I think it's this one, published on Nature yesterday (Dec. 6th).
N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting
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From what I understand (I'm retarded tho), the project aimed to reduce the harmfulness of the chain reactions following mRNA-vaccination, or something like that. The unintended immune reactions are part of the background info.
Here is the news report about it from the University of Cambridge website:
https://www.cam.ac.uk/research/news...-prevent-potentially-harmful-immune-responses (
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EDIT - ok I can't find the specific information about unintended immune reactions, this is probably the wrong study.
EDIT 2 - wait they did some trials with mice, maybe that's what they're referring to.
I'd have better luck interpreting my own future out of traditional chinese characters than understanding all the technical jargon in the Nature article so I'm going to stop embarrassing myself now.
You found the correct study, thank you for that.
Ok, I'll give my breakdown of the study. First off, a little nomenclature and mechanism. Ψ in the context of the study is pseudouridine. So 1-methylΨ should be read as 1-methylpseudouridine. The typical bases used for mRNA encoding are adenine (A), cytosine (C), uracil (U), and guanine (G). In mRNA Uracil (U) fills in for the thymine (T) that is used in DNA encoding. In order to stop the immune system from destroying the mRNA right off the bat before it can be useful Pfizer substituted 1-methylΨ (Ψ) for Uracil (U).
mRNA is read in a series of "Frames" also known as Codons. Each frame consists of 3 bases, with each codon encoding for a specific amino acid to be used in protein synthesis (with the exception of the 3 base codes for "Start", "Stop", and a few other special commands). A frameshift is when the frame for which 3 bases get grouped and read together for their 3 base code gets changed. In this instance the type of frameshift they are talking about is when the mRNA reading mechanism sees 1-methylΨ and had trouble reading it since it's not a standard uracil. In most cases the 1-methylΨ looks and acts enough like a normal uracil that the mRNA reading mechanism doesn't really notice that it isn't a proper uracil. But, every so often the mRNA reading mechanism sees the 1-methylΨ and decides its crap. This is an expected behavior for the mRNA reading mechanism. Crap can be randomly inserted into mRNA sequences, or the mRNA could have been created wrong, etc... so this is normal behavior for the mRNA reading mechanism when it sees something other than a normal base in the sequence. When this happens the mRNA reading mechanism will decide what its looking at is crap and in a +1 frameshift will shift the groupings of the bases backwards by 1 when putting together a frame. This is known as a +1 frameshift. This is a serious problem because all the future frames it reads will be wrong. You can think of it like this using the sequence below:
CCAGAΨGGAA
Normally the sequence would be read like this:
CCA GAΨ GGA A...
But with a +1 frameshift we get:
...C CAG AΨG GAA
This won't impact the frame for CCA because its amino acid will already be in place, but the frames beyond that will all be altered, coding for the wrong amino acids and the protein will come out with the wrong sequence of amino acids, being an anomalous protein rather than the intended protein.
I want to stress that this study was done in a test tube and a cell culture for the first part, and mice in the second part. At no point were actual humans used.
According to this study:
"1-methylΨ does not seem to affect codon misreading, but has been shown to affect protein synthesis rates and ribosome density on mRNAs, suggesting a direct effect on mRNA translation"
One of the purposes of this study was to determine if this was indeed true. If it was, we should see normal proteins, even if it is at a reduced rate. If it is incorrect, then we will see normal protein, but we should also see frameshift +1 abnormal proteins in a significant quantity if the 1-methylΨ was actually causing codon misreading.
As can be seen in figure 1, they did get mostly normal protein, but there was a significant quantity of abnormal proteins that would only have occurred if there was a frameshift +1 mutation, proving that 1-methylΨ does indeed create the frameshift +1 reading frame alternation. You can think of this experiment as a "proof of concept" it didn't involve anything having to do with the vaccine, but it was meant to validate their base theory and methodology for determining if 1-methylΨ +1 frameshifting was indeed possible and if it could happen in human cells, and both were proven to be true.
In the next part they used mice to determine if this carried over to actual living mammals, if the abnormal proteins in question were generated by the actual Pfizer mRNA vaccine, and if they were indeed immunogenic, meaning they elicited an immune response. I would like to stress that we make screwed up proteins all the time, it's a matter of statistics that when making so many proteins a certain amount are going to be crap. The body and the immune system have an entire protocol for dealing with screwed up proteins and it is nothing out of the ordinary. It would be far more concerning if the immune system ignored screwed up proteins and allowed them to build up.
