We often hear that cattle respond best to vaccinations when they are healthy, well-nourished and relatively free of physical and psychological stress. In fact, vaccine labels typically specify the product should be administered to healthy cattle, prior to exposure to disease.
And yet, based on convenience, tradition and a perception of urgency, feedyards often vaccinate calves with modified live virus (MLV) vaccines upon arrival, after they've been weaned, comingled, loaded, shipped, shrunk and stressed. Many feedyards give high-risk arrivals a day or two of rest and acclimation prior to initial processing, but for optimum vaccine results, that might not be enough. Results of new research indicate a longer delay could boost MLV vaccine efficiency, especially when combined with the use of an immunostimulant to reduce the impact of respiratory disease.
The research project, recently reported in the peer-reviewed journal Bovine Practitioner, was an unusual collaboration between two competing animal-health companies, Boehringer Ingelheim Vetmedica, Inc., and Bayer Animal Health. It explored the effects of delayed respiratory MLV viral vaccine (Pyramid 5) with or without the inclusion of an immunostumulant (Zelnate) on feedlot health, performance and carcass merits of auction-market-derived feeder heifers.
Veterinary Research and Consulting Services in Greeley, Colo., led by Del Miles, DVM, MS, helped manage the trial.
The researchers note that BRD remains the most economically damaging disease syndrome in beef production, with direct costs associated with death loss compounded by indirect costs for treatment, lost performance and reduced carcass values. They also note the multi-factorial nature of the disease syndrome, which involves numerous pathogens and interactions between host susceptibility, pathogens, and the environment.
They point out that Mannheimia haemolytica serotype A1 has been identified as the most common bacterial pathogen in BRD during the receiving period, with prevalence ranging from 65 to 75%. Fibrinous pneumonia ascribed to M. haemolytica, is the most important cause of BRD mortality.
M. haemolytica routinely colonizes the nasopharynx and tonsillar crypts in cattle. The opportunistic pathogen gains access to the lungs when host defenses are compromised by stress and/or viral-induced immune dysfunction, the researchers note. This process makes bovine respiratory disease one of the best-known examples of stress-associated infectious disease.
We also know that stresses associated with weaning, transport, comingling, castration, dehorning and feedlot processing increase plasma cortisol concentrations and challenge the immune system.
Texas A&M animal scientist John Richeson has conducted research on stress-induced immunosuppression in cattle, and particularly on vaccine responses. In illustrating the stress and disease exposure feeder calves often experience, he describes a typical scenario.
¬∑Tuesday: Calves are separated from their dams and transported to a market.
¬∑Wednesday: Calves are handled and sold through the market, and likely exposed to BRD viruses.
¬∑Thursday: Calves are comingled on a truck, transported to an order-buyer facility and comingled again.
¬∑Thursday overnight: Calves are transported to a feedyard, disrupting their circadian rhythms.
¬∑Friday: Calves are unloaded at the feedyard.
¬∑Saturday: Calves are processed at the feedyard, including administration of a MLV vaccine.
Given those experiences, he says, it should come as no surprise when those calves suffer a BRD outbreak about 14 days after arrival.
Richeson says research has shown acute stress can actually help boost the immune response, but chronic stress suppresses immunity. Also, while a MLV vaccine administered to stressed calves can provide an enhanced antibody response, it also can contribute to chronic stress. Several studies comparing MLV vaccination upon arrival versus delayed for 14 days have shown reduced BRD cases in the delayed-vaccination calves, while some similar studies have found no difference.
Richeson stresses the difference between vaccine efficacy and vaccine efficiency. A strong response in terms of antibody titers suggests vaccine efficacy. Vaccine efficiency refers to the actual results in terms of reduced morbidity and mortality and improved performance. So, a vaccine could be efficacious, providing a good antibody response, but not be efficient due to external factors such as chronic stress. MLV vaccine antigens, although attenuated, could contribute to that chronic stress in new arrivals.
Delaying administration of the MLV vaccine has nothing to do with the vaccine response, Richeson says. It relates instead to removing an additional challenge during a period of stress-induced immunosuppression, while providing later protection against BRD viruses.
Testing the theory
This leads to the recent trial exploring a 30-day delay in MLV vaccine, along with using an immunostimulant in high-risk calves.
Previous research has shown that stress from the marketing and transport process can last as long as 15 days after calves arrive at the feedlot, based on serum hemolytic complement concentration. Several prior research studies have explored the possible benefits of delaying vaccination in feedyard cattle, allowing arrivals to recover from those stressors before calling on their immune systems to respond favorably to the vaccine.
In this trial, researchers delayed administration of the modified-live respiratory viral vaccine for 30 days in test groups. Within the same trial, they also evaluated the use of the immunostimulant. The objectives of the study were to evaluate the potential benefits of delaying the MLV vaccine until stress and M. haemolytica challenges had declined, and also examine if the addition of a DNA immunostimulant would improve health and performance outcomes in a large commercial feedlot setting.
The trial, involving 5,179 high-risk heifer calves in 60 pens, included four treatment groups of 15 pens:
¬∑Delayed vaccine at 30 days.
¬∑Vaccine on arrival and at 30 days.
¬∑Immunostimulant on arrival and delayed vaccine at 30 days.
¬∑Immunostimulant and vaccine on arrival and revaccination at 30 days.
