SARS-CoV-2 mRNA vaccine is re-adenylated in vivo, enhancing antigen production and immune response

This article is about a new study that showed the first evidence that therapeutic mRNAs are modified in the human body and continue to produce spike proteins.

The findings are significant, in my opinion, because they may explain the many post-vaccine injuries that occur.

The authors are from several institutions in Poland, namely the International Institute of Molecular and Cell Biology, the University of Warsaw, the ExploRNA Therapeutics, the Institute of Biochemistry and Biophysics, and the Centre of New Technologies.

Brief background

The COVID-19 mRNA vaccine should make the body’s cells produce the spike protein to induce immunity.

After injection, the mRNA shot gets phagocytosed or “eaten” by the immune cells, like the dendritic cells and macrophages, which process the antigens and present them on their surfaces. The immune system recognizes the antigens and consequently develops an immune response.

For that to happen, mRNA therapeutics like the Moderna mRNA-1273 were modified. One modification is the elongation of their poly-A tails.

The poly-A tails are a chain of adenosine nucleotides (A) to stabilize the mRNA, protect it from degradation and stop the spike protein transcription.

The Pfizer Bnt162b2 vaccine has a composite poly(A) tail, with 30 As followed by ten other nucleotides and 70 additional As.

Moderna did not disclose the length of its poly-A tail, but the authors used nanopore direct RNA sequencing to count the As in the mRNA-1273. They found the poly-A tail to be about 100As.

Findings

The study found that the poly-A tail of the mRNA-1273 gets degraded at the injection site. However, the poly-A tail becomes longer (re-adenylated) again.

We intramuscularly delivered mRNA-1273 via an in vivo mouse model to study vaccine mRNA metabolism.

We isolated RNA from the tissues at the injection sites 2, 8, and 24 h post-immunization and observed that vaccine mRNA quickly diminishes from the injection site and is barely detectable after 24 h.

Enhanced Direct RNA Sequencing (eDRS) was conducted for samples where a sufficient amount of vaccine mRNA was detected.

To our surprise, a substantial fraction of mRNA-1273 reads had increased poly(A) length, reaching up to 150-200As.

The mean poly(A) length returned to the initial ~100As 72 h after transfection.

The elongation was made possible by the polymerase enzyme TENT5A. Consequently, the mRNA does not get degraded and continues to provide transcripts to make more SARS-CoV-2 spike proteins. 

Furthermore, the re-adenylation allows the macrophages containing TENT5A to process more antigens, increase the spike protein output, and further enhance the immune response. 

Here, for the first time, we show that macrophages play a critical role and are responsible for antigen production.

Not only are  monocytes/macrophages the major cell populations that take up vaccine mRNA5, but these cells also express TENT5A,
which re-adenylates mRNA-1273, thereby increasing its stability and protein output.

The figure below shows the length of poly-A tails of the mRNA in the Bone Marrow-Derived Macrophages (BMDM) as represented by the red color. Notice that they persist for up to 96 hours.

Sars-Cov-2 Mrna Vaccine Is Re-Adenylated In Vivo, Enhancing Antigen Production And Immune Response
Source: Krawczyk, P Et Al. Sars-Cov-2 Mrna Vaccine Are Re-Adenylated In Vivo, Enhancing Antigen Production And Immune Response

Cellular mRNA re-adenylation also happens in other cells and tissues, like the T helper one and T follicular helper cells, and follicular dendritic cells in the lymph nodes, where the mRNA goes. 

Thus, it can be expected that spike (S) proteins produced by macrophages, either at the site of vaccine inoculation or in the draining lymph nodes (where lipid nanoparticles are transported and captured by macrophages), are endocytosed by lymph nodes resident dendritic cells, resulting in induction of T helper 1 (Th1) and T follicular helper (Tfh) cells, and follicular dendritic cells, resulting in induction of humoral immune response.

According to the authors, this can also happen with the Pfizer BNT162b2 mRNA injection.

Although the data presented were obtained using mRNA-1273, similarity in the mode of action of BNT162b2 indicates a likely role for TENT5A for this vaccine as well.

In summary, the research showed that the lifespan of the COVID mRNA jabs is extended in the human body’s immune cells, allowing it to produce spike proteins continuously.

Comment:

The continuous production of the spike protein, the most toxic part of the SARS-CoV-2, allows persistent stimulation of the immune response to create an environment of chronic inflammation.

13 ways that the SARS-CoV-2 spike protein causes damage

Other studies have shown the persistence of spike proteins.

Another research showed that the mRNA in the COVID jabs could be changed into DNA and be combined with the human gene. I discussed those at

LINE 1 can make spike mRNA become part of the human DNA, and Polymerase Theta can Change RNA to DNA

Evidence of SARS-CoV-2 spike protein in human liver cells has been found, and that can be read at Pfizer COVID shot makes human liver cells produce SARS-CoV-2 spike DNA.

The SARS-CoV-2 spike protein cross-reacts with eleven human proteins to cause autoimmune diseases. Thus the continued presence of the spike protein increases the risk of autoimmune, cardiovascular, and thromboembolic conditions.

  1. The SARS-CoV-2 spike protein can form amyloids seen in lung, blood, and nervous system disorders
  2. COVID shots cause a 25% increase in cardiac arrest and acute coronary syndrome in those under 40 years old
  3. Pfizer and Moderna shots increase all-cause mortality: Denmark study
  4. UK Study of COVID-19 shots and Excess Rates of Guillain-Barré Syndrome
  5. Pfizer BNT162b2 adverse events as of February 28, 2021
  6. Tinnitus, hearing loss, and vertigo after COVID vaccines
  7. Risk-benefit analysis shows a higher risk of COVID vax death than COVID-19 disease for those under 80 years old
  8. Rapid Progression of a Lymphoma following Pfizer booster shot
  9. Higher blood pressure after COVID shots and why it happens
  10. Study shows spike proteins affect cardiac pericytes
  11. Retinal complications after COVID shots
  12. mRNA Vaccination Increases the Risk of Acute Coronary Syndrome

 

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References:

  1. Liudkovska V. TENT5 cytoplasmic noncanonical poly(A) polymerases regulate the innate immune response in animals. SCIENCE ADVANCES. 16 Nov 2022
    Vol 8Issue 46 DOI: 10.1126/sciadv.add9468
  2. What is Poly-A tail?- Definition, Structure, and Function

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