Dr. Smith

Specific concerns about the use of ModRNA vaccines in Farming

Veterinary modRNA Vaccines Are Being Fast-Tracked for Rollouts
One Health: Vaccinating Animals to Protect the Health of People

The concept of ‘one health’ is that the health of people, animals, and the environment are interlinked and interdependent. The health of one can potentially impact the health of the other two.

For example, the most potentially dangerous forms of the ‘flu’ occur when human influenza viruses exchange chunks of genetic material with influenza viruses that infect pigs and birds. This can result in outbreaks in the human population of swine and avian flus. There are many other zoonotic pathogens that can be transmitted from animals to people. As such, there is growing interest in promoting global human health through the mass vaccination of animals of agricultural interest. The rationale is that if animals can’t get a disease and transmit the causative agent to people, this could avoid outbreaks in the human population.

One Health: Fast-Tracking of Veterinary modRNA Vaccines

Many modRNA vaccines are being developed with the goal of administering these to food producing animals. Historically, the first clinical testing of a mRNA vaccine was in cattle, preceding the rollout of COVID-19 modRNA vaccines into people. Australia is currently an example of a country in which new modRNA vaccines against Foot and Mouth Disease and Lumpy Skin Disease are being fast

tracked to address the economic impact of these diseases on their livestock industry17. The same is occurring for a wide array of other pathogens, including influenza viruses in poultry and swine18.

Why Should People Care About modRNA Vaccines for Farm Use?

There are at least six reasons:

1. If veterinary modRNA vaccines targeting pathogens that can infect people are as far from meeting the definition of an ideal vaccine as the COVID-19 vaccines were, then massive numbers of animals will be conferred with far from sterilizing immunity. This, in turn, could produce massive reservoirs of animals around the world that can promote the emergence of unique and potentially immuno-evasive variants of zoonotic pathogens that could then infect people. Global regulators should be compelled to insist, without compromise, that veterinary modRNA vaccines for zoonotic pathogens confer immunity, which the modRNA vaccines that are currently available for people fail to confer. This means that animals receiving vaccines should be rendered unsusceptible to the target disease, and they should be unable to transmit the causative agent to others, especially humans. Unlike COVID-19 modRNA vaccines, veterinary modRNA vaccines should be required to undergo formal transmission testing as part of any approval process.

2. COVID-19 modRNA ‘vaccines’ are injected into muscles, then they distribute throughout the body, and can leave the body as evidenced by their secretion in breastmilk. This means there is the potential for modRNA vaccines to get into edible tissues of food animals. It would not be safe, nor medically approved, for people to consume veterinary modRNA vaccines in milk, eggs, and meat. Careful testing needs to be done to determine where modRNAs and other components or derivatives from modRNA vaccines go in the bodies of animals and how long they last in veterinary species. This would determine, in part, the ‘wash-out’ period, which is how long one needs to wait before obtaining food from agricultural species to ensure humans are not exposed to the medical product.
17 htps://www.abc.net.au/news/rural/2022-08-22/foot-mouth-vaccine-development-fast-tracked-nswbiosecurity/101356300 (accessed March 2, 2024)
18 Rcheulishvili N, Papukashvili D, Liu C, Ji Y, He Y, Wang PG. Promising strategy for developing mRNA-based universal influenza virus vaccine for human popula on, poultry, and pigs- focus on the bigger picture. Front Immunol. 2022 Oct 17;13:1025884. doi: 10.3389/fimmu.2022.1025884. PMID: 36325349; PMCID: PMC9618703.

3. Wherever modRNA can be found in an animal’s body, one would also expect there to be the protein that it encodes. This represents a major concern for modRNA vaccines for farming. The potential problem here is a phenomenon known as ‘oral tolerance’19. Immune systems are designed to interpret things that are eaten as being non-dangerous. This is to avoid harmful chronic inflammation in the gastrointestinal tract (stomach and intestines), as well as food allergies. It also prevents suffering chronic inflammation against the massive number of bacteria and viruses that live in the gastrointestinal tract. When people eat something, their immune systems become unable to respond to it20. The goal of using modRNA vaccines in food animals to try to stop zoonotic pathogens before they can infect people could backfire badly if the proteins from pathogens get into animal-derived food products. Inducing oral tolerance against pathogen-derived proteins could cripple a person’s ability to protect themselves against the pathogen being targeted.

4. The concept of ‘GMO foods’ (GMO = genetically modified organism) is already a substantial hurdle in the agricultural industry for many consumers. Use of modRNA vaccines would render animals at least transiently genetically modified (assuming the synthetic RNAs are eventually cleared). But, until scientifically proven otherwise, there even remains the possibility of permanent genetic modification of animals. This could occur should any modRNA get reverse transcribed into DNA and integrated into an animal’s chromosomes. Alternatively, there is the consistent contamination of COVID-19 modRNA vaccines with bacterial DNA used to manufacture the modRNA. With genetic components like the SV40 promoter in the DNA contaminating Pfizer/BioNTech’s modRNA vaccine, there exists an alternative potential mechanism whereby there could be permanent integration into the chromosomes of cells. Any of these possibilities could add a novel wrinkle to the concept of GMO foods and needs to be closely evaluated through research, with the goal of adopting suitable regulatory policies.

