Are We Vaccinating for the Right BRD Viruses?

Background

Recently-weaned auction-market sourced feedlot calves are susceptible to respiratory viral infections. Infected calves can shed viruses, infect pen-mates, increase the risk of bacterial infection and the need for antimicrobial treatment of bovine respiratory disease (BRD).

Commercial BRD vaccines typically target BoHV-1, BPIV-3, BRSV, BVDV1 and BVDV2 viruses. Calves that have been successfully vaccinated (prime & boost) against these viruses at the farm of origin should be less likely to become infected and shed virus when they arrive at the feedlot. However, commercial respiratory vaccines do not protect against other viruses that have also been associated with BRD. These include bovine coronavirus (BCoV), influenza D virus (IDV) and bovine rhinitis B virus (BRBV).

Many diagnostic laboratories use PCR-based tests that can only detect specific viruses and bacteria it is told to look for. In contrast, new metagenomic sequencing-based tests have the potential to detect all microbes (both known and unknown) in the sample. This research used metagenomic sequencing to study the diversity, prevalence and dynamics of respiratory viruses early in the feeding period, with the goal of identifying vaccination gaps and determine how these viruses may predispose feedlot calves to subsequent clinical BRD.

Objectives

• Advance and refine a protocol for metagenomic sequence & bioinformatic analyses for the detection of respiratory viruses potentially associated with bovine respiratory disease (BRD) in feedlot cattle
• Describe respiratory viruses associated with BRD in feedlot calves at arrival processing to identify possible vaccine gaps at the cow-calf level. (Do we need enhanced uptake of vaccination or new viral respiratory vaccines for preweaned calves?)
• Determine if respiratory viruses detected early in the feeding period can predict the future risk of a feedlot calf developing clinical BRD

What they Did

A commercial feedlot study used a refined metagenomic sequencing protocol optimized for virus detection and an automated bioinformatics platform to simultaneously detect respiratory viruses, bacterial BRD pathogens and antimicrobial resistance genes (ARGs) in 760 short nasal samples (NS) collected from fall placed calves and yearlings in 19 commercial feedlots at two time points early in the feeding period. A commercial qPCR test was also used to detect specific viruses. They assessed the performance (sensitivity and specificity) of metagenomic sequencing and qPCR to detect viruses commonly associated with BRD. Potential vaccine gaps in cow-calf herds were identified based on the detection of respiratory viruses at arrival processing.

High Sensitivity means that infected (positive) animals are correctly identified therefore there are few false positives

High Specificity means that uninfected (positive) animals are correctly identified thereofre there are few false negatives

A research feedlot study used metagenomic sequencing to detect BRD viruses in deep nasopharyngeal samples (DNPS) collected from 729 fall-placed calves at three time points early in the feeding period. They evaluated whether specific viruses detected at arrival processing or at 13 days on feed (DOF) were associated with future risk of BRD treatment. They followed individual calves over time to determine whether the same viruses were present at arrival, at 13 DOF, and when treated for BRD. They also examined whether specific viruses were more common in calves treated for BRD compared to health pen mates (case-control study).

What They Learned

Twenty-one viruses were detected in the commercial feedlot study. Lesser-known viruses that have been linked to BRD but that are not found in commercial BRD vaccines (e.g., BCoV, IDV and BRBV) were detected much more often and at higher levels than for most respiratory viruses found in commercial vaccines (BoHv1, BPIV3, BVDV1 and BVDV2). BRSV was the exception – it was commonly detected in cattle even though it is included in commercial vaccines. Regardless of sample type (NS or DNPS) and feedlot setting (large pen commercial or research), BCoV was the most frequently detected respiratory virus in feedlot calves early in the feeding period. The sensitivity of both metagenomic sequencing and qPCR was low for detection of most viruses associated with BRD, however the specificity was consistently high.

BRD bacteria (including M. haemolytica, H. somni, P. multocida, M. bovis, B. trehalosi and others)were also detected in samples prepared with a protocol optimized for virus detection. M. haemolytica was the most frequently detected respiratory bacteria and its prevalence in calves increased significantly two weeks after arrival. 33 ARGs were also detected, but only in 6% of samples. The two most common ARGs were associated with antimicrobial classes that are not used in the Canadian cattle industry.

The future risk of a feedlot calf developing BRD could not be predicted based on the detection of respiratory viruses on arrival or two weeks later. However, BCoV was found much more frequently in calves treated for BRD compared to healthy penmates sampled at the same time.

What It Means

Metagenomic sequencing and bioinformatics protocols offer diagnostic laboratories a feasible, faster, and less expensive alternative to detect both respiratory viruses and bacterial BRD pathogens compared to traditional tests. However, this approach is currently not ideal for detecting the antimicrobial resistance genes that are most relevant for the cattle industry.

The research greatly improved our understanding of the diversity, prevalence and dynamics of respiratory viruses and bacteria early in the feeding period. The BRSV component of commercial viral vaccines likely needs to be updated to protect against current field strains. If the association between BCoV and BRD is confirmed, viral respiratory disease vaccines may also need to add BCoV.