Vaccines and the innate and adaptive immune systems

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This is my first stab at learning about vaccines. How exactly they work, what do the "adjuvants" do?

Reference:

"Stabilising the Code" by Dr.Mike Williams, UKCOLUMN, 12th September 2021

"Impact of Polymer-TLR-7/8 Agonist (Adjuvant) Morphology on the Potency and Mechanism of CD8 T Cell Induction", Geoffrey M Lynn et al., Biomacromolecules. 2019 Feb 11;20(2):854-870.

In a nutshell - modification of the mRNA (nucleoside uridine code) in covid vaccine acts similar to  adjuvants (in other vaccines) weakening the innate immune system in order to give the chance for the adaptive immune system to activate, recognize and store the pathogen's signature.

That explains why vaccinating against a specific pathogen may make one vulnerable (for a time) to some secondary "opportunistic" infections. Or cancer...

Quotes:

In 2005, Drs. Weissman and Kariko discovered a way to protect foreign mRNA from the body’s immune system. That scientific milestone would be key to the advancement of the mRNA vaccines in 2020.

Recently, the University of Pennsylvania Tweeted a picture of the Drs. Weissman and Kariko receiving their Covid vaccination, and reminding us of that milestone. One tweet commenting that they should receive the Nobel prize for their discovery.

The fundamental change discovered by Weissman and Kariko was that nucleoside modification could protect mRNA from the body’s immune defences:

[picture]

Their key discovery, that by modifying the RNA code (modifying the nucleoside uridine), resulted in ablating the innate immune response, involved toll-like receptors (TLR).

This discovery was adopted in the mRNA technology used in Covid vaccines, in order that the foreign vaccine mRNA could enter cells without being destroyed.
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By modifying the Uridine in the Pfizer vaccine mRNA code, the foreign mRNA is able to bypass part of the body’s first line of defence — the Innate Immune System.

The body possesses two broad parts to its immune system: innate and specific. The innate is the first to go into action against foreign invaders, including foreign mRNA from a vaccine.

How does that simple removal of one letter of code from mRNA achieve that? It does so by affecting Toll Like Receptors (TLR): the alarm signal of the Innate Immune System.

The key TLRs affected are TLR 3, TLR 7 and TLR 8. They act as sentries, whose job is to recognise foreign invaders by way of their form or patterns;
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Dominguez-Andres et al addressed that question May 6th 2021. They state: ...

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BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination.
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We observed a significant reduction in the production if IFN-α secreted after stimulation with poly I:C and R848 after the administration of the second dose of the vaccine (Figure 1H, 1I). This may hamper the initial innate immune response against the virus, as defects in TLR7 have been shown to result in and increased susceptibility to COVID-19 in young males (Van Der Made et al., 2020). These results collectively demonstrate that the effects of the BNT162b2 vaccine go beyond the adaptive immune system and can also modulate innate immune responses.

Three concerns are raised by the above.

1. The ability of the immune system to fight viruses has been diminished; specifically, the ability to fight SARS-CoV-2 may be affected;
2. Vaccine-induced innate immune tolerance may affect other vaccines; and finally
3. What other parts of the immune system may be affected.

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Dr Ryan Cole, a Pathologist, in a recent presentation, stated that he is observing a 20 x uptick in endometrial cancer, and increases in other cancers post SARS-CoV-2 vaccination.
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The toll-like receptors 7 & 8 are described in the literature as important in eliciting the vital CD8 T cell response. With that in mind, let us remind ourselves what Drs. Weissman and Kariko wrote in 2005 in Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA:

We show that RNA signals through human TLR3, TLR7, and TLR8, but incorporation of modified nucleosides m5C, m6A, m5U, s2U, or pseudouridine ablates activity.

That very technology is being used in SARS-CoV-2 vaccines: It switches off TLR 7 & 8 signalling, that the immune system needs to fight infection and cancer.

Summary

Changes to key parts of the mRNA code in SARS-CoV-2 vaccines may be causal in changing the innate immune response via toll-like receptors. Toll-like receptors are important components in defence against infection and downstream effects may also include inhibition of CD8 T cell response. CD8 is a vital part of the immune system’s ability to eradicate infection and cancer. Those changes may be reflected in recent reactivated Varicella Zoster infections although specific mechanisms are unclear at the moment. Anecdotal reports of significant uptick in cancer presenting to medical consultants may be consistent with aberrant toll-like receptor and dendritic cell changes leading to an inhibition of the anti-cancer CD8 effector response. Further data are required but the prospect of an altered CD8 response to infection and cancer is very concerning and should prompt urgent investigation.
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Updated 2-Oct-2021

Another issue to investigate is cytokine storm and ADE (Anti-body Dependent Enhancement)

See the references in: "Mechanism behind rona virus damage"