Vaccination Programs to Improve Calf Health

Background 

Developing new vaccines is very costly, but we can potentially make the vaccines we already have work better. There is some evidence that “heterologous” vaccine protocols (e.g., giving an intranasal modified-live vaccine (MLV) for the initial vaccination and boosting with an injectable killed vaccine) or using different vaccine routes (e.g., initial vaccination with an intranasal and boosting with an injectable) may provide better immune protection than a “homologous” vaccine protocol, where the same vaccine type and route are used for both the initial vaccination and the booster.

The main idea, regardless of the heterologous vaccination method used, is that priming and boosting neonatal calves are likely important for the development of effective immunity in young calves. Prime-boost methods such as these might aid in the development of immune memory that persists in the pre- and post-weaning periods.

The immediate challenge, and the reason alternative methods of immune development are being sought, is that young calves have high concentrations of maternal antibody in their blood from colostrum. While these maternal antibodies are desirable and provide protection to the young calf, they also interfere with the response to vaccines. Therefore, it has been proposed that priming young calves with an intranasal vaccine, which bypasses interference from maternal antibodies, and later boosting with an injectable vaccine will elicit a more robust immune response, with memory persisting through periods of high-disease risk, such as weaning.

Objectives

Provide tools that will decrease the risk of pneumonia or bovine respiratory disease (BRD) in calves and reduce the use of antimicrobials for prevention and treatment of BRD through:

• Using a multiple viral challenge model to compare the disease sparing effect of heterologous and homologous vaccine protocols in a controlled study.
• A large-scale field study to compare the effectiveness of the bovine coronavirus (BCoV) prime-boost protocols in reducing BRD morbidity and mortality at weaning in a herd with previously diagnosed BCoV pneumonia among its calves in the pre- and post-weaning periods.
• Using a multiple viral challenge model to compare the disease sparing effect of intranasal prime – systemic boost vaccination to the current industry standard of systemic prime with no booster in a controlled study.

What they Did 

Study 1: This team used different vaccines that both protect against infectious bovine rhinotracheitis (IBR), bovine respiratory syncytial virus (BRSV), parainfluenza virus (PI3) and bovine coronavirus (BCoV). In the first study, calves were vaccinated at birth with an intranasal modified-live vaccine against BRSV, IBR, PI3 and BCoV. At spring turnout, half were boosted with an injectable modified-live vaccine and half with an injectable killed vaccine. At weaning, they were challenged with BRSV, PI3 and BCoV. Animal health and immune response measures, including effects on lungs, were recorded.

Study 2: Using some of the findings from the initial trial, a field study compared the effectiveness of two BCoV vaccination protocols to a non-BCoV vaccinated group to evaluate pneumonia outcomes. A total of 471 commercial calves were enrolled into the study; vaccine group 1 (n = 160), vaccine group 2 (n = 160) and control group (n = 151).

Vaccine group 1 (Bovilis Coronavirus) and vaccine group 2 (Calfguard) were vaccinated intranasally with a MLV at spring turnout and boosted by injection at two weeks before weaning with the same commercial product. All calves including controls were also administered a three-way intranasal and injectable BVDV vaccine at turnout and the same five-way viral injectable vaccine at pre-weaning vaccination. The calves were then abruptly weaned and transported to a paddock at the home ranch. The calves were followed for 45 days post-weaning; respiratory treatments, total treatment and mortality rates were recorded.

Study 3: Similar to the first study, this study compared vaccine protocols, followed by a challenge with multiple viruses (i.e., BRSV, PI3) at weaning. The calves were enrolled into either a prime-boost group or an injectable-only group. The prime-boost group was vaccinated at birth with the same intranasal vaccine as in the first study and boosted with the same injectable modified-live vaccine at spring turnout. The injectable group received no vaccine at birth but was vaccinated at turnout with the same injectable modified-live vaccine. The calves were then pastured for the summer and abruptly weaned in the fall. On the day after weaning, the calves were challenged with BRSV and PI3. Similar health and immune response measures were recorded in the post-challenge period.

Study 4: This field study was conducted on a commercial ranch with a relatively long calving season (mid-February through May) and a history of BCoV outbreaks. Shortly after birth, 900 calves were given intranasal Inforce 3 (against BHV1, BRSV and PI3). At the same time, half of the calves received Calfguard intranasally. This vaccine is an oral scour vaccine that targets coronavirus and rotavirus and is labelled for oral use. Cow-calf pairs with similar calving dates were penned together until booster vaccinations were given at roughly 49 days of age. All calves were boostered with Pyramid FP5 + Presponse (BHV1, BRSV, PI3, BVD types 1 & 2 and Mannheimia) and given Vision 8 somnus (eight-way clostridial vaccine with Histophilus).

Calves that had been given Calfguard at birth were boostered with Calfguard by injection, but the other half of the calves weren’t. All pairs were turned into a larger quarter-section field where calf health was monitored until they were moved to summer pasture. Health was monitored and economic analyses were conducted.

