Comparison of pre-weaning bovine respiratory disease treatment rates between non-vaccinated control and variably primed and boosted beef calves receiving commercially available bovine coronavirus vaccines

Abstract

Objective

The primary objective was to determine effectiveness of bovine coronavirus (BCoV) vaccination of neonatal calves in the face of natural respiratory infection in a commercial herd.

Animals

At a privately owned ranch in north-central Alberta with a history of bovine respiratory disease (BRD), beef calves of mixed sex and breed were randomized into a clinical vaccine trial.

Procedure

At birth, 447 calves were enrolled into the vaccine (VAC) group and administered an intranasal dose of BCoV vaccine, and 439 calves were enrolled as controls (CON). Most VAC calves (n = 389) also received an intramuscular dose of BCoV vaccine at an average of 49 d (SD: 7 d). Treatment for BRD and total mortality were recorded until pasture turnout. Weaning weights were collected at the end of the grazing season. A partial budget comparison included costs of vaccination and treatment, as well as potential revenues using weaning weights and regional sale summaries.

Results

Calves in the CON group were more likely than VAC calves to be treated before turnout vaccination (OR: 1.50; P = 0.048) and calves born in the 2nd cycle were more likely than 3rd-cycle calves to be treated for BRD (OR: 2.90; P = 0.01). The odds of mortality for CON calves born in the 2nd cycle were higher (OR: 4.8; P = 0.001) than for VAC calves. Weaning weights were higher for VAC calves (P = 0.04) and, despite increased costs due to vaccination, revenue for VAC calves was an average of $10.50/head higher.

Conclusion

Vaccination of neonatal calves with BCoV vaccine reduced the frequency of BRD treatment and total mortality and improved weaning weights and revenue potential in this herd.

Clinical relevance

Vaccination with commercial BCoV vaccines could be an important tool to control neonatal BRD, particularly in herds with a history of disease not responsive to other BRD vaccines.

INTRODUCTION

Bovine respiratory disease (BRD) involves numerous coincident host, environmental, and pathogen cofactors that allow the upper and/or lower respiratory tracts to become coinfected by various bacterial and viral pathogens (1–4). Primary viral infection of the upper respiratory tract typically results in secondary lower-respiratory-tract bacterial infection; consequently, control efforts have focused on development of immune responses against primary viral pathogens (2). Although BRD is commonly associated with and studied as a post-weaning disease in beef cattle, it is also an important cause of morbidity among nursing beef calves (5–7).

Bovine coronavirus (BCoV) has been described as an overlooked virus that contributes to the BRD complex, due to contradictory evidence that both implicates and refutes the association between BCoV and BRD (8–11). Some uncertainty regarding contributions of BCoV to BRD may exist because it is commonly recovered from both healthy and sick cattle and is often recovered as a coinfection with other viruses (9). However, at least 2 studies had compelling evidence of reduced BRD treatment risk when calves were seropositive for BCoV (12,13).

Evidence of effectiveness of vaccination against BCoV is relatively scant; however, recent efforts showed the benefits of mucosal vaccine programs through specific and neutralizing antibody production (14) and protection against BRD in the field among commercially raised beef calves post-weaning (12,14,15). However, antibody differences have not yet been identified in calves pre-weaning; it is likely the antibody differences will not be detected, given the effect of maternal antibody presence on antibody production in neonates. Further to this, in a BCoV coinfection challenge study of calves, mucosal priming followed by a systemic booster did not produce signs of severe clinical disease or high rates of virus shedding (14). Importantly, intranasal (IN) BCoV vaccination could also be safely and effectively coadministered with a second IN combination modified live virus (MLV) vaccine with BoHV-1, bovine respiratory syncytial virus (BRSV), and bovine parainfluenza virus type 3 (BPIV3) (16).

Despite some data, apparently no field studies examining effectiveness of BCoV vaccination of neonatal beef calves to control pre-weaning respiratory disease have been published. Our objective was to investigate field effectiveness of IN BCoV prime-boost vaccination on a ranch with a history of BCoV-related BRD, diagnosed by the herd veterinarian through diagnostic testing, including PCR on live and postmortem cases. Specific objectives were to compare BRD treatment pre- and post-booster vaccination in nursing calves, as well as calf mortality, weaning weight, and weaned calf revenue potential between calves that were either vaccinated or not vaccinated with a BCoV vaccine.

