The Pseudouridine Question
I think I've discovered why the vaccine wears off. It was never supposed to make you immune to begin with.
I have said before that the reason I’m afraid to take the COVID vaccines is that their mechanism of operation is too much like that of the virus. The only thing that really distinguishes the Pfizer and Moderna mRNA vaccines from the virus - or if you want to get technical, a subviral agent that infects cells like the virus but only makes them produce the spike protein - is the substitution of the uridine in the RNA code with pseudouridine. Or to be more precise, the full name for the nucleotide chemical is N1-methyl-pseudouridine but if you use big science-y words such as that then be prepared for this:
Yes, that’s the type of ignorance that we’re dealing with. Remember that should you ever feel unsure over whether you’re crazy to question whether these are safe. Now if I could just remember where I made that comment thread with that one idiot who read the word “pseudouridine” and thought I was talking about Sudafed…
The whole reason why Dr. Katalin Karikó and her partner Dr. Drew Weissman became so famous during the pandemic (apart from Karikó being a female scientist because feminism) is because of their discovery regarding nucleotide substitutions in RNA. You see, the problem with using RNA as a gene therapy treatment is that the innate immune system, or to be more precise, the toll-like receptors (TLR7 to be specific) inside the cell will recognize it as foreign and cause the cell to react as though it has undergone a viral infection. As it turns out it is specifically the uridine nucleotide (this is the “U” in RNA genetic code; it substitutes for thymine, the “T” in DNA genetic code) that triggers this immune reaction. But if it is substituted with pseudouridine (the Greek letter psi, or “Ψ” is used in place of the “U” to denote such substitions), as it turns out, there will be little or no immune reaction to the foreign RNA, yet it will still function as a normal mRNA and translate into the same protein.
Now this makes sense for a gene therapy. After all, you don’t want the body reacting to the new gene that you insert, but rather to be immunotolerant to it like it is to all the other proteins in your body (barring autoimmune disorders in which case the immune system reacts to what should be self-antigens). However, the purpose of a vaccine is to do the complete opposite - to STIMULATE immunity to the antigen. In fact the presence of normal uridine itself could suffice as an adjuvant for an mRNA-based vaccine. Seeing that it’s absent from both the Pfizer and Moderna brands, however, begs the question of what serves as an adjuvant, or else demands an explanation as to why an adjuvant is not required.
Indeed, I’ve encountered (and regrettably, neglected to screencap) a number of ignorant vaxx zealots who fancy themselves science experts that have answered this question of mine by stating that it’s the uridine that serves as the adjuvant, showing that they are either ignorant of the special function of Weissman & Karikó’s contribution to science, or of the fact that such a modification is being used in these products. Others have told me that the PEG-ylated surface of the lipid nanoparticles is supposed to be the adjuvant, but I don’t find that explanation to be satisfactory, because while a lot of people carry antibodies to PEG (many to the point of being allergic!) there are also a lot of people that don’t, and in fact PEG has often been added to drugs with the intention of REDUCING the immune response, so if that’s the case then it may have an adjuvant effect in some people (mainly just those with a mild allergy to it) but not in everyone, or anywhere even close to everyone, thus rendering it ineffective in a large number of people.
The more intelligent vaxx zealots - the ones that won’t think you’re talking about cooking meth when you name the substituted nucleotides - will tell you that the reason why pseudourylated mRNA has to be used is because the mRNA drug will trigger too severe an immune reaction if normal mRNA is used. (Now if we just used a protein vaccine like Novavax we wouldn’t have to worry about that sort of thing… but too bad, we have to use mRNA because it’s the FUTURE! beep boop boop bop)
Case in point - Curevac, another biotech firm from Germany that specializes in experimental mRNA drugs, made a COVID vaccine candidate that uses regular unsubstituted RNA, but in a very small dose so that it doesn’t cause such a severe immune response. The tolerable dose appears to be too small to be effective however, seeing that the Curevac trials showed less than the 50% efficacy required to qualify for emergency use authorization. Though that might also have something to do with the fact that they didn’t store their formula in a deep freezer.
