation: Hause, B.M., Huntimer, L., Falkenberg, S.M., Henningson, J., Lechtenberg, K., Halbur, T. 2016. An inactivated influenza D virus vaccine partially protects cattle from respiratory disease caused by homologous challenge. Veterinary Microbiology. 199(2017):47-53.

Interpretive Summary: Bovine respiratory disease (BRD) is the most economically important disease affecting the cattle industry and has a complex etiology including pathogen, environment and host factors. A primary viral insult is thought to predispose animals to secondary bacterial pneumonia which can lead to high morbidity, mortality and treatment costs. Influenza D virus (IDV) has recently been shown to be in diagnostic samples from cattle in the US and implicated to be an etiological viral agent associated with the BRD complex. Despite longstanding widespread use of multivalent viral vaccines, the incidence of BRD has been increasing for decades. While, it is unknown the continued increase in the incidence of BRD has been hypothesized to be due to emerging pathogens, such as IDV, that are not contained in the current viral vaccines. The data from this study demonstrated that IDV can cause mild respiratory disease characterized by rhinitis and tracheitis and readily transmits to contact animals. Importantly, it was demonstrated that the efficacy of an inactivated IDV vaccine could significantly reduce IDV titers in nasal and tracheal swabs and bronchoalveolar lavage fluids as well as reduce the number of animals positive for antigen in nasal and tracheal tissue. These results may translate to improved control strategies for BRD, by better understanding the role IDV plays in the etiology of the BRD complex as well as methods from protection of emerging viral pathogens.

Technical Abstract: Originally isolated from swine, the proposed influenza D virus has since been shown to be common in cattle. Inoculation of IDV to naïve calves resulted in mild respiratory disease histologically characterized by tracheitis. As several studies have associated the presence of IDV with acute bovine respiratory disease (BRD), we sought to investigate the efficacy of an inactivated IDV vaccine. Vaccinated calves seroconverted with hemagglutination inhibition titers 137-169 following two doses. Groups challenged with a homologous virus exhibited signs of mild respiratory disease from day 4-10 post challenge which was significantly different than negative controls at day 9 post challenge. Peak viral shedding of approximately 5 TCID50/mL was measured in nasal and tracheal swabs and bronchoalveolar lavage fluids 4-6 days post challenge which was significantly (P<0.05) decreased 1.0-1.6 TCID50/mL, 3.6 TCID50/mL and 3.8 TCID50/mL, respectively, in the aforementioned samples collected from vaccinated animals. Viral antigen was detected in the respiratory epithelium of the nasal turbinates and trachea by immunohistochemistry from all unvaccinated calves but in significantly fewer vaccinates. Inflammation characterized by neutrophils was observed in the nasal turbinate and trachea but not appreciably in lungs. IDV transmitted to all calves exposed via direct contact and displayed similar replication and shedding. Together these results support an etiologic role for IDV in BRD and demonstrate that partial protection is afforded by an inactivated vaccine.