MATERIALS AND METHODS

Animal ethics approval was obtained from the University of Saskatchewan’s (Saskatoon, Saskatchewan) University Animal Care Committee’s Animal Research Ethics Board (AUP: 20200029). This research was conducted in accordance with regulations of the University Animal Care Committee and the Canadian Council on Animal Care.

Animals and trial design

Neonatal mixed-breed beef calves born to multiparous cows from February 16 to May 28, 2024, at a commercial ranch in north-central Alberta were enrolled in the study. Cows were vaccinated annually with a combination MLV vaccine that included antigens for bovine herpes virus type 1 (BoHV1), BRSV, BPIV3, and bovine viral diarrhea viruses types 1 and 2 (Bovishield Gold FP5; Zoetis Canada, Kirkland Quebec). The ranch reported previous outbreaks of BRD among neonatal calves aged 10 to 50 d. The ranch’s veterinarian had previously submitted nasal swabs from sick calves to a diagnostic laboratory for multiplex viral PCR; BCoV was associated with 7 of the 12 submitted cases. Otherwise, 1 calf was positive for influenza D virus, 1 was positive for BoHV1, 2 were suspect [near the cycle threshold (Ct) of 37] for BoHV1, and 4 had no viral pathogen identified. However, for the BoHV1-positive or -suspect samples, the Ct values were either near or above the upper cut-point. Within 24 h, the calves had also been vaccinated with a mucosal combination MLV vaccine that included BoHV1 as well as BRSV and BPIV3, and vaccination might have interfered with testing.

Sample size for the study was calculated to achieve an estimated difference in proportions of calves treated for respiratory disease, using a web-based sample-size calculator (https://www.stat.ubc.ca/~rollin/stats/ssize/), with 5 and 10% BRD rates for the 2 study groups. Calves were randomly allocated into either a BCoV vaccine group (VAC) or control group (CON) at birth, using a tool embedded in the commercial herd-management software used by the ranch (TELUS Animal Record Management, Vancouver, British Columbia).

Animal management

The cattle were housed as 1 large group before calving and moved through a calving barn for processing, which included application of unique radio frequency identification tags and dangle identification tags, entry into herd-management software, randomization into study groups, and vaccination. Each dam and calf were then moved from the calving barn into a pen. As pens were of variable size, each was filled to its individual capacity and then subsequent pens were filled until the end of the calving season. The dirt-floor pens ranged in capacity size from 88 to 186 pairs and had 33% porosity wood fencing on 3 sides. The pens shared automatic waterers and were bedded with straw. Cows had ad libitum access to hay. Cattle were held in these pens until the booster vaccination at ~49 d (SD: 7 d), when they were mixed into 1 large group on a 160-acre field where they remained until they were moved to pasture for grazing.

Vaccination

Within 12 to 24 h after birth, each calf in the VAC group was administered a 3.0-milliliter IN dose of MLV vaccine containing BCoV and rotavirus (Calfguard; Zoetis Canada); those in the CON group were not. Intranasal administration of this product was not on the current product label but it had been used successfully in this manner (10,12–14). As per herd management, all calves were administered 2.0 mL of mucosal MLV vaccine containing BoHV1, BRSV, and BPIV3 (Inforce 3; Zoetis Canada) in the contralateral nostril within 12 to 24 h after birth. At ~49 d of age, calves were each administered 2.0 mL of an MLV vaccine (BoHV1, BRSV, BPIV3, bovine viral diarrhea viruses types 1 and 2) that included a bacterin for Mannheimia hemolytica (Pyramid FP5 + Presponse; Boehringer-Ingelheim, Burlington, Ontario) by subcutaneous (SC) injection. Also, at 49 d, a 2.0-milliliter SC dose of an 8-way Clostridium spp. vaccine that contained Histophilus somni antigen (Vision 8 Somnus; Merck Animal Health, Kirkland, Quebec) was administered. At the same time, each surviving calf in the VAC group was administered, by intramuscular injection, 3.0 mL of the same vaccine previously administered IN (Calfguard; Zoetis Canada); those in the CON group were not.

