In this series, “Promise or Peril: Alarming COVID-19 mRNA Vaccine Issues,” we look at how the introduction of mRNA technology lacked an adequate regulatory framework, paving the way for three major problems: 1) insufficient safety testing of lipid nanoparticles, 2) serious adverse events related to the spike protein, and 3) residual DNA- and lipid-related impurities, as well as truncated/modified mRNA species.
Previously, in Part 1, we discussed how the FDA relaxed the rules for mRNA vaccines compared to mRNA therapies, as well as the available data on lipid nanoparticle (LNP) distribution throughout the body based on animal testing, the lack of human testing, and the lack of mRNA or spike protein biodistribution data. Parts 2 and 3 looked at how LNPs are made, how they behave in the body, and how they might affect health. Part 4 went into greater detail about the spike protein and its subunits’ potential inflammatory and clotting effects.
Part 5 addresses the third major issue associated with DNA contamination caused by residual bacterial plasmids and truncated mRNA from the manufacturing process. Is it possible that vaccines are more contaminated than our regulatory agencies realize? Should this cause concern about cell migration to the gut or cell expression?
The questions posed throughout this series highlight the inherent safety concerns associated with the COVID-19 mRNA vaccines’ approval under a lax regulatory framework. In this article, we look at how lax regulation affects DNA and RNA contamination.
Summary of Key Facts
- DNA contamination in the mRNA COVID-19 vaccines has been a source of concern. The presence of higher-than-expected residual DNA plasmids used in the original mRNA production is of particular concern. According to independent investigations, the Pfizer mRNA vaccine may contain high levels of DNA contamination, potentially exceeding regulatory limits.
- Theoretical risks are associated with plasmid DNA expression and migration to the gut, which could have an impact on human health and the microbiome. Concerns have also been expressed about the quality control and manufacturing oversight of mRNA vaccines.
- The presence of truncated and modified RNA as impurities in the mRNA COVID-19 vaccines was noted by the European Medicines Agency (EMA), Europe’s drug regulatory authority, raising the need for oversight.
In relation to the manufacturing process, a Danish study found a correlation between the rate of adverse events and batch size (number of doses in a batch).
- Last week, the Advisory Committee on Immunization Practices met to recommend the revised COVID-19 vaccine. (pdf) However, the manufacturers presented very little data from human testing. Moderna was the only manufacturer to present data on safety and antibody response from 101 individuals. Pfizer presented antibody response data from 20 mice and is currently collecting data from 400 clinically tested individuals. During the meeting, no data on manufacturing oversight was presented.
- The CMC process (chemistry, manufacturing, and controls) becomes critical in identifying and eliminating impurities as part of the safety evaluation of drug approval. It establishes stringent standards and product specifications to ensure the purity of each batch. Compliance with these standards is required in order to receive approval from global health authorities.
Assume you enjoy coffee and decide to purchase a bag of premium, freshly ground coffee beans from your favorite store. You anticipate that each bag will contain only pure, high-quality coffee grounds for brewing the perfect cup of coffee. When you open the bag, however, you discover that it contains more than just coffee grounds; it also contains sand and other foreign particles. This unexpected impurity ruins your experience completely.
The pharmaceutical industry, including vaccine production, has regulations in place to ensure good manufacturing practices, just as you rely on the purity of your coffee grounds for a great cup of coffee. Patients and consumers anticipate that these guidelines will ensure that drug and vaccine formulations are free of unwanted substances, ensuring their safety and effectiveness.
Controlling impurities in traditional chemical products is a well-established practice, but managing impurities in biological products such as mRNA-based vaccines presents unique challenges.
mRNA Products Contain ‘Gene Factories’
The mRNA in the COVID-19 vaccines is created using double-stranded DNA (dsDNA). Tiny dsDNA plasmids are tiny gene factories (Figure 1). These factories create the mRNA strands found in LNPs. A plasmid resembles a tiny micro-bracelet, with different segments representing various gene segments.
