Biontech reprogramms immune system

JollyRoger

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Hi guys,

found an interesting article:

https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v1

It is not peer–reviewed but still very disturbing.


The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2
48 vaccination, while fungi-induced cytokine responses were stronger.

TLR4 is a Ligand of Killer cells for the defense of bacteria; TLR7/8 is for the defense of (other) viruses.

The basically tell us that we are immune against Covid but weaker if it comes to the defense of other pathogens.

We all have to deal with chronic infections so can we expect a relapse?
Especially , if the reprogramming is permanent?

Do I get something wrong?
Maybe someone with a little bit more knowledge can enlighten me...
 

JollyRoger

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Thanks for the response...

Well, they actually dont „come up to the expectation“.
The figures don’t show what seems to be a big suppression; its rather a fluctuation.

I was just afraid because im not good with this stuff and this title caught me immediately.
55C2510D-B11E-4E3E-8AE1-D6C19FA3FF6F.png
 
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pattismith

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Hi guys,

found an interesting article:

https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v1

It is not peer–reviewed but still very disturbing.


The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2
48 vaccination, while fungi-induced cytokine responses were stronger.

TLR4 is a Ligand of Killer cells for the defense of bacteria; TLR7/8 is for the defense of (other) viruses.

The basically tell us that we are immune against Covid but weaker if it comes to the defense of other pathogens.

We all have to deal with chronic infections so can we expect a relapse?
Especially , if the reprogramming is permanent?

Do I get something wrong?
Maybe someone with a little bit more knowledge can enlighten me...

Thank you for this important paper!!

It means to me that following the Pfizer covid vaccine:

-inflammatory response from both virus (TLR7 and TLR8 are inhibited) and bacteria (TLR4 is inhibited) is lowered. (I don't know if it means lower virus or bacteria clearance though)

-inflammation response from fungi is increased.

This explains to me why some ME/CFS patients are improved after this vaccine (those who have chronic activation of their TLR4, TLR7, TLR8).

And it may be that those who feel long time worst after this vaccine have some fungus involved in their ME/CFS.
 

pattismith

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The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses (medrxiv.org)

some extracts

Interestingly, we observed important heterologous effects of BNT162b2 vaccination on IFN-γ production induced by other stimuli as well (Figures S2E, 2F).

BNT162b2 vaccination decreased IFN-γ production upon stimulation with the TLR7/8 agonist R848 (Figure S2F).

In contrast, the IFN-γ production induced by inactivated influenza virus tended to be higher two weeks after the second BNT162b2 vaccination, though the differences did not reach statistical significance.

Besides their effects on specific (adaptive) immune memory, certain vaccines such as Bacillus Calmette-Guérin (BCG) and the measles, mumps, and rubella (MMR) vaccine also induce long term functional reprogramming of cells of the innate immune system. (Netea et al., 2020).

This biological process is also termed trained immunity when it involves increased responsiveness, or innate immune tolerance when it is characterized by decreased cytokine production (Ifrim et al., 2014).

Although these effects have been proven mainly for live attenuated vaccines, we sought to investigate whether the BNT162b2 vaccine might also induce effects on innate immune responses against different viral, bacterial and fungal stimuli.

Surprisingly, the production of the monocyte-derived cytokines TNF-α, IL-1β and IL-1Ra tended to be lower after stimulation of PBMCs from vaccinated individuals with either the standard SARS-CoV-2 strain or heterologous Toll-like receptor ligands (Figures 1 and 2).

TNF-α production (Figure 1B-1G) following stimulation with the TLR7/8 agonist R848 of peripheral blood mononuclear cells from volunteers was significantly decreased after the second vaccination (Figure 1C).

The same trend was observed after stimulation with the TLR3 agonist poly I:C (Figure 1D), although the difference did not reach statistical significance

In contrast, the responses to the fungal pathogen Candida albicans were higher after the first dose of the vaccine (Figure 1G).

The impact of the vaccination on IL-1β production was more limited (Figure 2A-2F), though the response to C. albicans was significantly increased (Figure 2F).

The production of the anti-inflammatory cytokine IL-1Ra (Figure 2G-2L) was reduced in response to bacterial lipopolysaccharide (LPS) and C. albicans after the second vaccination (Figure 2K, 2L), which is another argument for a shift towards stronger inflammatory responses to fungal stimuli after vaccination.

IL-6 responses were similarly decreased, though less pronounced (data not shown).

The induction of tolerance towards stimulation with TLR7/8 (R848) or TLR4 (LPS) ligands by BNT162b2 vaccination may indicate a more balanced inflammatory reaction during infection with SARS-CoV-2, and one could speculate whether such effect may be thus useful to regulate the potential over-inflammation in COVID-19, one of the main causes of death (Tang et al., 196 2020).

On the other hand, inhibition of innate immune responses may diminish anti-viral responses.

Type I interferons also play a central role in the pathogenesis and response against viral infections, including COVID-19 (Hadjadj et al., 2020).

With this in mind, we also assessed the production of IFN-α by immune cells of the volunteers after vaccination.

Although the concentrations of IFN-α were below the detection limit of the assay for most of the stimuli, 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 205 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.
All in all, the vaccine may produce less asymptomatic covid infection + less ill people at the same time...
 
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nerd

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As discussed in other posts (1, 2), there is nothing clearly positive or negative to it. Even the paper itself points out potential positives and negatives, such as the inhibited IFN-α response, which might hinder the antiviral response of the immune system but with less inflammation overall.

The study's authors overstate their results by implying that some cytokines such as TNF-α would be generalizable for immune function overall. This is not the case. A real control would have been a model that measures pathogen load somehow and not only humoral response. The study does not show TLR regulation, even though the authors might state it like that. It shows how much cytokine release is triggered by TLR agonists. So when they find increased or lowered cytokines, it might be due to any element in the intracellular TLR pathways. This is a major limitation of this study because it shows a little of everything, but not everything of anything specific. I would wait for more follow-up studies to hopefully shed some light on the changes in protein expression.

The temporary beneficial effect on CFS/ME patients seems to derive from the temporary humoral immune response to the vaccine primarily. IFN-γ might be one reason. I don't know of any cases who completely recovered after the vaccine. Do you?
 

xena

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I'm feeling remarkably more energetic 2 days after my second dose of the Pfizer vaccine. I felt this starting maybe, 9 hours after I got the vaccine. Can someone explain what the effect on the innate immune system is more simply? I don't really understand but I think this may be what is going on.
 

ljimbo423

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This explains to me why some ME/CFS patients are improved after this vaccine (those who have chronic activation of their TLR4, TLR7, TLR8).

And it may be that those who feel long time worst after this vaccine have some fungus involved in their ME/CFS.
This sure makes a lot of sense to me Patti! This is how I read it too.
 
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