Calves were monitored by trained ranch staff and treated for BRD if observed to have at least 2 of the following clinical signs: lethargy, drooping ears, cough, nasal discharge, respiratory distress, or a rectal temperature > 39.9°C. As per the consulting veterinarian’s standard protocol, calves meeting the case definition were each treated with 40 mg/kg of florfenicol (Florkem; CEVA Animal Health, Guelph, Ontario) by SC injection. Calves were treated in their pens by ranch staff and remained in the pens to convalesce. Treatments were recorded in ranch-management software. Deaths were recorded, but calves were not examined post-mortem due to the distance of the veterinary clinic from the ranch. Monitoring for disease continued after booster vaccination until cow-calf pairs were moved to summer pasture. Calves were weaned at an average age of 258 d (SD: 21 d) and individual body weights at weaning were recorded in ranch-management software.

Nasal swabs

At the time of BRD treatment, deep nasal swabs were collected from 9 calves. For each, the 15-centimeter sterile polyester-tipped swab (Puritan Medical Products Company, Guilford, Maine, USA) was placed into the ventral meatus. The swab was then rotated a minimum of 10× against the mucosa and then placed into nasal swab media (HEPES, FBS, MgS, NaCl, RPMI, fungizone, gentamycin). Swabs were stored at −20°C until they were shipped, on ice, to Prairie Diagnostic Services Inc. (Saskatoon, Saskatchewan) for BCoV PCR analysis using the laboratory’s commercial BCoV PCR (17).

Data analyses

All data were shared by the ranch veterinarian after weaning and then reviewed and analyzed using commercial software (Stata 15; Stata, College Station, Texas, USA). Data collected included calf identification, calf sex, calf allocation (VAC or CON group), date of birth, location (pen) of birth, date of treatment for BRD (if any), date of mortality (if any), and — if the calf was weaned — weaning weight and age. Other data included which 21-day cycle (“cycle of birth”) of the calving season the calf was born into (1, 2, or 3+).

Respiratory disease treatment

Logistic regression adjusted for clustering by pen was used to compare the odds of BRD treatment before booster vaccination and after booster vaccination, as well as total mortality. Treatment of BRD was classified as pre-booster vaccination from birth to 14 d after the booster vaccine was administered. This delay in assigning BRD treatment as post-booster vaccination allowed time for an immune response to the booster vaccine.

More specifically, differences in the odds of treatment for BRD between VAC and CON groups were examined using generalized estimating equations with a logit link function and binomial distribution. Clustering by pen was accounted for with an exchangeable correlation coefficient. Cycle of birth, sex, and an interaction term for study group and cycle of birth were included as fixed effects. If the interaction term was significant, differences between VAC and CON were compared for each cycle of birth. Odds ratios (OR) and 95% confidence intervals (95% CI) were reported.

Potential differences in age of calves when first treated for BRD were compared between VAC and CON groups using Wilcoxon rank sum test. Kaplan-Meier curves for VAC and CON were reported for 2 intervals: birth to booster vaccination and birth to post-booster vaccination. Kaplan-Meier curves for each group were then compared using a log-rank test. For all analyses, values of P < 0.05 represented significant differences.

Weaning weights

Weaning weights were also compared between VAC and CON using linear regression within generalized estimating equations, after assessing normality using a Shapiro-Wilk test accounting for clustering by pen. Non-normally distributed data underwent natural log transformation before analysis and a normal distribution. Other fixed effects in this model included age at weaning and sex. Age at weaning was scaled to 7-day increments. Linearity of the association of age at weaning with weaning weight was examined by adding a squared term for age to the model together with age and testing significance of the polynomial. Results of the model were back-transformed before reporting to reflect geometric mean weaning weights, relative differences in weights among treatment groups, and 95% CI.