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The number of plasmids in the final lots distributed for injection is limited by regulatory agencies such as the European Medicines Agency (EMA). New questions have been raised about the extent of contamination and whether the FDA is keeping track of it. It is also unknown whether the plasmids can bind to human genes within the cell or travel to the gut.
The EMA standard for vial DNA contamination is 0.33 percent (330 pg/mg), or approximately one DNA molecule for every 3,000 mRNA molecules. Although the Moderna mRNA-1273 vaccine meets this standard, due to poor quality control, the actual volume may be higher. Before distribution, the DNA must be removed from the final product, but some residual amount is expected. The following questions remain unanswered: How much DNA is in the vials? Is it over the top? Is the FDA keeping an eye on this? And, if any, what are the implications for the recipient’s persistence?
At least two independent groups of investigators have conducted lab tests and confirmed that Pfizer’s mRNA vaccine was contaminated with DNA.
A team of scientists led by microbiologist Kevin McKernan published a preprint paper demonstrating that the DNA in the Pfizer/BioNTech BNT162b2 vaccine is “orders of magnitude higher than the EMA’s limit.” His paper hasn’t been peer-reviewed yet. The batches examined were unopened, expired vials that were not delivered on dry ice, according to an anonymous source. If these findings are correct, the actual number of plasmids was 18 to 70 times greater than the EMA limit. (Page 12, Table 3)
Clearly, future research should attempt to determine contamination levels using unexpired doses with an intact cold chain.
Professor Phillip Buckhaults of the University of South Carolina, who holds a doctorate in biochemistry and molecular biology and is regarded as an expert in cancer genomics research, conducted an independent analysis for the presence of DNA in Pfizer batches.
In his testimony, Professor Buckhaults stated:
“The Pfizer vaccine has plasmid DNA contamination.” It isn’t just mRNA. It contains DNA fragments. This DNA is the DNA vector that was used as a template for the mRNA in vitro transcription reaction. I know this because I sequenced it in my own laboratory.”
We will continue to pursue this line of inquiry.
Theoretical Risk of Plasmid DNA Contamination
While the presence of some DNA in a sample is unavoidable and considered acceptable, some have expressed concern about the possibility of genomic integration of the DNA. Because our cells use DNA in the nucleus to make protein, there is a theoretical risk that the plasmid DNA will be transcribed and produce a protein if it enters the nucleus.
An estimated 5% to 10% of our human genome contains ancient retroviral DNA. However, this DNA has been mutated to the point where it is no longer harmful. Any future research on this topic will thus need to establish not only the presence, but also the biological activity of DNA plasmid integration.
In his testimony, Professor Buckhaults added:
“I am kind of alarmed about the possible consequences of this—both in terms of human health and biology—but you should be alarmed about the regulatory process that allowed it to get there.”
Concerns About DNA Migration to the Gut
Concerns about residual expression vectors, or plasmids, in the vials are related to the DNA contamination. More than a kilogram of DNA is required to produce a billion doses of mRNA vaccine. Plasmids assist in the production of DNA by splicing the desired sequence into a bacterial plasmid (Figure 1).
Then workhorse bacteria, usually E. coli, assist in spinning out the DNA for production. These bacteria must replicate not only their own genome, but also the plasmid DNA inserted within their genome. This takes a little longer, so bacteria without the extra DNA will eventually outcompete those with the DNA.
To address this issue, scientists inserted an antibiotic resistance gene. After that, the entire pool of bacteria is treated with an antibiotic to kill the faster-replicating bacteria without conferring antibiotic resistance. This selective elimination allows the antibiotic-resistant bacteria carrying the plasmid to continue growing. In other words, this antibiotic resistance gene confers a benefit that causes selection pressure to favor bacteria that produce the desired DNA.