The arrival protocol for all the animals included Mannheimia haemolytica toxoid, tilmicosin, moxidectin, oxfendazole and determination of pregnancy status
The modified-live vaccine used in this trial (Pyramid 5) contains antigens against infectious bovine rhinotracheitis virus (IBRV), parainfluenza-3 virus (PI3V), bovine viral diarrhea virus types 1 and 2 (BVDV), and bovine respiratory syncytial virus (BRSV). The researchers administered 2mL of the vaccine subcutaneously in the right neck. As per label instructions, the researchers administered the 2mL of the DNA immunostimulant intramuscularly in the left neck.
At 60 days on feed, covering a period that typically brings the highest incidence of respiratory disease, the researchers found no significant differences between the treatment groups in the incidence of cattle treated once for respiratory disease. However, the delayed vaccination groups, with or without the immuneostimulant, had a significantly lower percentage of calves treated twice.
As for the immunostimulant treatment, the researchers observed no significant difference in the percentage of calves treated once or twice for BRD during the first 60 days on feed, but they did see a reduction in third treatments. Notably, they did see a significant reduction in the percentage of BRD mortality and overall mortality in the immunostimulant groups, suggesting the product positively influenced the survivability of those calves that were treated for respiratory disease.
The researchers also evaluated health outcomes at 116 days on feed, which corresponds with the average time of re-implanting. They found that the delayed-vaccination group had a reduced incidence of retreatment for BRD and a lower overall retreatment risk. Inclusion of the immunostimulant was associated with a decrease in BRD and overall mortality and tended to decrease case fatality risk
At closeout, the data show 25.8% of the heifers were treated for BRD and 10.6% were treated more than once. Also, 270 or 5.2% of the heifers died prior to study completion with 190, or 3.7% attributed to respiratory disease.
Across all pens, mean retreatment risk for the delayed-vaccination groups was 37.05%, compared with 43.97% for the heifers vaccinated upon arrival. The data also show a reduction in BRD mortalities in the delayed vaccine groups compared with those vaccinated on arrival, but the difference was not statistically significant.
In closeout data from this study, cattle receiving the immunostimulant had lower overall mortality and trended toward lower BRD mortality and case fatality risks. Across all pens, the average overall mortality was 4.36% in groups that received the immunostimulant versus 5.61% for those that did not. BRD mortality followed a similar trend, averaging 2.99% in treated groups versus 3.96% in groups that did not receive the immunostimulant.
In this study, the researchers concluded that delaying of the MLV vaccine for 30 days resulted in a significant decrease in the number of calves requiring additional treatment for BRD. They suggest this delay "may have provided the opportunity for treated cattle to respond more favorably because the interaction between stress and MLV antigens was not a factor in convalescence or clinical display for the delayed vaccinate cattle."Also, the inclusion of a DNA immunostimulant "consistently improved survivability as evidenced by a significant reduction in total mortality at 60 days, 116 days and close out, resulting in a 22% reduction in overall death loss."
A new paradigm
BIVI technical services veterinarian Jerry Woodruff, DVM, one of the authors of the research report, says one underlying factor in this work is that animal-health outcomes have not improved in recent years, in spite of advancements in technology and cattle management. Transition to the feedyard "is a whole new world for calves," Woodruff says, noting that stress likely impacts the immune status of medium-risk cattle as well as high-risk.
Delayed vaccination represents a paradigm shift for cattle feeders and feedyard veterinarians who for years have vaccinated new arrivals as soon as possible, Woodruff adds. He expects it will take time for more operations to evaluate and adopt delayed vaccinations for high-risk calves.
It is important to note that the researchers in this trial did not eliminate all preventative measures at arrival, Woodruff adds. The cattle received the bacterin against bacterial pneumonia and mass medication for BRD prevention.
As often happens, Woodruff says the trial created as many questions as answers, such as whether delaying MLV vaccination could benefit lower-risk cattle, and whether delaying some other processing steps could reduce stress and improve animal health.
Practice mirrors research results
Feedyard consultant Del Miles, DVM, MS, who operates Veterinary Research and Consulting Services in Greeley, Colo., helped execute the study. Even before the study was completed, early results convinced him to begin applying the concept in his clients' feedyards. Where clients agreed, he has begun delaying use of the MLV respiratory vaccination in high-risk cattle for 30 days after arrival, and he says clinical experience has matched the results of the study. He also uses the immunostimulant in high-risk calves in client yards and again has seen results similar to those from the study. He notes one feedyard in particular, where results with lightweight Holstein steers have exceeded those in the study.
In low-risk yearlings, he continues to vaccinate upon arrival to avoid an additional trip through the processing area. Also, when low-risk ranch calves arrive with documentation they received a 5-way MLV viral vaccine within the last six months, he doesn't repeat the vaccination on arrival.
In most cases, his feedyard clients who delay vaccinations in high-risk calves use processing protocols similar to that in the study, including a Mannheimia haemolytica toxoid, deworming and external parasite control as needed.
Several of these feedyards delay implants for 30 days as well as the MLV vaccine. Richeson suggests there also could be a benefit to delaying use of a dewormer for high-risk feeder cattle. Deworming on arrival, when parasite loads are high, could result in inflammatory response and additional stress, he says. Allowing calves to shed most of the parasites and acclimate to the feedyard, and deworming at 21 to 30 days could help prevent early setbacks in performance.
On a related topic, Miles notes that feedyards regularly see spikes in morbidity during the early period which they attribute to respiratory viruses and possibly to lack of efficacy in their vaccines. But in many cases, he says, blood and serum samples do not show an increase in viral antibody titers, suggesting other causes such as stress-related bacterial infections. More research, such as paired serum studies, will be needed to determine whether these cases are viral in nature and whether they have relevant meaning with regard to vaccine efficacy.