Economic analysis/partial budget

Potential economic impact of BCoV neonatal IN prime and systemic boost vaccination was analyzed using a partial budget in Canadian dollars (CAD). Market pricing of vaccines ($5.30/dose) and pharmaceuticals was used to determine costs of vaccination and treatment; in addition, labor costs associated with 2 vaccine administrations [$17/head (hd)] and disease treatment ($10/hd) were included. Each florfenicol treatment was estimated to cost $5.40, based on a 6-milliliter dosage and $0.90/mL product cost. The value of a weaned calf was determined using market data from Alberta (CanFax Canada, Calgary, Alberta) for the 2 wk before and 2 wk after weaning. Market price was averaged by sex and week to determine an approximate value for an average weaned calf, and the derived calf price ($8.66/kg) was applied as an average of heifers and steers to account for potential differences in numbers of heifers and steers in each of the 2 study groups. Differences were calculated for each vaccine, vaccination labor, pharmaceutical, treatment labor, and calf revenue. Total cost difference between groups was subtracted from total revenue difference between study groups to yield the final per-head revenue difference.

RESULTS

In total, 887 calves were enrolled into either the VAC (n = 448) or the CON (n = 439) group within 24 h after birth (Table S1, available online from: Supplementary Materials). Booster vaccination occurred at a mean age of 49 d (SD: 7d); however, because of the ranch’s prolonged calving season, not all calves were boosted by the time of pasture turnout (movement of cow-calf pairs to summer grazing). To address this issue, 1 analysis included all 887 calves enrolled and a 2nd included only the 765 calves that received the booster vaccination (VAC, n = 389; CON, n = 376). Furthermore, effect of immunization on frequency of BRD treatment after booster vaccination was analyzed using only calves that were booster vaccinated and not previously treated for BRD (n = 626: VAC, n = 340; CON, n = 296). Another important factor to control for was effect of pen, especially as some pens housed calves from different cycles of birth (Table S2, available online from: Supplementary Materials). Clustering in pens might have occurred within age groups; however, this was controlled for in all models.

For the 887 calves enrolled in the trial, 16% of VAC and 22% of CON calves were treated for BRD before booster vaccination; therefore, CON calves had 1.5× greater odds of BRD treatment than VAC calves (P = 0.048) (Table 1). Treatment for BRD also differed by cycle of birth, with calves born in Cycle 2 having 2.9× higher odds of BRD treatment than calves born in Cycle 3 (P = 0.01) (Table 1); however, there were no differences between Cycles 1 and 2 or Cycles 3 and 1 (P = 0.25 and P = 0.10, respectively). The effect of vaccination on BRD rate did not vary by cycle of birth (P = 0.53).

TABLE 1.

Treatment for bovine respiratory disease before turnout vaccination for all calves enrolled in the study, comparing bovine coronavirus-vaccinated (VAC) and non-vaccinated (CON) calves (N = 887).

Calves included	Group	n	Number treated	Odds ratio	95% confidence interval		P-value
All calves enrolled
Treatment	VAC	448	72	Reference group
	CON	439	95	1.50	1.03	2.24	0.048
Cycle of birth	1	251	40	1.90	0.86	4.10	0.10
	2	377	95	2.90	1.27	6.64	0.01
	3	259	32	Reference group
Controls and prime-boosted calves
Treatment	VAC	389	59	Reference group
	CON	376	80	1.51	1.27	1.79	< 0.01
Cycle of birth	1	246	38	3.30	1.28	8.52	0.013
	2	368	93	6.06	3.12	11.7	< 0.01
	3	151	8	Reference group

Of the 765 calves that were primed and boosted, 15% of VAC and 21% of CON calves were treated for BRD pre-booster, with CON calves having 1.5× greater odds (P ≤ 0.01) of BRD treatment than VAC calves (Table 1). Both Cycle 2 (OR: 6.2; P ≤ 0.01) and Cycle 1 (OR: 3.5; P = 0.01) calves were more likely to be treated for BRD than Cycle 3 calves (Table 1), whereas Cycles 1 and 2 were not different (P = 0.14). The effect of vaccination did not vary by cycle of birth (P = 0.70).

After booster vaccination and a 14-day hold period had elapsed, 5% of VAC and 7% of CON calves were treated for BRD. The odds of BRD treatment were not different between CON and VAC (P = 0.06) (Table 2). However, Cycle 1 calves were more likely to be treated for BRD (OR: 5.6; P = 0.04) than Cycle 3 calves (Table 2).

TABLE 2.

Treatment for bovine respiratory disease after turnout vaccination, comparing calves that were both primed and boosted against bovine coronavirus (VAC) to non-vaccinated control calves (CON) (n = 626).