But even with the pseudouridine substitutions it appears that a lot of people suffer fairly severe adverse effects from these vaccines, at least compared to other vaccines. “ThAt MeAnS iT’s WoRkInG!” the propagandists insist, as though the torturous 18th-19th century practice of “heroic medicine” has made a comeback. (I would be very disturbed if I got a high fever or a severe headache after getting a vaccine - that’s not how MY immune system works!) Still, there are also many who have suffered nothing more severe from these injections than one would expect had they been injected with saline. Is it working for them? Supposedly there is no correlation between antibodies produced and severity of side effects. How about in the long-term? How about T-cell immunity? Are they killer T or regulatory T or both? Are they exhausted T-cells? How is it even making antibodies in the first place?
So the mechanism of action for stimulating immunity as described both in company research papers and on their official websites is vague, and in I can’t get a straight answer from any so-called “experts”, who themselves are likely bluffing, with a psychology similar to that in Hans Christian Anderson’s classic tale “The Emperor’s New Clothes”. The clinical trials themselves seem to have been rushed, and it appears that they have deliberately neglected to test for asymptomatic infections. There are some post-trial studies on asymptomatic transmission, but they are corrupted by the fact that they are not double-blind; the vaccinated group is inherently biased by the different behavioral and medical factors that influence both the odds one will catch COVID in any given time period, and whether one will choose to get vaccinated or not, and even more so early on in the pandemic when these studies were conducted, before incentives, and later, mandates increased the diversity of the vaccinated group. I imagine the early takers skew more educated, risk-averse and White, all factors that reduce the incidence of catching COVID, though education level and race at least may be controlled for. It’s too late to do another double-blind study, as the pool of unvaccinated people in countries with easy access to ultracold freezing technology who for the sake of science are either willing to risk getting injected with the real thing, or not getting injected with the real thing, has been utterly exhausted. The study I looked at wasn’t even peer-reviewed yet, but the scientifically ignorant journalists that work for the mainstream media were promoting it like it was, and it may have been what convinced our scientifically ignorant politicians into thinking that vaccine mandates were justified.
I begin to theorize… suppose this type of vaccine - at least as a long-term effect not immediately noticeable in just the first few months after inoculation - has the effect of tricking your body into thinking that the spike protein is a self-antigen so that your immune system doesn’t attack it. At least in some people, perhaps only those that aren’t allergic to PEG or whatever. This would reduce COVID symptoms that are caused by the immune system attacking your body too hard. But it would also allow the virus to proliferate until it turns every infectible cell in your body into a virus factory, which I imagine could kill you, depending on how long the cell remains a virus factory (the ribosome stops translating the RNA code at some point, which makes the virus self-limiting) and how much it interferes with cellular function. Suppose this happens in some capacity, at least for some period, that the host doesn’t die, but rather becomes an asymptomatic reservoir for the virus, like what happens inside the body of a bat. That would actually make it a selfish decision to get vaccinated! You would be able to go anywhere you want and spread viruses with gleeful abandon without suffering the consequences, and those that don’t want to get vaccinated because they don’t want to risk the possibility of a severe adverse reaction will be forced to get vaccinated thanks to your reckless behavior making it unsafe NOT to be vaccinated. Kind of like how driving over the speed limit could force everyone else to drive over the speed limit just to prevent the others that are driving over the speed limit from crashing into them.
This would explain why the COVID death count in 2021 was higher than the death count in 2020; if we give the propagandists the benefit of the doubt, that the unvaccinated make up the vast majority of the deaths, it still doesn’t add up that their death count would be up when half of their community is vaccinated, if the vaccine is actually reducing transmission, unless some theory can be contrived about there being an uncanny valley in herd immunity such that it goes down before it goes up or something but I haven’t seen that yet and I better not give them any more ideas… this increase in viral transmission must be caused either by the biological effects of the vaccines themselves, or the moral hazard incurred by those that erroneously believe that being vaccinated makes it virtually impossible for them to get infected, enabled by the reopening of businesses, schools, and social venues, if not both. And lest you think it’s the unvaccinated in the less restrictive jurisdictions who are spreading it by not wearing their masks at the establishments that require (but don’t strictly enforce) masks only for the unvaccinated, Israel’s strict vaccine passport system failed to prevent a huge spike in infections and deaths in August-September 2021 after the honeymoon period of May-June. At the very least it’s safe to say that the vaccine, at least after a certain point, does not prevent transmission enough to compensate for the effects of moral hazard, or enough so that post-vaccine transmission under normal conditions is less than pre-vaccine transmission under lockdown conditions. But this gets blamed on the Delta variant instead. Which reportedly evolved in India before the vaccines even came out, so they can use this filthy unwashed third-world country (yes there is an undertone of racism; they view third world countries as festering Petri dishes which they subliminally want to eradicate) as an example of why we all need to be vaccinated to prevent these strains from developing. Hmm, maybe if Israel’s vaccinated spent the honeymoon period under lockdown they would have snuffed it out, but if they were just going to do that then they wouldn’t be incentivized to get vaccinated in the first place!
