New Vaccine for Cattle Protects Against Fetal Calf Loss From EBA – Anatomy of a Vaccine Development

 

A new vaccine just approved by the USDA in September promises to turn the tide against Epizootic Bovine Abortion, also known as the foothill abortion disease, that has caused devastating losses in range cattle exceeding $10 million annually in California, Oregon and Nevada.

 

The vaccine, developed through extensive research at the University of Nevada, Reno and the University of California, Davis, was commercialized by Hygieia Biological Laboratories of Woodland, California, and is now available to the cattle industry. This license marks a pivotal advancement in decreasing those substantial calf losses and comes as the result of decades of work by generations of scientists and cattle producers.

 

“It was really neat to see the pieces come together over the years as a result of all the effort that was put into this project,” Mike Teglas, a partner in the project and a professor and veterinarian in the University of Nevada, Reno’s College of Agriculture, Biotechnology & Natural Resources, said. “I have a definite sense of satisfaction that I was able to play a role in the development of this vaccine.”

 

First described by U.C. Davis scientists in the 1950s in the western foothills of the Sierra Nevada mountains of California, the disease, EBA, only affects pregnant cattle and can be responsible for losses of up to 100% of the year’s calf crop in susceptible herds.

 

In 1985, U.C. Davis Professor Jeffrey Stott joined the faculty at the Veterinary School and began working on the disease with current collaborator Myra Blanchard, also of U.C. Davis Veterinary School.

 

“As a member of our research team and a faculty member in an instruction and research university, there could be no greater feeling – maybe a Nobel Prize would sit higher on the shelf – than seeing the results of our efforts,” Stott said. “We are all expected to conduct both instruction and research, but to create something that will have, and is already having, a major positive impact on the cow/calf industry is what makes this accomplishment so much more meaningful and rewarding.”

 

 

A decade of vaccine trials were conducted to establish the safety and efficacy of the product, which is now available commercially to the cattle industry through livestock veterinarians. The USDA Center for Veterinary Biologics issued the conditional license for the vaccine after two years of trials of the Hygieia product.

 

"The vaccine has proven safe and phenomenally effective; the fervor for its widespread availability is palpable among cattle producers,” Stott said.

 

The decades of perseverance of the researchers on this project shows the value of land-grant universities to the communities they serve.

 

“It’s translational research such as this that we all strive to achieve, completing our land-grant loop of research, education and outreach with a solid solution to a real-world problem,” Bill Payne, dean of the University of Nevada, Reno’s College of Agriculture, Biotechnology & Natural Resources, said. “It’s not just research for research’s sake. Mike’s untiring work over the long-haul, and the work of his predecessors, on identifying the disease and building a vaccine is impressive work that makes us all proud. Especially impressive is the team’s work with the relatively small pharmaceutical company to commercially produce this after the big companies shunned it for years because of (in their view) a relatively small, niche market for this particular disease.”

 

Industry representatives are also excited about the new vaccine.

 

“The licensing and availability of this vaccine is monumental for the beef cattle industry,” Mark Lacey, president of the California Cattlemen’s Association, said. “For generations producers have had to manage incredible losses from foothill abortion.

 

“From the University’s research, to the generous donations of cattlemen and the Livestock Memorial Research Fund, to the production and commercialization of the vaccine, it has been a long haul. I couldn’t be happier to say that we are finally here.”

 

 

Teglas has been leading the EBA research at the University of Nevada, Reno, since 2006, after leaving U.C. Davis where he had been studying the origins and causes of the disease as a graduate student. He continued the University’s long-time collaboration with lead researcher Jeffrey Stott and Myra Blanchard from the School of Veterinary Medicine at U.C. Davis. At that point Stott’s lab had utilized a molecular genetic technique to finally identify the pathogen that caused foothill abortion disease.

 

But earlier research on the cause of EBA had gone on for decades without success. Scientists were unable to identify a pathogen as the source of the disease and were unsure about how it was transmitted. In one old study, U.C. Davis researchers even housed pregnant cattle in pens hung 8 feet off of the ground in order to determine if flying insects versus those confined to the ground served as vectors for the disease.

