1. Is mRNA technology an existential threat to animal and human life? Read the Open Letter of Concern and you decide ...

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Open Letter of Concern

The video presentation above is a simplified overview of the scientific and fully referenced Open Letter of Concern below. It is intended for those less scientifically minded, or as a preview to get an overall feel of the topic prior to reading the full Open Letter of Concern. It is based on the Simplified Overview pdf document located on this page that will open a new window to be read or downloaded.

Date: 27th July 2023

To:

1.      Dr Christine Middlemiss BVMS, M.R.C.V.S., Chief Veterinary Officer at DEFRA & VMD

2.      Abigail Seager, Director and CEO, VMD

3.      Gavin Hall, Deputy CEO and Director of Authorisations, VMD

4.      Julia Drown, non-executive Director VMD

5.      Timothy Riley, non-executive Director VMD

6.      Philippa Hardwick, non-executive Director VMD

7.      David Catlow, M.R.C.V.S., non-executive Director VMD

Background

Following the authorisation of the first veterinary "mRNA particle" type "vaccine" - Sequivity for pigs in the USA, it is reasonable to expect that Merck/MSD Animal Health will seek authorisation for it in the UK if they aren’t doing so already. The paper mRNA Vaccine Development for Emerging Animal and Zoonotic Diseases1 published in the Viruses Journal in February 2022 indicates the general intention to develop further mRNA gene therapy products in a variety of different animal species.

Given the announcement of a partnership between Bayer and BioNTech announced in 2016 with the declared aim to produce veterinary mRNA gene therapies2, we must assume that it is only a matter of time before one or more products are presented to the Veterinary Medicine Directive (VMD) for authorisation.

There has also been mention of swapping current animal vaccinations to this mRNA technology. We find it interesting that it is only now when the novel mRNA technology is being pushed that so many weaknesses in current vaccination modalities are revealed in the mRNA Vaccine Development1 paper, and yet the narrative and justification for mass vaccination of our animals has always been how safe and efficacious they are.

The first report of the successful use of in vitro transcribed (IVT) mRNA in animals was published in 19903. Since then, biotech companies had poor results testing mRNA drugs for cardiovascular, metabolic, and renal diseases, cancer, and rare diseases, with most finding that the adverse side-effects of mRNA insertion were too serious. Concern with severe adverse reactions of mRNA vaccines is reflected in the history of vaccine development. This was the very reason for many companies to abandon their development efforts. To now contemplate fast-tracking equivalent products within 8-12 weeks as happens with Sequivity, without long term safety testing and monitoring, is reckless at best.

Firstly, mRNA products of the type referred to as vaccines are nothing of the sort. As recognised by BioNTech in their official SEC filing (bottom of p.14), the FDA regards these mRNA products as gene therapies. Changing the definition of what a vaccine is to include these mRNA products does not make them vaccines, especially when the FDA definition of a gene therapy has not altered to exclude them.  We can only assume that this change in the definition of a vaccine occurred in order to facilitate and fast-track authorisation of these novel products in order to bypass the usual trials and safety net required for non-vaccines because there is sufficient evidence to understand that these mRNA products are potentially inherently unsafe, such that they should only be licensed for use in individual life-saving situations where a congenital genetic disorder exists that so significantly shortens and/or impairs the quality of life that giving gene therapy is worth any risk that the gene therapy represents.

For the reasons set out below, to introduce such novel technologies into animals, especially those destined for the human food chain, exposes meat consumers to a variety of known dangers. This includes humans, our pet carnivores, and captive carnivores in zoos, laboratories etc and wild animals that have access to farmed meat products.

mRNA Technology Inherent Dangers

1.      Lipid nanoparticles:

Lipid nanoparticles (LNPs) used for mRNA products are highly inflammatory. They activate multiple inflammatory pathways and induce IL-1b and IL-6. The LNPs’ inflammatory properties stem from their ionizable lipid component. LNPs may have been responsible for some of the adverse reaction events experience by some people post COVID mRNA injections.4