What they learned

Study 1: Although mild disease was observed in both groups, it appeared that they were both equally protected from clinical disease. Both groups also appeared to have similar severity of lung lesions and were spared from severe lung lesions. Overall, the indicators of lung lesions showed that the lungs were well protected from severe disease. With regards to immune response to challenge (i.e., how well immunity was built by each of the vaccination protocols), both groups appeared to have developed immunity that was long-lasting and resulted in good subsequent immune responses to all three viruses at challenge. Overall, the immunity results indicated both prime-boost protocols induced immune “memory” out to weaning.

Differences between the two groups were seen when looking at virus shedding. Virus shedding occurs when calves are infected with the virus, and the virus has the opportunity to replicate (reproduce). Viral replication is important to consider because it is the source of disease spread within a given pen/group of calves. If severe enough, it can lead to an outbreak with a large number of cases. The group that was boosted with a killed vaccine had less shedding of BRSV and PI3 than the group boosted with a MLV. For BCoV, the opposite was true: the MLV-boosted group shed less than the killed vaccine boosted group.

Study 2: Group 1 (Bovilis Coronavirus) had fewer total treatments (calves treated for any reason) and fewer cases of pneumonia than the control group that was not vaccinated against BCoV. No differences were found when comparing Group 2 (Calfguard) with Group 1 (Bovilis Coronavirus) or Group 2 (Calfguard) with the control group (not vaccinated against BCoV). The findings of Group 2 (Calfguard) are a bit more difficult to interpret, but since protection was observed when this vaccine was used in Study 1, it is likely that it is effective. Both vaccine groups and the control group were all managed together; there was likely an overall healthy pen effect. A healthy pen effect means that the non-vaccinated calves were protected from disease because they were housed with a large number of immunized animals. The health/immune improvements in the vaccinated calves resulted in spillover protection for the control/unvaccinated calves. This is a good example of herd immunity in practice. Study 1 gives us an example of how this spillover protection might have occurred. In Study 1, there was less BCoV shedding among the modified-live boosted calves. In this field study, only MLV was used, and there might have been reduced viral shedding, which in turn led to reduced exposure to BCoV and, therefore, lower pneumonia risk across all study groups.

Study 3: Similar to Study 1, both groups appeared to be spared from severe clinical disease. However, the prime-boost group had significantly fewer lung lesions/pathology than the injectable group. The prime-boost group overall had very mild indications of lung pathology, similar to both groups in Study 1. By comparison, the injectable group was quite severe. The prime-boost group also had much less viral shedding post-challenge (for both BRSV and PI3) than the injectable group.

Study 4:

Effect of calving period: Over a quarter of the calves were born in the first three weeks of the calving period, 42% during the second three weeks, and 29% were born later. Before the calves went to pasture, pneumonia treatment rates were higher among calves born during the second three weeks than for calves born in the first three weeks or calves born at the end.

Pneumonia before turnout (in group pens): Pneumonia treatment rates were significantly lower for calves that had been vaccinated against coronavirus (16%) than for calves that hadn’t (21%). Mortality rates were also lower for calves that had been vaccinated against coronavirus, especially among the calves born during the second three weeks of the calving season that experienced the most pneumonia. In that second cycle, 0.5% of the calves that had been vaccinated against coronavirus died, compared to 2.6% of calves that weren’t.

Pneumonia after turnout: To make sure pneumonia relapses didn’t muddy these results, the comparison of differences in post-turnout pneumonia only included calves that had not been treated for pneumonia in the group pens. After calves were turned into the larger field, 4.5% of the calves that were vaccinated against coronavirus were treated for pneumonia compared to 7.2% of the calves that weren’t. This difference was nearly statistically significant.

Economics: Calves that had been vaccinated against coronavirus weighed 4.5 lbs more than those that weren’t. Per-head vaccination costs were $27.60 higher for calves that had been vaccinated against coronavirus because of the added vaccine costs ($10.60) and labour ($17) associated with the two doses of the Calfguard vaccine. On the other hand, calves that had been vaccinated against coronavirus had lower treatment costs ($2.31 vs. $3.18) and a higher weaning rate (98.5% vs. 97.7%) than those that hadn’t been. Putting all this together with their heavier weaning weights, calves vaccinated against coronavirus netted $10.50 per head more than the calves that hadn’t been vaccinated.

what it means

Altogether, these studies indicate that vaccinating (priming) young calves with an intranasal vaccine and boosting them with an injectable vaccine resulted in good protection and development of a robust immune response that likely developed immune memory persisting to the high-risk weaning period. It appears that both killed-vaccine and modified-live-vaccine boosting provide similar protection, with some important nuances, such as viral shedding potential.

Overall, it appears that prime-boost provides superior lung protection and a lower potential for virus shedding than a protocol that uses only a single injection of a modified-live vaccine at a young age. Also, these findings also suggest that a BCoV prime-boost approach may be particularly useful if the herd has experienced previously diagnosed BCoV pneumonia outbreaks.