Characteristic	Group	n	Number treated	Odds ratio	95% confidence interval		P-value
Treatment	VAC	330	15	Reference group
	CON	296	22	1.72	0.97	3.06	0.063
Cycle of birth	1	208	15	5.62	1.11	28.3	0.037
	2	275	20	5.58	0.89	35.0	0.066
	3	143	2	Reference group

Mean age and median age at treatment for BRD pre-booster and post-booster appeared similar between study groups (Table S3, available online from: Supplementary Materials). However, Kaplan-Meier curves were different between study groups for both birth to booster (P = 0.03; Figure 1) vaccination and birth to post-booster vaccination (P = 0.0008; Figure 2), indicating that the overall rate of BRD treatment was higher for the CON group. The curves appeared similar in shape, agreeing with the interpretation of descriptive data on age at treatment; both suggested a parallel age pattern of disease between study groups.

FIGURE 1.

Comparison of Kaplan Meier pre-booster respiratory disease treatment survival curves between calves vaccinated with modified live intranasal bovine coronavirus at birth (VAC) and non-vaccinates (CON) (P = 0.008; N = 887).

BRD — Bovine respiratory disease.

FIGURE 2.

Comparison of Kaplan Meier respiratory disease treatment survival curves, from birth to pasture turnout, between calves primed at birth with intranasal modified live bovine coronavirus vaccine and boosted subcutaneously (VAC) at ~49 d (SD: 7 d) and non-vaccinates (CON) (P = 0.03; n = 765).

BRD — Bovine respiratory disease.

For the 887 calves enrolled, total pre-booster mortality was 2%. The effect of vaccination on mortality varied by cycle of birth (P < 0.00001). Mortality only differed between study groups for calves born in Cycle 2; in that cycle, the odds of mortality for CON calves were 4.8× higher than for VAC calves (P = 0.001) (Table 3). Two calves from each study group died after booster vaccination and mortality rates were not different (P = 0.30).

TABLE 3.

Mortality from all causes before turnout vaccination, comparing calves vaccinated against bovine coronavirus (VAC) and non-vaccinated controls (CON) (N = 887).

Cycle of birth	Vaccine group	n	Mortality count	Odds ratio	95% confidence interval		P-value
1	VAC	132	3
	CON	119	3	1.05	0.07	16.2	> 0.99
2	VAC	184	1
	CON	193	5	4.77	1.57	14.5	0.001
3	VAC	132	3
	CON	127	1	0.32	0.07	1.49	0.30

Nasal swabs were collected for PCR detection of BCoV among BRD-treated calves; however, it was not possible to determine whether the detected virus was from natural infection or vaccination. Four of the 9 nasal swabs were PCR-positive for BCoV and 3 were negative. Two additional swabs were suspicious, with Ct values above the laboratory’s cut-point of < 37. One swab was positive near the Ct threshold for BoHV1, 3 swabs were positive for influenza D virus, 1 swab was BRSV-positive, and 2 swabs were positive for Mycoplasma bovis. Due to sample-selection error, only 1 vaccinated calf had a swab collected; this calf was the one positive for BoHV1 and was also positive for influenza D virus and Mycoplasma bovis.

Weaning weights differed by group after accounting for age and sex (Table 4); however, the effect of vaccination on weaning weight was consistent across calf age and sex, based on a nonsignificant interaction. The geometric mean weaning weight for VAC calves was 2 kg heavier than for CON calves (P = 0.04) (Table 4). As expected, calves that were older at weaning had a higher weaning weight (P = 0.02), and weaning weight for steers was 17 kg heavier on average than that for heifers (P ≤ 0.01).

TABLE 4.

Comparison of model-predicted geometric mean weaning body weight between calves vaccinated against bovine coronavirus (VAC) and non-vaccinated calves (CON) (n = 741).

Characteristic	Group	Body weight (kg)	95% confidence interval (kg)		Relative difference	95% confidence interval		P-value
Vaccine	VAC	288	279	298
	CON	286	276	296	0.99	0.98	1.00	0.04
Sex	Heifer	278	267	290
	Steer	296	287	305	1.06	1.04	1.08	< 0.01
Age (7-day scaled)		287	277	297	1.01	1.003	1.02	0.02

Overall costs for VAC calves were $26.73/hd (CAD) higher than for CON calves due to the cost of vaccination ($27.60/hd), moderated slightly as the VAC group had a lower average treatment cost per head (Table 5). However, average revenue per calf was greater for the VAC group ($37.23/hd) because VAC calves had higher weaning weights. The net difference in revenue associated with BCoV vaccination was $10.50/hd more than the cost of vaccination, which indicated an economic benefit for vaccination in this scenario.