LNPs can cause blood vessel blockage with subsequent pathologies that can arise from embolism. The lipids used to make LNPs can clump together and have short-lived shelf-life due to storage and temperature requirements. Some of these lipids have a positive charge on them (the ionizable lipid itself), and sometimes the LNP itself can have a positive overall net charge (zeta potential). If the overall net charge on the entire particle itself is positive (less negatively charged mRNA) in the presence of more cationic protonated, positively charged lipids, and some of the entire LNPs can have a negative zeta potential (higher presence of negatively charged mRNA due to the negative charge on the phosphodiester backbone of the mRNA compared to the positive charge of the ionizable lipids), then flocculation will occur when the positive and negatively charged lipids become attracted to one another.5,6

Another way clumping can occur is called the Ostwald ripening effect.7

It is one thing to predict the result of injecting LNPs of known lipid structure (a proportion of which can clump), but altogether a different proposition to inject LNPs that have deteriorated and have altered structures which can happen during both the freezing and defrosting processes, and could result in an exaggerated already highly inflammatory response and/or aneurysm.

2.      mRNA sequelae

When the COVID mRNA products were first launched, much was claimed by the manufacturers that was later subsequently proven to be physiologically and scientifically inaccurate.

a.       The injected product stayed at the injection site: In reality, it was distributed all around the body with differing proclivity in different tissues as anybody with knowledge of the pharmacokinetics of any other injectable products would naturally expect. This included passing through the blood brain barrier. Given the size differential between a whole wild pathogen and snippets of its mRNA and/or a single protein on a capsid it should be no surprise that mRNA products and whatever protein they cause to be produced will go where the pathogen they’re derived from cannot go8,9.

b.      The mRNA stays in the cell cytoplasm: In reality, it was found to be able to enter the nucleus as evidenced by c.

c.       The mRNA cannot alter the recipient’s DNA and genome: In reality, it was found that mRNA can insert into the recipient genome by the action of reverse transcriptase and retrotransposons.10, 11, 12 Once reversed into the recipient genome there is no data to establish what impact this may have on surrounding genes, epigenetic effects, or what risk might result from subsequent mutation.

d.      Because mRNA naturally occurs in the body, it will be recognised and treated as if endogenously produced mRNA. In reality, the mRNA products used pseudouridine that very rarely naturally occurs, and the body does not recognise and respond to it in the same way as uridine. In effect there is no control on how much protein is manufactured by the body, unlike conventional vaccines where there is a known and finite amount of antigen in a dose. Different cells in different organs may respond to the same sequence of mRNA and/or the protein it manufactures in totally different ways.

e.      The quality of mRNA in the products is crucial for their activity: This was why initial stringent cold temperature requirements were in place for product storage and distribution. The inability to adequately quality control the products resulted in the acceptable content level of intended mRNA to be dropped to 55%, and the temperature controls for transport and storage were considerably relaxed.

3.      MicroRNA (miRNA) effects

MicroRNAs are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression13.

The action and role of miRNA is far from being completely understood. By 2018, the miRbase catalogues contained nearly 49000 mature miRNA’s from 271 organisms, this number continues to grow each year. Nonetheless, what we do know about the few that we have limited understanding about, indicates that cell physiology is very sensitive to their presence both qualitatively and quantitively14.

The inability to properly control the quality of mRNA products to date that resulted in the bar being lowered to only 55% of material having to correspond to what was supposed to be present, means that there is a high likelihood that mRNA products will contain snippets short enough to be considered miRNAs, with adverse events being associated with COVID-19 vaccination and dysregulation of endogenous miRNAs15. There is a high probability that random sequences may have variable physiological activity in the body ranging from nothing to serious interference. Given that the mRNA product itself is distributed all around the body we must assume that any miRNA present will be similarly distributed.  We also don’t know how much if any of the mRNA injected is broken down into short enough sections that could have miRNA activity wherever that degradation process takes place.

Interference of vital miRNA cell signalling pathways and controls that we don’t fully understand has the potential to cause serious harms.

