The pathogenetic mechanisms of the mRNA spike protein products

Leading to specific types of harm: an analysis from a Russian author

I started on this journey of the mRNA vaccines primarily with the issues with drug manufacturing and batch problems. Which led to contamination and analytical methodology. But I have also been trying to understand the mechanism of action of these vaccines in the manner in which I understand all drug products.

I want to know the entire pharmacological aspects of this product, the pharmacology, secondary pharmacology,biodistribution, mechanism of action of transfection, intracellular activity and then the final immunological phase. Because these products are really multilayered, I found that understanding the mechanism of action was like peeling back the layers of an onion. This was compounded by the fact that there was little data on COMPARATIVE pharmacology, the basis by which we learn about new therapies. Look at old therapies, how does the new one differ? Pharmacokinetics, onset of action, differing ligands/receptors, specific adverse events etc. But the mRNA products are not like anything else commonly used; the closest was Onpattro (patisaran) an orphan drug used for hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis), a rare life-threatening disease. This is caused by mutations in the TTR gene causing polyneuropathy and cardiomyopathy usually diagnosed in males in the 7th decade.

By studying Onpattro I learned A LOT about the LNPs, biodistribution and the pharmacology of such products.

The Biodistribution/Metabolism/Excretion of the Lipids, Part 3

1. My Conceptual Framework

But we need a way to organize and classify all the information we are finally getting on how these products work. My conceptual framework was based on the idea that these are pro-drugs and that there is a pharmacological phase followed by an immunological phase illustrated by Naasani

My last update on my conceptual framework was a bit messy. But it was basically

1. the LNPs biodistribution and toxicity in the blood and plasma

2. the pharmacological phase including the mechanism of action of the LNPs with respect to transfection, endosomal escape, ribosome translation and effects of contamination

3. the immunological phase which I left to others more knowledgeable than I

The Stages in Understanding the modRNA Jabs

2. Russian scientist Kolevatykh Alekseevna, conducted a thorough analysis (Jan 2024)

Based on a tweet from Vaccine Mole this researcher has provided a similar and perhaps clearer conceptual framework for the pathogenetic mechanisms of the mRNA vaccines. This article is in Russian, and it is not known if she has a research profile or if this is fake or not. However, I believe the framework is a useful one for now. Here is the abstract in English.

3. The Pathogenetic Toxicities of the mRNA Vaccines by M.A. Kolevatykh

This scientist presents the pathogenetic toxicity into 3 distinct categories as well as follows:

A. The CHEMICAL toxicity of the the LNPs

1. what would this include?

   I would say this includes both extracellular toxicity as well as intracellular toxicity.

   1. extracellular toxicity in the blood/plasma includes the

      1. ABC phenomenon

      2. CARPA which is ONLY seen in humans and a pig model so mice models do not describe this

      3. the biocorona and its effects

      4. immunogenicity of the pegylated lipid (IgM and IgG)

      5. inflammation due to its physiochemical properties, size, charge, shape etc see Yuan et al

      6. the “nano” aspects of these nanoparticles which is not well understood and I write about it here

   2. intracellular toxicity within the cell

      1. this gets very tricky and is usually just described as Reactive Oxygen Species (see this article by Yu et al) which is described as highly stressful to the cell. The excess generation ROS may induce an array of physiopathologic outcomes, including genotoxicity, apoptosis, necrosis, inflammation, fibrosis, metaplasia, hypertrophy, and carcinogenesis. Yowza.

      2. maybe you have issues with the LNPs embedding themselves in the cells lipid bilayer? This might be important say in fat cells or the myelin sheath around cells and affect nerve function? Maybe?

      3. then you have upstream and downstream cell signalling and cascades from perturbing the lipid bilayer with transfection nicely laid out by my friend

         Genervter Bürger
         in a serious of substack articles ( see here for the first one, only you’ll need to translate to english but it is worth it.)

      4. this new article regarding the biodistribution of EMPTY LNPs also describes the intracellular toxicity of these lipids on metabolism separate from the ROS type toxicity.

         

      

      

      So even without mRNA for spike protein, these LNPs (from Onpattro) upregulated and downregulated metabolic processes. What does repeated injections of these LNPs do to intracellular processes? This fits in with what

      Genervter Bürger
      describes. This also means that these are not excipients, from a regulatory perspective and that the LNPs are NOT a plug-and-play type of platform.

B. The Direct toxicity of the spike protein EXPRESSION (or the pharmacological phase)

In this category we can include all the residual DNA issues and the SV40 issues as well as the mRNA in the LNPs transfecting the cell membrane, being released into the cytosol and then being translated in the ribosome to the spike protein.

1. the effects of contamination of the mRNA which is transfected across the cell membrane with

   1. dsDNA

   2. SV40

   3. dsRNA and other similar contaminants

   4. endotoxin

2. ribosomal frameshifting, stop codon readthrough and ribosomal pausing resulting in aberrant proteins of all kinds from the N-1-methylpseudouridine

3. the 5' cap designed to compete for preferential access to ribosomal complex/reducing translational capacity of other critical proteins (IMPORTANT!!!!), cause NETs forming clotting (thanks Pierre!)

4. the effects of truncated mRNA in the cell

5. endosomal escapse and lysosomal toxicity resembling lysosomal storage disorders

6. up and down regulation of proteins by mRNA with the LNPs in the cell (as shown by the new Nature Biotechnology paper)

   

   How long does this perturbation in metabolic processes last? What adverse events arise from this?

7. What else? Anyone?

C. Destructive effects of the immune response to the spike protein

OK, here is where I have not done a lot of reading except that spike protein fragments are presented on the cell surface which causes the immune system to attack and destroy the cell. However, from a pharmacological perspective, the paper by Kammerer et al showed that the MAJORITY of the spike protein is extruded as EXOSOMES and not on the cell surface. And a lot of spike protein stays INSIDE the cell; only a small amount is actually on the outside of the cell. What this means I don’t know.

Well this needs more work and I will leave this to another day.

4. The Harmful Effects of the Spike Protein Vaccines

Putting together all of the mechanisms of the pathology of these vaccines, Kolevatykh proposes 7 major types of harm.

1. “adhesion” disease defined as below

2. cardiovascular system disorders

3. immune disorders

4. neurological disorders

5. oncogenicity

6. direct toxicity of the LNPs

7. direct toxicity of the mRNA vaccine in the cell, before spike protein is made, and possibly the spike protein itself in the cytosol.

I do not think anyone is surprised by these proposed classification of adverse events. Each of which can be traced back to those overall mechanisms of harm or due to a combination of same.

I think we are getting closer to peeling the layers and having a conceptual framework for harms that can provide a biological rationale for mRNA jab induced injury so that docs can start thinking about HOW this happens. This will hopefully lead to better treatment options etc.

Summary

1. a new paper proposes a conceptual framework for the pathogenetic harms of the vaccine

2. This framework includes the LNPs (extra and intracellularly), then the pharmacological phase (direct toxicity of spike expression) followed by the immunological phase (immune response to the spike protein)

3. From this framework, then major classes of vaccine induced injury can be classified and possibly predicted

4. The hope is that this will lead to a better understanding of the harms of these products and thus better treatments and cures

Comments and discussion welcome

Thanks for reading, and as always Pray the Rosary