Treize
Member
One of the reasons why mRNA vaccines, and other genetic vaccines such as the ones using DNA delivered by a viral vector, seem to cause so many side effects seems to be the way these work. I.e. these side effects are a self-fulfilling prophesy.
In order to get a proper picture we need to look at both cell biology and the immune system first.
A virus is - supposedly - a bit of genetic material contained in a shell of (mainly) proteins. These proteins latch on to certain receptors on cells, allowing the virus to enter the cell. Inside the cell the genetic payload is delivered and - long story short - hijacks the cell's protein production process to make copies of itself. So, a virus inserts genetic material into your cell that gets translated into proteins by your own ribosomes. Feel free to correct me if I am wrong.
The adaptive immune system, that vaccines try to influence, works by antigen presenting cells ('APC's') finding antigen proteins in the body and bringing those over to the lymph node. In the lymph node the APC's who picked up an antigen "present" them to T helper cells, which in turn activate B cells and cytotoxic T cells. B cells produce antibodies, i.e. proteins that latch on to viral proteins preventing cell entry. Cytotoxic T cells detect and kill infected cells. The way cytotoxic T cells detect infected cells is due to the fact cells use a sort of signaling system to show what proteins they are producting. When they are infected, the produce viral proteins. In order for this sigalling system to work, some of the proteins being produced are broken up into preptides, mounted on a "MHC 1 receptor" and displayed on the cell's surface.
If we take a protein based vaccine, one injects the patient with antigen proteins. These get picked up by APC's and this triggers the immune system. To get enough APC's to the injection city they usually use an adjuvant. Adjuvants can cause side effects too, but that's another topic.
These gentech platforms are designed to act like a virus, in the sense that they bring foreign genetical material into your cells in order for your ribosomes to produce the desired protein. The pharma guys are now able to achieve this. However, the mayor problem with this technology is getting the genetic material into the right cells. This problem seems to prevent most use cases for this tech. However, the immune system is present everywhere. So some particulary devious people came up with the idea of using this tech for vaccines, by making your own cells produce the antigen.
Now, when this genetic material be it mRNA contained in a lipid nano particle or DNA contained in an adeno virus, enters into your cell the cell will produce these proteins and display them on the surface. These can interact with APC's as far as I understand. A porting is broken down an displayed through MHC 1. Once the cytotoxic T cells are activated all these cells will be targeted and killed. This results in cell-loss and local inflamation. After cell death the proteins and peptides still in the cell are released, which can further interact with APC's (or cause damage).
We know the J&J and the AZ injections contain 50 billion viruses, the Sputnik one has 100 billion. We do not know how many LNP's are contained in the mRNA vaccines, but I assume it is probably even more. (Also bear in mind the number of LNP's or viruses do not give us a true estimation of the number of cells "sacrificed", as cells can repackage mRNA into exosomes which can enter other cells).
In short, genetic vaccines work by sacrificing up to 100's of billions of cells in your body every dose by triggering an immune response against otherwise healthy cells.
Now, this would perhaps not be a major issue is this happened in your arm. But we now know this junk spreads through the entire body.
Mostly accumulating in the liver, but also entering the blood stream and entering the heart muscle cells, the brain (!) and other organs.
It seems pretty obvious all the side effects we are seeing are caused by this issue. It is not something unexpected either.
Both Pfizer and Moderna do not use lipid particle formulations that give it some type of cell or organ targetting ability. You will find zero thought given to this issue in papers published by these companies. The only Western mRNA company that seems to be given this some thought is Arcturus, but they are very vague about it.
(From my understanding an mRNA based vaccine would be most safe if it enters APC's directly.)
However, some interesting studies have appeared on PubMed the last few years which seem to provide evidence for the fact the pharma crooks recognise that "biodistibution" of the mRNA is liked to side-effects.
A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity - PubMed : This article concerns a proposed c00f vaccine using a lipopolyplex platform instead of LNP's.
"While a variety of delivery systems for mRNA vaccine have been developed, there are still concerns regarding unfavorable biodistribution pattern due to their unique size and composition, (...) In an effort to circumvent these issues, we applied a core–shell structured lipopolyplex (LPP) platform for mRNA vaccine production. (...) Since the LPP particle resembles the overall structure of a virus, it provides certain advantages such as facilitated cell uptake and stimulation of key signal transduction pathways that are essential for activation and maturation of APCs, such as Toll-like receptor 7/8 signaling. In this study, LPP also showed high transfection efficiency and sustained expression of targeted mRNA molecules in APCs such as DC2.4 cells. Besides, in comparison with traditional LNP, LPP expressed mRNA mostly in injection site after intramuscular inoculation and preferred expressed mRNA in spleen instead of liver after its leakiness in blood vessel, which may alleviate the worry about the potential off target effect and systemic toxicity."
pubmed.ncbi.nlm.nih.gov
"Current messenger RNA (mRNA) vaccines in the clinic were reported to induce side effects in the liver, such as reversible hepatic damages and T cell–dominant immune-mediated hepatitis, which might be caused by the undesired expression of antigens in the liver."
"The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific expression in the LN compared with LNP formulated with ALC-0315, a synthetic lipid used in the COVID-19 vaccine Comirnaty."
More acknowledgement can be found in the following article which specifically covers this issue.
link.springer.com
In any case, anyone here has something to add with regards to the biodistribution issue?
Why is it not considered to be much of an issue, even in pre-covid medicial literature?
Is the idea that all cells producting the spike protein will be killed wrong?
Let me know...
In order to get a proper picture we need to look at both cell biology and the immune system first.
