Effective vaccines for COVID-19 should have heralded the benefits of mRNA vaccines, but fear and misinformation about their supposed dangers circulated at the same time.
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These misconceptions have recently spilled into worries about whether their use in agricultural animals could expose people to components of the vaccine within meat or milk.
In fact, a number of U.S. states are considering legislation either outlawing the use of mRNA vaccines in food animals or, at minimum, requiring their labelling on animal products in grocery stores.
Idaho introduced a bill that would make it a misdemeanor to administer any type of mRNA vaccine to any person or mammal, including COVID-19 vaccines. A Missouri bill would have required labelling on products derived from animals administered mRNA vaccines, but failed to get out of committee. Arizona and Tennessee have also proposed labelling bills.
I am a researcher who has been making vaccines for years and started studying mRNA vaccines before the pandemic. My research on using mRNA vaccines for cattle respiratory viruses has been referenced by social media users and anti-vaccine activists, who say that using these vaccines in animals will endanger the health of people who eat them.
But these vaccines have been shown to reduce disease on farms and it’s all but impossible for them to end up in your food.
Vaccine background
Farmers have long used several types of vaccines to protect their animals, from inactivated vaccines that contain a killed version of a pathogen to live-attenuated vaccines with a weakened version of the pathogen and subunit vaccines that contain one part of a pathogen.
All can elicit good levels of protection from disease symptoms and infection. Producing these vaccines is often inexpensive. However, each has drawbacks.
Inactivated and subunit vaccines often do not produce a strong enough immune response, and pathogens can quickly mutate into variants. The weakened pathogens in live-attenuated vaccines have the remote possibility of reverting back to their full pathogenic form or mixing with other circulating pathogens and becoming new, vaccine-resistant ones.
They also must be grown in specific cell cultures to produce them, which can be time-consuming.
There are also several pathogens, such as porcine reproductive and respiratory syndrome virus, foot and mouth disease virus, highly pathogenic avian influenza and African swine fever virus, for which all three traditional approaches have yet to yield an effective vaccine.
Another major drawback for all three vaccine types is the time it takes to test and obtain federal approval to use them. Typically, in the U.S., animal vaccines take three or more years from development to being licensed. Should new viruses make it to farms, traditional vaccine development could take too long to contain outbreaks.
The science
All cells use mRNA, which contains the instructions to make the proteins needed to carry out specific functions. The mRNA used in vaccines encodes instructions to make a protein from a pathogen of interest that immune cells learn to recognize and attack.
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This process builds immunological memory, so that when a pathogen carrying that same protein enters the body, the immune system will be ready to mount a quick and strong response.
Compared to traditional vaccines, mRNA vaccines have several advantages that make them ideal against emerging and persistent diseases.
Unlike killed or subunit options, mRNA vaccines increase the buildup of vaccine proteins in cells over time and train the immune system using conditions that look more like a viral infection. Like live-attenuated vaccines, this process fosters development of strong immune responses that may build better protection.
In contrast to live-attenuated viruses, mRNA vaccines cannot revert to a pathogenic form or mix with circulating pathogens. Furthermore, once the genetic sequence of a pathogen of interest is known, mRNA vaccines can be produced quickly.
The mRNA in vaccines can come in either a form that is structurally similar to what is normally found in the body or in a form that is self-amplifying, called saRNA. Because saRNA allows for higher levels of protein synthesis, researchers think that less mRNA would be needed to generate similar levels of immunity.
On the other hand, a COVID-19 saRNA vaccine developed by biopharmaceutical company CureVac showed less protection than traditional mRNA approaches.
Merck’s Sequivity, for swine flu in pigs, is currently the only saRNA vaccine licensed for animals in the U.S. The product is also approved in Canada.
All mRNA vaccines are made using methods developed decades ago. Only recently has the technology advanced to the point where the body doesn’t immediately reject it by activating anti-viral defences intrinsic to each cell. This rejection would occur before the immune system even has the chance to mount a response.
The COVID-19 mRNA vaccines mix in modified nucleotides — the building blocks of RNA — with unmodified nucleotides so the mRNA can hide from those anti-viral sensors. These modified nucleotides are what allow the mRNA to persist in the body’s cells for a few days rather than just a few hours like natural mRNA.
New delivery methods using lipid nanoparticles also ensure the mRNA isn’t degraded before it has a chance to do its job.
Safeguards
Despite this stability, mRNA vaccines do not last long enough within animals for any component of the vaccine to end up on grocery shelves. Unlike for human vaccines, animal vaccine manufacturers must determine the withdrawal period in order to obtain approval in the U.S. This means any component of a vaccine cannot be found in the animal prior to milking or slaughter. Given the short lifespan of some livestock and intense milking schedules, withdrawal periods often need to be short.
Between the mandatory vaccine withdrawal period, flash pasteurization for milk, degradation on the shelf and the cooking process for food products, there could not be any residual vaccine left for humans to consume. Even if you were to consume residual mRNA molecules, your gastrointestinal tract will rapidly degrade them.
The already approved Sequivity does not use the modified nucleotides or lipid nanoparticles that allow vaccine components to circulate longer in the body, so long-term persistence is unlikely.
Several veterinary mRNA vaccines are in early development.
Like in people, animal vaccines are tested for safety and effectiveness in clinical trials. As with all animal vaccines, future mRNA vaccines will also need to be fully cleared from the animal’s body before those animals can enter the food system.
Whether mRNA vaccines will displace other vaccine types for livestock is yet to be determined. The cost of manufacturing these vaccines, logistical challenges (such as their need to be kept very cold and warmed before use to avoid degradation), and the efficacy of different types of mRNA vaccines all need to be addressed before there is large-scale use.
Traditional vaccines for food animals have protected them against many diseases. Limiting the use of mRNA vaccines would mean losing a new way to protect animals from pathogens that current vaccines can’t fend off.
– David Verhoeven is an assistant professor of Vet Microbiology & Preventive Medicine at Iowa State University. This article was originally published at the Manitoba Co-operator and first appeared in the Conversation, by Reuters.