4.      Prionogenic Risk

The UK has a history of experience with prion introduction to our food chain with Bovine Spongiform Encephalopathy (BSE) following changes to the rules governing the rendering of material used in making cattle feed in the 1990s.  Certain batches of feed seemed to carry greater risk of resulting in BSE which indicates that the prevalence of BSE in the national herd was ultimately determined by the number of cattle that ate the higher risk batches. Unfortunately, there was a risk to humans from eating beef from affected animals that resulted in nvCJD16,17. The clinical presentation of nvCJD is associated with emergent amyloidosis in major organ systems, and this prionergic mechanism of disease is now considered to be a unifying mechanism underlying proteinopathies associated with multiple neurodegenerative conditions18. Current state of the art understanding with respect to how prions are formed has identified the role of viral peptides that trigger prionergic/amyloidogenic/proteinopathic cascades19,20.

The spike protein of SARS-CoV-2 has been shown to be highly amyloidogenic21. Recent data suggests that mRNA products have an ability to initiate protein misfolding, leading to detectable amyloidogenic signals using PET imaging or as case presentations of systemic amyloidosis22,23. There is evidence suggestive that even mRNA itself can have prionergic activity24. Given the widespread use of vaccinations in all species within the human food chain, and our poor understanding of the prionergic/amyloidogenic potential of any expression products from mRNA constructed to mimic peptides of concern, we would be looking at a widespread (close to 100% in some species) exposure to amyloid and prion disease that could in theory be passed onto consumers, whether human or animals.

Professor Luc Montagnier and others reported a number of confirmed prion diseases in humans following COVID mRNA product injections25, and neurological symptoms have accounted for a high proportion of the more serious adverse reactions reported internationally26. Whether these are all the result of SARS-CoV2 spike protein production, other general risk factors associated with mRNA technology itself, or a mixture of both, is currently unknown. Could this be the result of newly generated miRNA activity or imbalances for example? The answer is that nobody knows because adequate safety studies weren’t and still haven’t been undertaken.  Many individuals within the control group in the original mRNA COVID studies have now been “vaccinated” prior to trial completion, so that this data is now forever invalidated for long term follow-up.

The use of pseudouridine and codon optimisation practises may also alter the secondary structure of the protein produced such that even if the viral/bacterial protein it is supposedly copying is known not to be prionogenic, there is no indication as to the safety of the actual protein manufactured under the direction of the mRNA in the products. If any of these prionogenic scenarios happened to be present, then the adverse effects would be amplified to yet a higher level in the case of self-amplifying RNA products (saRNAs).

In the case of Sequivity, the current authorisation in the USA can only correspond to the process of mRNA product manufacture, and not a defined end product. According to the Sequivity website, a novel mRNA product is generated based on swabs taken from a number of infected pigs on an individual farm. Having sequenced the viral strain genome and a “gene of interest” (GOI) chosen, no doubt corresponding to a superficial viral protein that the immune system can target, a corresponding mRNA sequence is generated, multiplied, and harvested before being sent to the farm for inoculation into the pigs.  The process is claimed to be safe, yet on an individual product basis there is no safety data available given that it takes 8-12 weeks from swab to injection on the farm. Absence of data showing harm because insufficient time has passed to adequately trial a product does not equate to it being safe, or efficacious! Past “success” with one such mRNA product has no bearing at all on the likelihood of success with another mRNA products based on a totally different GOI and protein.

The description of the process of generating an mRNA product has a number of fundamental flaws, not counting the miRNA, quality control, LNPs etc mentioned thus far. Codon coding for amino acids is not an exact process itself. Some amino acids have multiple possible codons, and some triplet codons can code for more than one amino acid. The “wrong” sequence of amino acids can fundamentally alter the spatial folding of the end protein, which could turn out to be prionogenic.

The product data submitted for Sequivity authorisation in the USA14 has an adverse reaction table at the very end on page 18 where death is the 2nd most common adverse reaction at 3.2%. We must assume that this was the best figure available for submission, but it has no predictive value for any other mRNA product other than the exact same one used in the trial that was submitted.