A virus is - supposedly - a bit of genetic material contained in a shell of (mainly) proteins. These proteins latch on to certain receptors on cells, allowing the virus to enter the cell. Inside the cell the genetic payload is delivered and - long story short - hijacks the cell's protein production process to make copies of itself. So, a virus inserts genetic material into your cell that gets translated into proteins by your own ribosomes. Feel free to correct me if I am wrong.
The adaptive immune system, that vaccines try to influence, works by antigen presenting cells ('APC's') finding antigen proteins in the body and bringing those over to the lymph node. In the lymph node the APC's who picked up an antigen "present" them to T helper cells, which in turn activate B cells and cytotoxic T cells. B cells produce antibodies, i.e. proteins that latch on to viral proteins preventing cell entry. Cytotoxic T cells detect and kill infected cells. The way cytotoxic T cells detect infected cells is due to the fact cells use a sort of signaling system to show what proteins they are producting. When they are infected, the produce viral proteins. In order for this sigalling system to work, some of the proteins being produced are broken up into preptides, mounted on a "MHC 1 receptor" and displayed on the cell's surface.
If we take a protein based vaccine, one injects the patient with antigen proteins. These get picked up by APC's and this triggers the immune system. To get enough APC's to the injection city they usually use an adjuvant. Adjuvants can cause side effects too, but that's another topic.
These gentech platforms are designed to act like a virus, in the sense that they bring foreign genetical material into your cells in order for your ribosomes to produce the desired protein. The pharma guys are now able to achieve this. However, the mayor problem with this technology is getting the genetic material into the right cells. This problem seems to prevent most use cases for this tech. However, the immune system is present everywhere. So some particulary devious people came up with the idea of using this tech for vaccines, by making your own cells produce the antigen.
Now, when this genetic material be it mRNA contained in a lipid nano particle or DNA contained in an adeno virus, enters into your cell the cell will produce these proteins and display them on the surface. These can interact with APC's as far as I understand. A porting is broken down an displayed through MHC 1. Once the cytotoxic T cells are activated all these cells will be targeted and killed. This results in cell-loss and local inflamation. After cell death the proteins and peptides still in the cell are released, which can further interact with APC's (or cause damage).
We know the J&J and the AZ injections contain 50 billion viruses, the Sputnik one has 100 billion. We do not know how many LNP's are contained in the mRNA vaccines, but I assume it is probably even more. (Also bear in mind the number of LNP's or viruses do not give us a true estimation of the number of cells "sacrificed", as cells can repackage mRNA into exosomes which can enter other cells).
In short, genetic vaccines work by sacrificing up to 100's of billions of cells in your body every dose by triggering an immune response against otherwise healthy cells.
Now, this would perhaps not be a major issue is this happened in your arm. But we now know this junk spreads through the entire body.
Mostly accumulating in the liver, but also entering the blood stream and entering the heart muscle cells, the brain (!) and other organs.
It seems pretty obvious all the side effects we are seeing are caused by this issue. It is not something unexpected either.
Both Pfizer and Moderna do not use lipid particle formulations that give it some type of cell or organ targetting ability. You will find zero thought given to this issue in papers published by these companies. The only Western mRNA company that seems to be given this some thought is Arcturus, but they are very vague about it.
(From my understanding an mRNA based vaccine would be most safe if it enters APC's directly.)
However, some interesting studies have appeared on PubMed the last few years which seem to provide evidence for the fact the pharma crooks recognise that "biodistibution" of the mRNA is liked to side-effects.
A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity - PubMed : This article concerns a proposed c00f vaccine using a lipopolyplex platform instead of LNP's.
"While a variety of delivery systems for mRNA vaccine have been developed, there are still concerns regarding unfavorable biodistribution pattern due to their unique size and composition, (...) In an effort to circumvent these issues, we applied a core–shell structured lipopolyplex (LPP) platform for mRNA vaccine production. (...) Since the LPP particle resembles the overall structure of a virus, it provides certain advantages such as facilitated cell uptake and stimulation of key signal transduction pathways that are essential for activation and maturation of APCs, such as Toll-like receptor 7/8 signaling. In this study, LPP also showed high transfection efficiency and sustained expression of targeted mRNA molecules in APCs such as DC2.4 cells. Besides, in comparison with traditional LNP, LPP expressed mRNA mostly in injection site after intramuscular inoculation and preferred expressed mRNA in spleen instead of liver after its leakiness in blood vessel, which may alleviate the worry about the potential off target effect and systemic toxicity."
Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8 + T cell response - PubMed
The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored...
pubmed.ncbi.nlm.nih.gov
"Current messenger RNA (mRNA) vaccines in the clinic were reported to induce side effects in the liver, such as reversible hepatic damages and T cell–dominant immune-mediated hepatitis, which might be caused by the undesired expression of antigens in the liver."
"The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific expression in the LN compared with LNP formulated with ALC-0315, a synthetic lipid used in the COVID-19 vaccine Comirnaty."
More acknowledgement can be found in the following article which specifically covers this issue.
Establishing the Pharmacokinetics of Genetic Vaccines is Essential for Maximising their Safety and Efficacy - Clinical Pharmacokinetics
In a typical course of drug development, thorough pharmacokinetic (PK) studies are essential for the determination of drug biodistribution, dosage and efficacy without toxicity. For vaccines, however, unless a new formulation component is used, most regulatory agencies rule out the need for...
In any case, anyone here has something to add with regards to the biodistribution issue?
Why is it not considered to be much of an issue, even in pre-covid medicial literature?
Is the idea that all cells producting the spike protein will be killed wrong?
Let me know...