 

“Eventually, researchers were able to pin transmission on the pajaroello tick, Ornithodoros coriaceus, a species of soft tick that is commonly found in the Sierra Nevada and coastal ranges of California,” Teglas, also an expert on tick-borne diseases, said. “The distribution of the disease mirrors the distribution of its tick vector and has now been identified in the mountainous regions of California, northern Nevada, southern Oregon and southern Idaho.”

 

In 1992, Stott and Blanchard had teamed up with University of Nevada, Reno Professors Mark Hall in the Center for Molecular Medicine and Don Hanks in the School of Veterinary Medicine to try to identify the agent causing the disease in an effort to develop a method to grow the pathogen in the lab.

 

In one experiment, using cattle at the University of Nevada, Reno’s 900-acre Main Station Field Laboratory at the east end of Reno, the team glued cloth hats – with a zipper sewn into the hats – onto the cattle; the zipper would be opened in order to pour 100 hungry pajaroello ticks into the hats to infect the cattle. But the researchers ability to recreate the disease in a consistent manner was still hindered by the lack of an identifiable pathogen in those fetuses lost to the disease.

 

 

A breakthrough came along when Stott’s lab used the molecular genetic technique to finally identify the EBA pathogen, a bacteria that was more closely related to slime molds than it was to other bacterial pathogens of animals.

 

“With this knowledge in hand, I was able to test ticks across their range, determine their infection status and assess whether the tick vectors were being moved around the West by human activities such as the shipping of cattle,” Teglas said.

 

Another important discovery was made in those first few years of his new career at the University of Nevada, Reno, one that created the foundation for the eventual development of a vaccine.

 

Stott and Blanchard found that they could infect mice that lacked a competent immune system with the bacteria and that tissues from these animals contained considerable amounts of viable pathogenic bacteria. 

 

“This led to our ability to reliably infect large numbers of susceptible cattle for research purposes,” Teglas said. “We quickly discovered that cattle exposed to the bacteria in their first year would develop immunity to subsequent infections for another two years without additional exposure to the pathogen.”

 

The research team, once again using the cattle at the University’s Main Station Field Lab inReno, used the new bacterial inoculum to sensitize cattle to the bacteria when they were not pregnant to see if that could serve as a potential source of immunization against the disease.

 

“For the EBA vaccine studies we used the heifers, young females, that were born the previous year and were going to be pregnant for the first time – about 50 to 70 animals a year,” Teglas said. “The benefit of doing research at the Main Station was that we could keep animals for two or three years in a row and follow up on them over time.”

 

There are about 520 head of cattle (males and females) at the Main Station Field Lab in a given year that are available for use in research by faculty on campus.

 

 

“The Main Station was vital to our research efforts since we had access to a large group of susceptible cattle that could be manipulated and monitored much more closely than in a private cattle herd,” Teglas said. “We used the bacterial inoculum to create an attenuated vaccine product and began to test its ability to protect pregnant cows against developing EBA. The results were immediately impressive, with 100% of the vaccinated pregnant cattle producing live calves after being experimentally infected.”

 

The team began studies to test the efficacy and safety of the product following USDA guidelines. Stott met with representatives from some of the largest drug manufacturers to see if there was interest in commercialization of a vaccine, but the big companies considered it a regional disease and not widespread enough to make an investment.

 

The final steps necessary to fully approve the vaccine by the USDA were completed this summer, and now beef cattle producers across the country can order the product directly from the Hygieia, which made the vaccine a reality.

 

“Jeff and Myra need to get the credit for spearheading this research and keeping the faith even when we had to start all over again,” Teglas said. “It’s a fascinating disease and there are still lots of questions waiting to be answered. I look forward to continuing working with them on EBA into the future.

 

“In fact, we are working on a project now investigating the potential of in-utero vaccination/protection of the fetus with the EBA vaccine. If successful the work could have lots of implications for development of future vaccines aimed at producing a calf that is already born with protection against cattle pathogens, something that is unavailable to producers today.”

 

The team has ongoing foothill abortion research projects and are developing new ones.

 

“Research is what we love and what we do,” Stott said. “Our ongoing foothill abortion research projects, are directed at furthering our understanding of the disease, its geographic distribution and new disease management strategies that will incorporate the vaccine as an important component in our translational research, of making research useful for our constituents – the cattle industry.” 

 

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