Given that protein misfolding and resulting prion diseases can take years to manifest clinical symptoms, we cannot take the risk that years down the road we suddenly find increases in nvCJD, amyloidosis or similar in people that has been contracted from eating contaminated meat. Eating meat from animals that haven’t manifested any symptoms of prion disease prior to slaughter doesn’t preclude the possibility that meat from these individuals can contain prionogenic misfolded proteins. When there is no safe level of prion15, it is the role of the Veterinary Medicines Directive in the UK to protect both animals and consumers from this possibility.

5.      Immunity considerations

Whilst the papers that are advocating mRNA product use in animals are strongly positively in favour, they focus so much on pointing out that the antibody response is stronger/better than conventional vaccines that they fail to consider that the ideology behind vaccination was to use a mild transient adverse response in order to prevent severe disease in the few individuals that might have contracted it. Instead, the new mRNA products seem to be inducing a stronger response that could arguably be considered to impact more individuals more severely than the disease itself might cause. We are at risk of promoting a medicine that is worse than the disease simply because it’s a new technology that is being portrayed as more advanced.

There are no long-term studies to ascertain the long term immune response and degree of protection, or what multiple mRNA product administration might cause either for multiple different diseases and/or repeat injections of the same product or similar variant. The 8-12 weeks used to produce a new version of Sequivity cannot possibly ascertain whether the protein chosen to be produced is prionogenic or if sufficiently close in structure to a naturally occurring protein in the recipient, it might set off an autoimmune disorder. What is the point of producing a very strong beneficial immune response against a pathogen if it initiates adverse disorders of greater magnitude in the process?

If the human mRNA COVID products are anything to go by, animal products might reduce the risk of severe disease in the very short term, but over time detrain and supress the immune response through increased IgG427 such that the more injections are given the greater the risk of contracting infection. Whether this is peculiar to Coronaviruses that have a history of Antibody Dependent Enhancement with past conventional vaccines, or whether this might be something that all mRNA products risk causing is unclear because there are insufficient long-term studies other than those prior to COVID where manufacturers withdrew from going to market due to safety concerns.

If it were not for the waiver of liability, manufacturers of the mRNA products granted temporary authorisation for COVID did not have the confidence in the safety of their products to allow distribution with manufacturer liability, as evidenced by their refusal to supply those countries who refused to waive liability. That in itself reveals everything we need to know about the inherent safety of mRNA products.

Conclusion

In short, introduction of exogenous RNA risks interference in fundamental processes that we know insufficient about without long term studies. Whilst we cannot categorically say that the potential risks detailed above will definitely occur, there is absolutely no evidence to categorically say they won't, and that the mRNA products are safe either.

No doubt the VMD will come under pressure to authorise novel mRNA products in food animals and for pets too in the UK. We, the undersigned urge caution and consider that there is currently more evidence to confirm that it is imperative that the usual long term studies are completed in full without shortcuts than evidence to suggest that these products are safe.

Signed…

Roger S. Meacock BVSc., M.R.C.V.S.