TABLE 5.

Comparison of costs and revenues between calves vaccinated against bovine coronavirus (VAC) and non-vaccinated controls (CON).

Costs	Description	VAC	CON	Difference/margin
Vaccine	$5.30 × 2 doses	$10.60	$0	$10.60
Labor	$10 for 1st dose, $7 for 2nd dose	$17.00	$0	$17.00
Treatment for respiratory diseasea	Treatment rate (%)	15	21
	Treatment cost per head	$2.31	$3.18	($1.43)
Total costs per head		$29.91	$3.18	$26.73
Revenues	Description	VAC	CON	Difference/margin
	Wean rate (%)	98.5	97.7
	Avg market price ($/kg)b	$8.66	$8.66
	Avg wean weight (kg)	288	286
	Adj calf revenue ($/hd)c	$2457.02	$2419.79	$37.23
Net return		$2427.11	$2416.61	$10.50

^aTreatment cost per calf is 6 mL × $0.90/mL of florfenicol = $5.40/hd + $10/hd labor, for a total of $15.40/hd.

^bAverage market value calculated using average market price of $8.66/kg × wean weight.

^cAdjusted revenue calculation = wean rate × market price ($8.66/kg) × wean weight.

DISCUSSION

Vaccination of neonatal calves against BCoV reduced the odds of BRD morbidity in young suckling beef calves, and increased weaning weight and revenue compared to control calves. At least 2 field studies reported that BCoV vaccination reduced the frequency of BRD treatment compared to non-vaccinated control calves; however, those studies observed post-weaning BRD (12,15). One of the field studies (12) reported that IN priming alone was sufficient to provide protection from respiratory disease. In a comparison of IN prime versus IN prime with an SC boost, antibody responses were best among the prime-boost calves (16). Evidence of effective antibody induction by prime-boost was the motivation for subsequent investigations; prime-boost protected calves from BRD due to natural infection with BCoV (14) and appeared to have variable beneficial effects after BCoV challenge (15,18).

Previous studies (12,15,16,18) used the same commercial vaccine as the current study. Interestingly, 1 field study (15) reported no difference in post-weaning BRD frequency between a group administered the same vaccine used in the current study and a non-vaccinated control group; however, the comparator vaccine group in that study was different from the control group. This might have been due to differences in effectiveness of the 2 vaccines, though there was also no difference between vaccine groups in odds of treatment. Alternatively, the lack of a significant difference between the vaccine used in the present study and the controls reported in the previous study might be explained in part by an overall reduction in virus exposure to control calves, since most calves in that study were vaccinated against BCoV. In a field trial with vaccinated and unvaccinated calves mixed in the same management group, vaccinates might have reduced risk of virus exposure for controls; or conversely, controls might have increased risk of exposure for vaccinates, reducing the ability to detect a difference between groups associated with the vaccine (19). Alternatively, the chance element inherent in a field study could have resulted in lower natural exposure to the virus in 1 vaccinated group versus another. The current study was also subject to similar chance elements since controls and vaccinates were co-housed.

The frequency of BRD treatment in the current study differed before booster vaccination. Therefore, it appeared that a single dose of IN BCoV vaccine in the first 24 h of life was effective in reducing BRD in very young calves. Similarly, in a feedlot study, a single IN dose of BCoV vaccine protected weaned calves in the post-arrival period (12). Protection from BRD could be attributed to an IgA response associated with IN vaccination, as reported for other viruses such as BRSV and BoHV1 (16,20). However, boosting IN-primed calves had a trend in reducing BRD treatment. Whereas trends are not conclusive, the P-value for post-booster difference in BRD treatment odds was 0.06, with an estimated 1.7× greater odds of BRD treatment for the CON group. There were fewer calves treated after the booster and the reduced number of cases likely limited power for this portion of the study.