5. Ther is also the well-being of farm animals that needs to be considered, especially if an array of different modRNA vaccines end up being administered, with the potential for each of them requiring repeated dosing. Modified RNA vaccines are not entirely safe in people, especially if more than one dose is administered, and this may apply to animals as well. Care must be taken to ensure that animal welfare is preserved, along with their ability to reproduce efficiently. Research in animals represents an ideal scenario to conduct extensive and careful studies into the safety of modRNA vaccine technologies, including addressing the numerous legitimate, well rationalized safety questions that have been raised but largely ignored during the rollout into humans.
19 Rezende RM, Weiner HL. Oral tolerance: an updated review. Immunol Let. 2022 May;245:29-37. doi: 10.1016/j.imlet.2022.03.007. Epub 2022 Apr 5. PMID: 35395272.
20 Yoshida T, Hachimura S, Kaminogawa S. The oral administra on of low-dose an gen induces ac va on followed by toleriza on, while high-dose an gen induces tolerance without ac va on. Clin Immunol Immunopathol. 1997 Mar;82(3):207-15. doi: 10.1006/clin.1996.4319. PMID: 9073543.

6. Research is being conducted to get plant-based foods to produce modRNAs for consumption by people. For example, there is a project at the National Science Foundation, California, United States of America, in which lettuce and spinach are being engineered to express proteins from pathogens by giving these plants modRNA genetic blueprints.21 The idea is that people will eat these plants, and this will induce an immune response that, in theory, could protect them from a targeted disease. Here are key quotes from the report:

a) “Ideally, a single plant would produce enough mRNA to vaccinate a single person”
b) “We are testing this approach with spinach and lettuce and have long-term goals of people growing it in their own gardens”
c) “Farmers could also eventually grow entire fields of it.”

Again, this would represent a novel form of GMO food. The risk of modRNA vaccines or their components/derivatives getting into food derived from agricultural animals would likely be an unintended harm by those trying to protect animal and human health. But turning edible plants into modRNA vaccine factories is intended to get people to consume the proteins encoded by the modRNA genetic blueprints. This concept of food-packaged pathogenic proteins converts the theoretical risk of consumption with food animals into a blunt reality. Once again, this raises the potential for unintended oral induction of immunological tolerance against pathogens.

Indeed, scientists have been using this precise strategy of expressing target proteins in plants to harness the power of oral tolerance to cripple the immune system in a way that would prevent it from causing “autoimmune, allergic and inflammatory diseases”22. This means that eating parts of pathogens in the context of food products could backfire. The intention would be to induce protective immune responses. However, the overall weight of the scientific literature suggests that the most logical hypothesis is that it will render the immune system less able to respond to pathogens. Further, controlling dosing with these kinds of vaccines would be impossible, especially if people were to grow them in their gardens. First, the amount of target protein that is manufactured from modRNAs is already inherently unpredictable; it depends on the metabolic activity of the cells that randomly acquire the modRNAs. Further, people could consume as much modRNA as they wish should it be grown in edible plants. There would be no ability for health professionals to provide oversight for the consumption of such vaccines. The ability to regulate the administration of vaccines would be lost. Also, the messaging with COVID19 modRNA vaccines was that ‘more is better’. For some people, this approach could drive massive consumption home grown modRNA vaccines. Some people don’t understand that ‘more’ does not equal ‘better protection’ when it comes to vaccines; and overdosing could be harmful. A vaccine requires a target protein(s) plus an adjuvant, which provides a danger signal to the immune system, so it knows to respond to the target. It is unknown how lettuce and spinach, which people consume regularly, would be perceived as dangerous by the immune system. One of the two main ingredients in the recipe for an ideal vaccine seems to be missing.
21 htps://www.universityofcalifornia.edu/news/grow-and-eat-your-own-vaccines (accessed March 2, 2024)
22 Ma S, Liao YC, Jevnikar AM. Induc on of Oral Tolerance with Transgenic Plants Expressing An gens for Preven on/Treatment of Autoimmune, Allergic and Inflammatory Diseases. Curr Pharm Biotechnol. 2015;16(11):1002-11. doi: 10.2174/1389201016666150826121334. PMID: 26306744.

If foodborne pathogen-derived proteins were somehow able to induce an aggressive immune response against a pathogen, one must wonder if there could be a risk of this breaking tolerance to other protein components of the food. If this was to occur, it could lead to the induction of food allergies. Projects like this raise the concern of whether they are being conducted merely to push technological boundaries in the absence of involvement of immunologists trained in vaccinology. Technological innovations do not automatically translate into good for the world. In my expert opinion, getting people to eat food expressing proteins from pathogens could be a recipe for rendering large numbers of people more susceptible to the very diseases that researchers would be aiming to protect against.

Author: Dr Byram Bridle, is an Associate Professor of Viral Immunology who specializes in the subdiscipline of vaccinology.