Dr Kevin McCairn Ph.D

R. M. Thornsberry D.V.M., M.B.A., Chairman Animal Health Committee, R-CALF-USA

Dr Siguna Mueller, Ph.D, Ph.D

References
  1. Le, T., Sun, C., Chang, J., Zhang, G. & Yin, X. mRNA Vaccine Development for Emerging Animal and Zoonotic Diseases. Viruses 14 (2022). https://doi.org:10.3390/v14020401
  2. News, G. E. B. Bayer Partners with BioNTech to Develop mRNA Vaccines, Drugs for Animal Health, <https://www.genengnews.com/topics/drug-discovery/bayer-partners-with-biontech-to-develop-mrna-vaccines-drugs-for-animal-health/> (2023).
  3. Wolff, J. A. et al. Direct gene transfer into mouse muscle in vivo. Science 247, 1465-1468 (1990). https://doi.org:10.1126/science.1690918
  4. Ndeupen, S. et al. The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. iScience 24, 103479 (2021). https://doi.org:10.1016/j.isci.2021.103479
  5. Kulkarni, J. A. et al. On the Formation and Morphology of Lipid Nanoparticles Containing Ionizable Cationic Lipids and siRNA. ACS Nano 12, 4787-4795 (2018). https://doi.org:10.1021/acsnano.8b01516
  6. Faizullin, D., Valiullina, Y., Salnikov, V. & Zuev, Y. Direct interaction of fibrinogen with lipid microparticles modulates clotting kinetics and clot structure. Nanomedicine 23, 102098 (2020). https://doi.org:10.1016/j.nano.2019.102098
  7. Gindy, M. E. et al. Stabilization of Ostwald ripening in low molecular weight amino lipid nanoparticles for systemic delivery of siRNA therapeutics. Mol Pharm 11, 4143-4153 (2014). https://doi.org:10.1021/mp500367k
  8. Merian, J. et al. Comparative biodistribution in mice of cyanine dyes loaded in lipid nanoparticles. Eur J Pharm Biopharm 93, 1-10 (2015). https://doi.org:10.1016/j.ejpb.2015.03.019
  9. Merian, J. et al. Synthetic lipid nanoparticles targeting steroid organs. J Nucl Med 54, 1996-2003 (2013). https://doi.org:10.2967/jnumed.113.121657
  10. Domazet-Loso, T. mRNA Vaccines: Why Is the Biology of Retroposition Ignored? Genes (Basel) 13 (2022). https://doi.org:10.3390/genes13050719
  11. Doerfler, W. Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based Covid-19 Vaccines: Possible Integration into the Human Genome - Are Adenoviral Genes Expressed in Vector-based Vaccines? Virus Res 302, 198466 (2021). https://doi.org:10.1016/j.virusres.2021.198466
  12. Sattar, S. et al. Nuclear translocation of spike mRNA and protein is a novel feature of SARS-CoV-2. Front Microbiol 14, 1073789 (2023). https://doi.org:10.3389/fmicb.2023.1073789
  13. Yeo, J. H. & Chong, M. M. Many routes to a micro RNA. IUBMB Life 63, 972-978 (2011). https://doi.org:10.1002/iub.524
  14. Kozomara, A., Birgaoanu, M. & Griffiths-Jones, S. miRBase: from microRNA sequences to function. Nucleic Acids Research 47, D155-D162 (2018). https://doi.org:10.1093/nar/gky1141
  15. Miyashita, Y. et al. Circulating extracellular vesicle microRNAs associated with adverse reactions, proinflammatory cytokine, and antibody production after COVID-19 vaccination. npj Vaccines 7, 16 (2022). https://doi.org:10.1038/s41541-022-00439-3
  16. Wells, G. A. et al. A novel progressive spongiform encephalopathy in cattle. Vet Rec 121, 419-420 (1987). https://doi.org:10.1136/vr.121.18.419
  17. Bruce, M. E. et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 389, 498-501 (1997). https://doi.org:10.1038/39057
  18. Goedert, M. NEURODEGENERATION. Alzheimer's and Parkinson's diseases: The prion concept in relation to assembled Abeta, tau, and alpha-synuclein. Science 349, 1255555 (2015). https://doi.org:10.1126/science.1255555
  19. Tetz, G. & Tetz, V. Prion-like Domains in Eukaryotic Viruses. Scientific Reports 8, 8931 (2018). https://doi.org:10.1038/s41598-018-27256-w
  20. Woerman, A. L. & Tamgüney, G. Body-first Parkinson’s disease and variant Creutzfeldt–Jakob disease – similar or different? Neurobiology of Disease 164, 105625 (2022). https://doi.org:https://doi.org/10.1016/j.nbd.2022.105625
  21. Nystrom, S. & Hammarstrom, P. Amyloidogenesis of SARS-CoV-2 Spike Protein. J Am Chem Soc 144, 8945-8950 (2022). https://doi.org:10.1021/jacs.2c03925
  22. Laudicella, R. et al. Subcutaneous Uptake on [18F]Florbetaben PET/CT: a Case Report of Possible Amyloid-Beta Immune-Reactivity After COVID-19 Vaccination. SN Comprehensive Clinical Medicine 3, 2626-2628 (2021). https://doi.org:10.1007/s42399-021-01058-0
  23. Leung, W.-Y., Wu, H. H. L., Floyd, L., Ponnusamy, A. & Chinnadurai, R. COVID-19 Infection and Vaccination and Its Relation to Amyloidosis: What Do We Know Currently? Vaccines 11, 1139 (2023).
  24. Kovachev, P. S. et al. RNA modulates aggregation of the recombinant mammalian prion protein by direct interaction. Sci Rep 9, 12406 (2019). https://doi.org:10.1038/s41598-019-48883-x
  25. Perez, J.-C., Moret-Chalmin, C. & Montagnier, L. Emergence of a New Creutzfeldt-Jakob Disease: 26 Cases of the Human Version of Mad-Cow Disease, Days After a COVID-19 Injection. International Journal of Vaccine Theory, Practice, and Research 3, 727-770 (2023). https://doi.org:10.56098/ijvtpr.v3i1.66
  26. Hosseini, R. & Askari, N. A review of neurological side effects of COVID-19 vaccination. European Journal of Medical Research 28, 102 (2023). https://doi.org:10.1186/s40001-023-00992-0
  27. Irrgang, P. et al. Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination. Sci Immunol 8, eade2798 (2023). https://doi.org:10.1126/sciimmunol.ade2798