Some scientists, however, are concerned that exceeding EMA standards for DNA plasmid contamination will have an impact on an already growing antibiotic resistance problem. Only if plasmids containing the antibiotic resistance gene migrate to the gut, integrate with bacterial targets in the gut flora, and disrupt the gut microbiome would this be a potential concern. Obesity, diabetes, cardiovascular disease, cancer, hypertension, and irritable bowel syndrome have all been linked to disruptions in the gut microbiome.
Truncated mRNA Contamination
Since February 2021, the EMA has been monitoring nucleic acid contamination with truncated, or shortened, mRNA fragments. The EMA states on page 35 of its assessment report (pdf) on the BNT162b2 mRNA vaccine reviewed in Part 1 that “truncated and modified RNA are present as impurities.” The impurities were discovered at various levels during production, according to the agency. Levels, for example, may be higher in smaller test batches than in larger commercial batches.
In fact, Max Schmeling, Vibeke Manniche, and Peter Riis Hansen of Denmark linked adverse events with vaccination records and discovered that smaller batches of the BNT162b2 mRNA vaccine may have a higher rate of adverse events (AEs). While this finding is intriguing, the authors urge further investigation to determine whether it is a consistent pattern. We reviewed the raw data provided by the authors and agree that there appears to be a clustering of AEs in batches with fewer than 100,000 doses.
In a laboratory experiment, it has already been demonstrated that mRNA can be reverse-transcribed to DNA in six hours. One unanswered question is whether this can occur in a living organism. So far, there is no evidence that a reverse-transcribed DNA product can merge with the genome of a human cell. Integration claims are purely speculative and are based on an evolutionary precedent for such a process.
The EMA requested additional testing but approved distribution. These fragments were thought to be unlikely to be intact mRNA fragments by the scientists. A cap and a tail are required for an intact mRNA fragment. The cap and tail are required to communicate to the cell when to begin and stop producing the spike protein.
Nonetheless, the EMA requested more reports. The agency was concerned that if the fragments’ potentially encoded proteins resembled human proteins, an autoimmune reaction would be triggered. In other words, if the fragments “mimic” human proteins, antibodies against our own bodies could be developed.
“Any homology between translated proteins (other than the intended spike protein) and human proteins that may cause an autoimmune process due to molecular mimicry should be investigated.” The deadline is July 20, 2021. Interim reports will be issued in March 2021, and monthly thereafter,” the EMA stated.
It is obvious that industrial-scale mRNA production is fraught with danger. Other researchers have recently raised this issue, emphasizing the importance of manufacturing quality control. The Epoch Times, for example, has previously investigated the relationship between quality issues and clotting risk (Part 1, Part 2, and Part 4).
The issue of contamination by DNA and mRNA fragments should be investigated further to determine whether certain lots were more affected than others. We also need to know if DNA contamination is linked to negative outcomes. The EMA must strictly adhere to its monitoring standards.
Given that mRNA is transcribed from DNA vectors, any DNA contamination is biologically unavoidable. The unusually high level of DNA contamination in mRNA vaccines could be a problem here.
However, in the context of a lagging regulatory framework, pivoting these RNA therapeutics to a vaccine platform has left us with many unanswered questions. Nonetheless, public health officials were adamant that this new product be deployed in a one-size-fits-all manner, ignoring different COVID-19 risk profiles across a large population. We believe that this, in turn, set the stage for policy overreach, resulting in unethical and harmful mandates.
Part 1: FDA Oversight Required for New Vaccines and mRNA Therapies
Part 2: The Health Consequences of Poor COVID-19 mRNA Testing: Miscarriage, Vision Loss, and Immunotoxicity
Part 3: Lifting the Veil: mRNA Lipid Nanoparticle Design Created Potential for Clotting and Immune Overdrive
Part 4: A Deeper Look at Spike Protein’s Role in Myocarditis and Blood Clotting Following COVID-19 Vaccination
Part 6 will look at whether the FDA should have relaxed mRNA vaccine regulations during the pandemic, as well as the safety implications of regulatory delays.
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