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mRNA Vaccines Explained

Guest post by Whyser

What Is mRNA?

mRNA stands for messenger RNA (ribonucleic acid, a nucleic acid present in all living cells). RNA’s principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins, although in some viruses RNA rather than DNA carries the genetic information.

Coronavirus is a single-stranded RNA virus. The RNA is its genetic blueprint which exists inside of a protein shell like membrane covered in spike proteins which function like a “key” searching for a “lock”. Once inside your body, the virus looks for cells that have an ACE2 receptor, in order for it to gain entry into a cell. The binding of the protein and receptor allows for entry, where the virus releases its genetic material inside the cell, take over the machinery of the cell to make copies of itself, and multiply.

Interestingly, in a study of 300 people, children ages 4-9 were found to have lower expression of ACE2 receptors than all older age groups studied, which could explain why children are at lower risk of infection.

How Does the mRNA Vaccine Work?

Now that you have an idea what mRNA is, the vaccine is utilizing the same machinery of the virus. The mRNA vaccines have strands of genetic material encapsulated inside a man-made lipid shell. That synthetic coating protects the mRNA from enzymes in the body that would otherwise break it down. The coating is also irritating enough to enables the mRNA to enter the dendritic cells and macrophages in the lymph node near the vaccination site.

mRNA material provides instructions for the cell make a piece of the “spike protein” unique to SARS-CoV-2, which is then displayed on the cell’s surface, signaling the immune system to begin producing antibodies and activating T-cells to fight off what it thinks is an infection.

Learn about COVID Vaccine Ingredients and Vaccine Reactions to the COVID Vaccine.

There are three major pathways for an mRNA vaccine to stimulate an immune response:

1. mRNA itself is considered a Pathogen Associated Molecular Pattern (PAMP)

The immune system responds to two things, damage associated and pathogen associated molecular patterns (DAMP and PAMP respectively). Vaccines typically work by causing DAMP (by killing cells in our body with adjuvants).

On the other hand, our immune system also can detect conserved or previously memorized patterns (PAMP) that it inherently knows is bad. mRNA detected outside the cell is considered bad because it indicates one of two things: a cell died, or that it’s a virus.So mRNA, the very instruction set that needs to get inside our immune cells (those are the target cells that the vaccine is trying to infect with mRNA), is also an immunostimulatory factor.

2. Polyethyline Glycol (PEG) infused in Lipid Nanoparticles

Because mRNA is so unstable (which is why Pfizer’s vaccine requires extreme cold storage to remain stable), one way to make it more stable is to envelope the mRNA in a lipid layer. If you are familiar with lyphospheric vitamin C, this is a very similar concept, to envelope vitamin C in a lipid sphere in order to increase cellular uptake and bioavailability. The same holds true for mRNA.

The lipid layer in some mRNA vaccines (I’m not certain of which ones), can be infused with polyethyline glycol, which would act as the adjuvant.I know PEG has gotten a bad rap, but it also serves other purposes, like preventing the lipid envelope from binding to other proteins in our bodies, and to allow the mRNA to escape the envelope after it bypasses the cellular wall.

Our bodies tend to form anti-PEG antibodies when exposed to it. The lipid layer can also contain other pro-inflammatory factors that would stimulate a Th1 response.

3. The lipid envelope contains or the mRNA encodes for proinflammatory precursors

Since the lipid envelope contains the mRNA payload, the envelope may contain other proinflammatory factors in order to start an immune response. The other way is for the mRNA itself to encode for proinflammatory precursors so that the cell starts producing them along with the COVID protein.

How Can mRNA Vaccines Cause Autoimmunity?

In the case of mRNA vaccines, the invocation of Th1 (cell mediated response) may lead to increased risk of autoimmunity. A cell mediated response would typically destroy an infected cell, thereby destroying the viruses that have infected it. The destruction of a cell can release a lot of human substances in an already inflammatory environment, which can accidentally make the immune system mistakenly think that some of the cell components are the bad guys.

If this isn’t balanced out properly with Th2 (humoral/antibody response), and the ability to tell the immune system to regulate itself (turn off the inflammatory response), it can lead to an increase in autoimmunity risk.

What About Asymptomatic Transmission?

The vaccines may lessen symptoms and are not proven to prevent transmission. While that seems like a great idea, there is still a danger with that. People with mild symptoms or asymptomatic may assume that they are not sick. People who don’t think that they are all that sick are less likely to restrict themselves and therefore have a higher potential to go out into the public and unknowingly spread the disease to those who didn’t get vaccinated, or those who couldn’t.

On the same token, these people are also less likely to get tested to see if they have COVID and it will make tracking the number of cases more and more difficult.

This is part of the same reason why pertussis cases fluctuate so much.

Can the COVID Vaccines Cause Infertility?

I think the concern is that the mRNA that encodes for the spike protein in coronavirus may be structurally similar to fertility hormone syncytin-1. If that is true, there may be some cross reactivity (aka the immune system doesn’t know the difference between them, so it may end up attacking both).

Why Were Previous Attempts at SARS Vaccines Unsuccessful?

All SARS/COVID vaccine attempts since the early SARS pandemic in the early 2000s never made it to market.

Why?

Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1716185/

Although any reduction in SARS-CoV titer can be interpreted as a positive aspect of a potential vaccine, given the relationship between viral titer and SARS disease severity, the increased number of lymphocytic and eosinophilic inflammatory infiltrates, which are also characteristic of the immune pathology observed with respiratory syncytial virus (RSV) infection following vaccination with formalin-inactivated RSV, raises concerns that vaccination with N alone will not only fail to effectively protect against SARS-CoV replication, but may result in vaccine-enhanced pulmonary disease

Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035421

This effort was hampered by the occurrence in the initial preclinical trial of an immunopathogenic-type lung disease among ferrets and Cynomolgus monkeys given a whole virus vaccine adjuvanted with alum and challenged with infectious SARS-CoV [14]. That lung disease exhibited the characteristics of a Th2-type immunopathology with eosinophils in the lung sections suggesting hypersensitivity that was reminiscent of the descriptions of the Th2-type immunopathologic reaction in young children given an inactivated RSV vaccine and subsequently infected with naturally-occurring RSV [32]–[33]. Most of these children experienced severe disease with infection that led to a high frequency of hospitalizations; two children died from the infection [33], [40], [41]. The conclusion from that experience was clear; RSV lung disease was enhanced by the prior vaccination

Basically what happens in a challenge test is the following:

1) Get vaccinated with SARS/COVID vaccine

2) Wait for antibodies to be generated

3) Expose subject to natural SARS/COVID virus (this is the challenge)

4) See if subject is protected or gets worse

As indicated in the studies above, the vaccine never made to market because those who were challenged suffered from pulmonary immunopathy (severe lung inflammation) that was WORSE than getting COVID.

Challenge testing has never been tested in the current batch of vaccine attempts.

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