Signatories

If you are a veterinary surgeon, veterinary organisation, scientist or person of influence who would like your signature added to the above Open Letter of Concern, and/or if you have additional information that you think should be included, please email here

This subject is relevant to every country. If you would like to use this Letter of Concern to put your veterinary medicines regulator on notice then please contact Roger using the email link above so we can coordinate our efforts.


The Veterinary Medicines Directive Reply

Received 17.08.2023

VMD reply

The pdf document reply to the above Open Letter of Concern would appear to be a bog standard reply template as suggested by the reply document title along with the single stock jpg signature on behalf of all addressees. The reply is only addressed to one of the original two co-signatories and omits Dr Kevin McCairn. It is suggestive that little attention was paid to the overall concerns, let alone the details and references included in the Open Letter of Concern.

Nonetheless, the VMD have undertaken to abide by their duty to ensure that animal and human health is properly safeguarded and to not authorise any veterinary medicinal products that compromise either. The VMD are now on notice and are duty-bound by their own words to ensure all our concerns are addressed by any trial data submitted within an authorisation application.

If/when they authorise an mRNA veterinary medicinal product for animal use in the UK, we can then ask for the submitted trial information in order to assess whether there has been sufficient testing, and whether sufficient time has passed post administration of any product to check the product safety in relation to all the concerns we have drawn attention to in the Open Letter of Concern.

If we consider that our concerns are not satisfied by the trial data, then rest assured we will hold the VMD to account for whatever failures the authorisation procedure reveals.


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Open Letter
Simplified Overview

For those who are less scientifically orientated, below is a downloadable pdf which is a simplified overview of the full Open Letter of Concern.

Simplified pdf version of Open Letter of Concern

Supporting information
Dr Alexandra Henrion Caude warning about interfering with RNA in 2020.

A much longer and more recent presentation can be viewed here.


Christie Grace on LNPs
Christie Grace on LNPs

Christie Grace is a specialist in RNA and lipid nanoparticles and was a project manager at the top plasmid company in the world manufacturing recombinant proteins such as monoclonal antibodies, CRISPR, SpCas9, gene editing, and IVT mRNA production.

For two years Christie has been raising the alarm over harms that can be caused by lipid nanoparticles and has concerns over cold chain management, vaccine production quality assurance/control and the medical community's unwillingness to look at the scientific data.


Dr Segalla on LNP Toxicity

Dr. Gabriele Segalla, Independent Research Biochemist, Specialist in Chemistry of microemulsions and colloidal systems, author of scientific publications and holder of various international patents, examines significant aspects of the chemical-physical criticalities and toxicological potential of an mRNA vaccine.


Codon Optimisation

How codon optimisation impacts the mRNA and the protein synthesised.


mRNA Vaccine Toxicity
by Michael Palmer MD

This book explains the inherent dangers of mRNA technology and is available as a free download from D4CE.org