The current study was conducted on a ranch that experienced outbreaks of BRD in suckling calves before routine systemic vaccination at ~50 d of age, following a protocol described for many other herds in western Canada that did not include BCoV antigen, as it is not considered a core vaccine (21). In the present study, most BRD treatments occurred before booster vaccination (~50 d of age). The lack of a significant difference in frequency of BRD treatment post-booster was likely the result of the timing of BCoV infection and its epidemiology within the herd. The outbreak appeared to have largely subsided before turnout vaccination and subsequently resulted in few post-booster treatments, as suggested by Kaplan-Meier plots flattening for both groups’ curves beyond 50 d.

Previous BCoV vaccination field studies did not detect or did not examine differences in mortality. In the present study, the odds of total mortality were higher among CON calves born in the 2nd cycle. This finding was not unexpected, since the treatment rate for BRD was consistently high in this birth cohort and most deaths occurred in the birth cohort that had the highest treatment rate. The ranch was > 3 h from the veterinary clinic and, as a result, calf postmortem examinations were not feasible. Clearly, the study would have benefited from postmortem examinations of all study calves that died, to determine the cause of death and to detect virus. In the current study, only 1 VAC calf had a nasal swab collected compared to 8 CON calves, and this could have caused selection bias. Interestingly, the VAC calf was not BCoV-positive; thus, in this 1 case, vaccine virus was not detected. However, since CON and VAC calves were co-housed, it could not be determined whether the BCoV CON calves were positive for natural or vaccine virus. For other viruses, vaccine MLV was shed from the upper respiratory tract for a variable number of days post-vaccination (22), meaning that vaccine MLV exposure to CON calves was possible. However, no studies reported that MLV was shed from non-vaccinates exposed to vaccine MLV-shedding calves, and there is no indication in the literature that immune responses occur among control calves exposed to mucosally vaccinated calves.

Previous field studies also did not examine the effect of BCoV vaccination on body weights. Ideally, the current study would have included average daily gain analysis, but the producer did not collect birth weights. However, weaning weights significantly differed between the VAC and CON groups after adjustment for calf age and sex. Higher weaning weight in VAC calves helped to offset costs associated with vaccination.

There was a net economic benefit to vaccination in this herd. When per-head costs of vaccine, treatment, labor, and mortality were subtracted from mean revenue, the net benefit for vaccinated calves was $10.50/hd. In the partial budget analysis, costs of vaccination were offset by the benefits of improved weaning weights and reduced treatment costs and mortality. The analysis used a conservative high value ($17/hd) for labor to administer both vaccines; the labor cost was set to account for the inconvenience of single-dose vials, the only formulation commercially available.

Despite greater odds of morbidity and mortality among non-vaccinates, there was still considerable disease in the VAC group. The ranch treated at least 15% of vaccinated calves in this study and this treatment rate among young suckling beef calves was extreme. In a recently described surveillance network of Canadian beef producers, mean respiratory disease treatment rate among calves from 24 h to 30 d of age was 3.1% (SD: 5.7%). The ranch in the current study would have ranked in the 97th percentile as one of the worst herds for BRD treatments (5).

Viral shedding likely contributed to the high rate of disease among calves. In this study, only 50% of the calves were vaccinated and there was likely exposure to disease pressure from virus shed by case animals. As the CON group had more cases, it is likely that their mixture with the VAC calves contributed to the risk of disease for VAC calves, despite their vaccine status. The level of vaccination, 50%, would not be expected to induce herd immunity, as BCoV is shed in high amounts among infected cattle (5,11,12). The intensity of management likely contributed to virus exposure. Calves and their dams likely had close contact, which would enhance viral spread. Given the high incidence of BRD in this herd, immunity derived from vaccination might have been overwhelmed and contributed to disease among vaccinated calves. Regardless, differences identified within this study supported previous field and experimental study findings that BCoV-vaccinated calves were protected from natural challenge (14) and BCoV vaccination likely resulted in immune induction (16). Therefore, BCoV vaccination should be considered in herds that have diagnosed BCoV BRD outbreaks among suckling calves.

Altogether, data generated in this field study indicated that IN administration of BCoV vaccine to neonatal calves reduced odds of BRD treatment and mortality in young suckling beef calves. The economic benefit of BCoV vaccination was attributed to improved weaning weights and reduced treatment costs.