New vaccine for cattle protects against fetal calf loss due to 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 foothills abortion disease, which has caused devastating losses in cattle over $10 million per year 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 for the beef industry. This license marks a breakthrough in reducing these substantial calf losses and is the result of decades of work by generations of scientists and cattlemen.

“It was really cool to see the pieces come together over the years through all the effort that went into this project,” said Mike Teglas, project partner and professor and veterinarian at the University of Nevada, Reno’s College. of agriculture, biotechnology and natural resources, said. “I have a certain feeling of satisfaction to have been able to play a part in the development of this vaccine.”

First described by scientists at UC Davis in the 1950s in the western foothills of California’s Sierra Nevada Mountains, the disease, EBA, only affects pregnant cows and can be responsible for losses of up to ‘to 100% of the year’s calf harvest in sensitive herds.

In 1985, Professor Jeffrey Stott of UC Davis joined the veterinary school faculty and began working on the disease with current collaborator Myra Blanchard, also of the UC Davis veterinary school.

“As a member of our research team and a faculty member of a teaching and research university, there could be no greater feeling – perhaps a Nobel Prize would be higher on the list. shelf – than to see the results of our efforts,” Stott said. “We are all expected to conduct both education and research, but creating something that will, and is already having, a major positive impact on the cow/calf industry is what makes this achievement so much more meaningful and rewarding.”

Decade of vaccine trials

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

“The vaccine has proven to be safe and phenomenally effective; the fervor for its wide availability is palpable among cattle farmers,” Stott said.

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

“It’s translational research like this that we all strive to achieve, completing our loop of research, education and outreach with a solid solution to a real-world problem,” said Bill Payne, Dean from the University of Nevada, Reno’s College. of agriculture, biotechnology and natural resources, said. “It’s not just research for research’s sake. Mike’s tireless work over the long term and the work of his predecessors to identify the disease and develop a vaccine is impressive work that we are all proud of. The team’s work with the relatively small pharmaceutical company to produce it commercially after the big corporations shunned it for years due to (in their view) a relatively small niche market for this particular disease is particularly impressive. .

Industry representatives are also enthusiastic about the new vaccine.

“The approval and availability of this vaccine is monumental for the beef cattle industry,” said Mark Lacey, president of the California Cattlemen’s Association. “For generations, producers have had to deal with incredible abortion losses in the foothills.

“From University research, to generous donations from breeders and the Livestock Memorial Research Fund, to vaccine production and commercialization, it has been a long road. I couldn’t be happier to say we’re finally here.

The long-standing collaboration continues

Teglas has led EBA research at the University of Nevada, Reno since 2006, after leaving UC Davis where he studied the origins and causes of the disease as a graduate student. He continued the University’s longstanding collaboration with principal investigator Jeffrey Stott and Myra Blanchard of the UC Davis School of Veterinary Medicine. By then, Stott’s lab had used a molecular genetics technique to finally identify the pathogen responsible for Foothills Abortion Disease.

But previous research into 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 how it was transmitted. In an old study, researchers at UC Davis even housed pregnant cows in pens suspended 8 feet off the ground to determine if flying insects versus those confined to the ground served as disease vectors.

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

In 1992, Stott and Blanchard teamed up with the University of Nevada, Professors Mark Hall of Reno at the Center for Molecular Medicine, and Don Hanks at the School of Veterinary Medicine to try to identify the causative agent of the disease with the aim of developing a method to grow the pathogen in the laboratory.

In one experiment, using cattle at the University of Nevada, Reno’s 900-acre main station field laboratory on the east end of Reno, the team glued cloth hats – with a sewn zipper in hats – on 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 consistently recreate the disease was still hampered by the lack of an identifiable pathogen in fetuses lost to the disease.

Breakthrough

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

“Using this knowledge, I was able to test for ticks throughout their range, determine their infectious status, and assess whether tick vectors were being moved west by human activities such as shipping livestock,” Teglas said.

Another important discovery was made during the early years of his new career at the University of Nevada, Reno, which laid the groundwork for the eventual development of a vaccine.

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

“This allowed us 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 further exposure to the pathogen.”

The research team, again using cattle from the university’s main station field laboratory in Reno, used the new bacterial inoculum to sensitize cattle to the bacteria when not pregnant to see if this could serve as a potential source of immunization against the disease.

“For the EBA vaccine studies, we used the heifers, the young females, that were born the year before and were going to be pregnant for the first time – about 50 to 70 animals a year,” Teglas said. “The advantage of doing research at the main station was that we could keep animals for two or three consecutive years and track them over time.”

There are approximately 520 head of cattle (male and female) at the Main Station Field Laboratory in any given year that are available for use in research by faculty on campus.

Main Station Field Laboratory Supports EBA Research

“The main station was vital to our research efforts since we had access to a large group of susceptible cattle that could be handled 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 testing its ability to protect pregnant cows against the development of EBA. The results were immediately impressive, with 100% of vaccinated pregnant cattle producing live calves after being experimentally infected. »

The team began studies to test the efficacy and safety of the product according to USDA guidelines. Stott met with representatives from some of the biggest drugmakers to see if there was interest in bringing a vaccine to market, but the big companies saw it as a regional disease and not widespread enough to make an investment.

The final steps necessary for full USDA approval of the vaccine were completed this summer, and beef cattle producers nationwide can now order the product directly from Hygieia, making the vaccine a reality.

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

“In fact, we are working on a project that is currently investigating the potential for in utero vaccination/protection of the fetus with the EBA vaccine. If successful, the work could have many implications for the development of future vaccines aimed at producing an already born calf with protection against livestock pathogens that is not available to producers today.

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

“Research is what we love and what we do,” Stott said. “Our ongoing abortion research projects in the foothills aim to deepen our understanding of the disease, its geographic distribution, and new disease management strategies that will incorporate vaccine as an important part of our translational research. , to make research useful to our constituents – the livestock industry.”

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