Longitudinal study of humoral immunity to bovine coronavirus, virus shedding, and treatment for bovine respiratory disease in pre-weaned beef calves

Authors: Workman, Aspen; Kuehn, Larry; McDaneld, Tara; Clawson, Michael - Mike; LOY, JOHN - University Of Nebraska

Submitted to: BioMed Central (BMC) Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2019
Publication Date: 5/22/2019
Citation: Workman, A.M., Kuehn, L.A., McDaneld, T.G., Clawson, M.L., Loy, J.D. 2019. Longitudinal study of humoral immunity to bovine coronavirus, virus shedding, and treatment for bovine respiratory disease in pre-weaned beef calves. BioMed Central (BMC) Veterinary Research. 15:161. https://doi.org/10.1186/s12917-019-1887-8.
DOI: https://doi.org/10.1186/s12917-019-1887-8

Interpretive Summary: Bovine respiratory disease (BRD) is the leading cause of illness and death for all production classes of cattle and calves in the United States. BRD is caused by complex interactions among the host, viruses, bacteria, stress and the environment. Bovine coronavirus (BCV) is a viral pathogen that has recently been described as being an important player in respiratory disease in weaned cattle entering the feedlot. Multiple studies have shown BCV can be isolated from the lungs of sick calves, and that cattle that enter the feedlot with high titers of anti-BCV antibodies are less likely to develop BRD than those with low antibody titers. In contrast, the relationship between anti-BCV antibody titers, BCV infection, and BRD in nursing beef calves has not been comprehensively evaluated. To address this important knowledge gap, we serially sampled calves from multiple research herds from birth to weaning to determine the whether shedding of BCV is associated with BRD and whether high levels of anti-BCV antibodies protect calves from BCV infection and disease. This study found that BCV was significantly associated with BRD cases; however, there was no correlation between antibody titers and virus infection or disease. Thus, high antibody titers did not appear to protect calves from disease. The aspects of the immune system (antibodies or cellular components) that are associated with protection from BCV infection and BRD are unknown and have hinderd the development of effective control strategies. This is significant, as there are currently no licensed BCV vaccines to aid in the prevention of BRD. This study represents a first step in understanding how host immunity relates to BCV infection and how BCV interacts with other pathogens to cause disease in nursing calves. This work has important implications for diagnostic labs, vaccine producers, and researchers investigating the contributions of BCV to BRD.

Technical Abstract: Background: Bovine coronavirus (BCV) is associated with respiratory infections in cattle of all ages; however, a temporal study to evaluate the effect of BCV immunity on virus shedding and bovine respiratory disease (BRD) incidence in pre-weaned beef calves has not been reported. Thus, we report here a prospective study in three herds of crossbred beef calves (n = 817) with endemic BCV. Serial blood samples for measurement of serum anti-BCV antibody titers and nasal swabs for detection of BCV and other common viral and bacterial BRD pathogens were collected from all calves or subsets of calves at predetermined times from birth through weaning. The calves were monitored for BRD and those that developed signs of respiratory disease were sampled for diagnostic testing. To discover additional risk factors that could have influenced BRD development, sequence analysis of the BCV strain(s) circulating in each herd, and the prevalence of common opportunistic bacterial pathogens in the upper respiratory tract of sick and apparently healthy cattle were also evaluated. Results: Two hundred forty-eight of the 817 study calves (30.4%) were treated for BRD prior to weaning; 246 of those were from a single herd involved in two outbreaks of BRD leading to mass treatment of all calves in that group. Molecular diagnostic testing found BCV and Histophilus somni in nasal swabs taken at the time of BRD treatment. Between herd analyses revealed anti-BCV serum antibody abundance did not associate with the incidence of BRD or BCV shedding, though these measurements may have been hindered by the long periods between sample collections. Analysis of the BCV spike gene hypervariable region revealed four polymorphisms in 15 isolates from the three herds, making strain variation unlikely to account for differences in treatment rates between herds. Persistent or recurrent shedding episodes of BCV occurred in some animals treated for BRD. Conclusion: Co-detection of BCV and H. somni at the time of the disease outbreak suggests that these pathogens contributed to disease pathogenesis. Developing appropriate control measures for respiratory BCV infections may help decrease the incidence of pre-weaning BRD. The role of antibodies in protection must still be further defined.