In recent years, mRNA vaccine technology and all its promises have drifted into public discourse. This year, the possibility of an mRNA vaccine made its way into the beef world, sparking debates, rumors and uncertainty, prompting public statements from major industry leaders.
The reality is that this technology is not yet approved for use in cattle. Rather, this new generation of vaccines is in the research pipeline. This leaves laymen wondering how this may impact the beef supply one day.
In light of this, a National Cattlemen’s Beef Association (NCBA) webinar series titled "New Vaccine Technologies: An Addition to Our Animal Health Toolbox" addressed some common concerns and questions.
Dr. Amelia Woolens of Mississippi State University and Dr. Chris Chase of South Dakota State University explained the differences between traditional vaccines – modified-live (MLV) and killed – versus the up-and-coming mRNA alternative.
“RNA vaccines are an option between a modified-live and killed because RNA in the vaccine induces protein production like a modified-live vaccine,” said Woolens in the webinar. “The immune system responds like it's a real infection. But the RNA vaccine doesn't code for the whole virus, so you don't have a whole virus made that might actually cause problems.”
How mRNA vaccines work
The core purpose of vaccinations is to support the cow's immune system, Woolens stressed. This is accomplished effectively but imperfectly with current products on the market.
MRNA vaccines contain what is called messenger ribonucleic acid. These are present in all living creatures, and they tell the body how to make a protein. The immune system then utilizes the protein to help create a response to it.
“Any time a cow is infected with any kind of bacteria or parasite, that cow is going to get exposed to new RNA,” Woolens said. “Some viruses also contain RNA, for example, bovine viral diarrhea virus [BVD], bovine respiratory syncytial virus [BRSV], rotavirus and coronavirus … When the virus infects the cell … [it] starts to copy RNA to make proteins that will become a new virus.”
Dr. David Verhoeven, an assistant professor of vet microbiology and preventive medicine at Iowa State University, is directing USDA grant-funded research on an mRNA vaccine against BRSV.
In an interview, he explained this results in a similar internal response as with a modified-live vaccine or natural infection. Thus, the cell is tricked into thinking that it actually has a viral infection in comparison to traditional killed vaccines that do not. This can create a pretty robust response, resulting in very high efficacy, which sometimes leads to a broader response.
One of the benefits of mRNA vaccines is that they increase the buildup of vaccine proteins in cells over time and teach the immune system based on conditions that look more like a viral infection, encouraging a strong immune response. MRNA vaccines cannot revert to a pathogenic form or mix with circulating pathogens.
Navigating the challenges
Most Americans have become familiar with the concept of mRNA technology via Moderna's and Pfizer's COVID-19 vaccines.
These are made by modifying base pairs and the two ends of the mRNA, which add stability. They are also expensive to produce and utilize.
"How we avoid a lot of these cost-inhibiting additions is that we use alternative strategies where we use what we call RNA structure," said Verhoeven. "RNA folds back on itself, and the structures can actually simulate those five prime caps and that poly A tail on the ends of the mRNA. We can also put structures in that are protected from being sensed by the cells, as well as making it resistant to being degraded by the cell. When we're doing that, our vaccine becomes much, much more affordable. Our vaccine is about 50 cents – and that's without economy [of] scale."
Another major issue besides cost is thermal stability. If mRNA is not stored at 112ºF below zero, it degrades rapidly. This is impractical. But with certain nanoparticles, there is the potential for mRNA to be stable even at room temperature.
An inevitable hurdle on the road ahead is that mRNA vaccines will need to be cleared by the USDA. There are two general ways this can be done, as discussed by Chase in the webinar. These are either a prescription platform (RxP), which requires a veterinary-client-patient relationship to obtain, or a USDA commercial license, which has fewer restrictions.
“[With commercial licensing] we know it's pure … it's safe, but most importantly, we know that it has some proven efficacy, but the other issue is that these licenses can take some time,” explained Chase. “Compare that to the prescription … the development side of it is much shorter than what it would be with a fully licensed product. They're going to be safe, [but] the efficacy is going to be unproven.”
Part of the approval process from the USDA is to determine a withdrawal period for the RNA vaccines. There cannot be any component of the vaccine found in the animal, and with short lifespans, a short withdrawal time is pertinent.
Current state of mRNA vaccines
There are currently some very minimal uses of mRNA vaccines in the livestock sector, but none have been licensed for use in cattle.
The one licensed mRNA vaccine out there is by Merck, called Sequivity, and is a prescription vaccine for swine. With this vaccine, they run into significant issues with thermal stability and have to keep the product at 112ºF below zero. This means they must quickly go to the farm and inject it.
"There hasn't been any other license or licensure for any other mRNA vaccines yet, because it's very early in production animal research. On top of that, our production costs for the RNA is significantly less because again … we'd not have to use the modified base pairs," explained Verhoeven.
The nanoparticles address issues related to temperature storage and make it a viable option for farms, since maintaining a vaccine at the normal temperature is impractical.
Storage and costs are just the first steps. Efficacy and safety will also need to be addressed for widespread adoption.
The future of cattle vaccinations
Despite the obstacles, Woolens believes there is a real potential for mRNA vaccines on cattle operations in the future.
If approved, she noted it could enable very rapid development of more effective vaccines. Another hurdle is that mRNA vaccines require carrier-made lipids and proteins to ensure an immune response.
“These are similar to adjuvants that are included in currently available vaccines, and figuring out the right carrier can take time and money,” Woolens continued. “But prices of a lot of things go down the more we make them, and we may find that RNA vaccines are cost-effective for use in livestock in the near future.”
The take-home message she left her audience is one of optimism for cattle producers looking to the future.
“Vaccines approved by the USDA are pure, safe, potent and effective. That's been the case for the last 100 years,” she stated, reminding her audience that RNA is present in all living things and it enters the body during natural infections or after vaccination with many types of modified-live vaccines. “During the immune response to infection or vaccination, RNA is broken down by naturally occurring enzymes in the body. … Cattle producers need innovative approaches to provide effective vaccines that can be available in a short time frame.”