In the experiment they were able to prove that the mice when immunized with the Pfizer mRNA vaccine produced the abnormal proteins from the +1 frameshifting due to the 1-methylΨ and the immune system identified it as a foreign protein and destroyed it. They were also able to demonstrate that the immune reaction to the +1 frameshifting protein is not the result of just the COVID-19 spike protein or even just COVID-19 vaccination since mice vaccinated with another COVID-19 vaccine, specifically ChAdOx1, which was not an mRNA vaccine, did not have an immune reaction to the abnormal frameshift +1 protein. This means that the other vaccine, ChAdOx1, which was not an mRNA vaccine did not cause the production of the abnormal protein. while the mice that got the mRNA vaccine did react to the presence of the abnormal protein. This demonstrated that the immune cells from the mice vaccinated with the Pfizer mRNA vaccine had indeed seen the abnormal proteins before as a result of their initial vacciantion.
The next part of the article demonstrates that the mistranslation that created the abnormal protein was indeed from a +1 frameshifting mechanism and not due to another mechanism. You can think of this section as being a double-check to show that what they thought was happening was indeed what happened, and not something else. You usually have to do this in experiments because one of the first things someone will ask after you have proven something is "Well, couldn't it be XYZ instead" and unless you have confirmed it isn't another mechanism, your results will be questionable.
The section after that is them proving that it was the stalling of the translation process caused by 1-methylΨ specifically that leads to the frameshift +1 mistranslation which created the abnormal protein. Again, this is meant to validate their theory in the other direction. That not only was it from +1 frameshifting, but it was specifically from the mechanism they proposed using 1-methylΨ and not something else that could cause +1 frameshifting. This is also typically expected in an experiment because again the first thing someone will ask is "Well, we know its a +1 frameshift, but couldn't that have been caused by ABC instead" and unless you have proven that your mechanism is the most likely explanation, people will question the validity of your results.
In the conclusion they talk about how the study proves that 1-methylΨ in mRNA vaccines causes +1 frameshifting, that the the abnormal protein is created in living mice from the Pfizer mRNA vaccination, and that the immune system of the mice recognize the abnormal protein produced by the Pfizer mRNA vaccine, which could be an issue for future uses of this mRNA technology.
One of the most important take away points from this study is the following:
"Although there is no evidence that frameshifted products in humans generated from BNT162b2 vaccination are associated with adverse outcomes, for future use of mRNA technology it is important that mRNA sequence design is modified to reduce ribosome frameshifting events, as this may limit its future use for applications that require higher doses or more frequent dosing, such as the in vivo production of hormones."
They make a salient point. The less off-target protein that is produced by a vaccination or other medical products using this mRNA technology the better off everyone is since its entirely possible, although extremely unlikely, that a rogue protein could be created if this technology was used in the future for something else and it may not be an innocuous protein such as the abnormal protein produced by this vaccination. I agree. They also propose another method that would work just as well, but would drastically reduce the potential for abnormal protein production. That is obviously something that needs to be investigated further.
For TL;DR people:
1. The experiment was done with test tubes, cells in dishes, and mice, not with people. Any data generated from this experiment has to be extrapolated to human beings. So, this study provides absolutely no information or proof of any harm created by any mRNA vaccination in any human whatsoever.
2. They were able to prove that the Pfizer vaccine did indeed lead to a small, but significant amount of deformed spike protein being generated in mice due to the mechanism they researched. They did demonstrate that this is unique to the Pfizer mRNA vaccine as this immune response was not seen in mice vaccinated with the ChAdOx1 vaccine.
3. The deformed protein was recognized by the mouse immune system and destroyed, just like every other damaged protein in the body. The body has an entire system for getting rid of crap proteins. The mouse immune system attacked and digested the deformed protein exactly like it handled the correct spike protein. There was no evidence that the deformed protein produced any detrimental effect on the mice.
4.
"Although there is no evidence that frameshifted products in humans generated from BNT162b2 vaccination are associated with adverse outcomes, for future use of mRNA technology it is important that mRNA sequence design is modified to reduce ribosome frameshifting events, as this may limit its future use for applications that require higher doses or more frequent dosing, such as the in vivo production of hormones."
This study literally doesn't say anything about human response to the vaccine, or the human immune response to the potentially malformed protein. The article in the OP is 100% complete horseshit. They are attributing something to this study that it never said, and never intended to say. It doesn't even involve humans.
Hopefully my breakdown of the actual study will remind everyone here, again, not to read clickbait garbage and actually think it is worth more than something to read while wiping your arse.
If anything I wrote above is unclear, please feel free to ask, I will do my best to answer any questions.