I spent late nights studying immunology and molecular biology for many months to try and figure out if my theory was even plausible. I read on Wikipedia about how immunotolerance works, and I wondered, if the medullary thymic epithelial cells got transfected by the pseudourylated COVID vaccine, would they destroy or tolerize every T-cell that exhibits immunoreactivity to the spike protein? Or is it more complicated than that? I am still fuzzy on how the major histocompatibility complex works…
And then I came across something that appears to confirm exactly what I feared:
mRNA vaccines take on immune tolerance (nature.com)
This is a study where autoimmunity similar to multiple sclerosis is induced in mice, which are then injected with a pseudourylated mRNA vaccine coding for the protein which they have been made autoimmune to. This has been successful in preventing the progression of the autoimmune disease, meaning that it ERASES immunity to the coded antigen (and it also prevents such immunity from developing if injected prior to inducing mouse model MS).
Let me repeat, ERASES immunity.
Let that sink in.
The author of the article acknowledges that the same technology is used in the mRNA COVID vaccines, but assumes that the difference in effects is due to the use of a different, more immunostimulatory type of lipid nanoparticle, and a foreign antigen instead of an antigen from one’s own body. I find this assumption to be unsatisfactory. First of all, as I have already explained the PEGylated lipid nanoparticle is not necessarily immunostimulatory, and it’s not clear that that was the purpose for such a choice of nanoparticle delivery vehicle anyway. Secondly, the distinction between a foreign antigen and a self-antigen that one has become autoimmune to, at least as far as I am aware, is a false one. The body does not know that the protein that it is autoimmune to is not a foreign antigen or it would not be attacking it in the first place. Maybe there’s more to it that I don’t understand but none of that is satisfactorily elaborated here nor in the sources cited. I’m not going to assume that they know what they’re doing even if it’s beyond my own comprehension until they provide a sound and cogent theory about what is going on.
Note that some of what was observed in this study does not match what we are seeing with the COVID vaccines. For example, the immunotolerance induced in these mice appears to be specific only to the coded antigen, while the mRNA COVID vaccine appears to have a more broadly immunosuppressing effect; according to a preprint (not peer-reviewed, but neither is the study on preventing transmission) a number of markers of innate immune system function are downregulated (which, if true, means that the vaccinated could be more likely to pick up and incubate a COVID infection since the innate immune system is less likely to fend off the viruses before the adaptive immune system needs to be brought in). Although possible long-term generalized immune suppression was considered as a possibility for the mouse study. The immune effects could possibly be caused by the spike protein itself, but it’s hard to tease out which effects are due to the pseudourylated mRNA platform and which are due to the functions of the coded protein, since Novavax isn’t in wide use yet and the use of the adenovirus vectors has been massively curtailed so there isn’t much data comparing the different vaccine platforms with the protein in common. The spike proteins could also be what causes the reduction in T cell function in the COVID vaccinated as the mouse model MS vaccine appears to upregulate T cell function. And while the COVID vaccine produces antibodies to the targeted antigen, at least at first, the mouse model MS vaccine does not - it only produces an initial exhausted T cell response. But it should be noted that the COVID vaccine doesn’t produce antibodies in a lot of people either. It appears that certain diseases are correlated with COVID vaccine failure. This is anecdotal, but I have a step-grandmother with multiple sclerosis who does not produce an antibody response to the COVID vaccine at all. It could be that this type of vaccine has a different effect sometimes in those with autoimmune disorders. Or maybe the human immune system is just different in that way from the mouse’s. The human being has a much bigger body after all, and this could be the result of size causing the immune system to operate more slowly, or the fluid dynamics operating differently.
Could it be that the difference between humans and mice is that in humans antibodies are produced before the immune system is signalled to promote tolerance, and it could take many months for all the spike-reactive lymphocytes to be rooted out and tolerized at which point antibody production has declined to zero? Maybe antibodies are produced at first because most people have been exposed to some or all of the four human-infecting species of common cold coronaviruses which confers partial immunity to the COVID-19 spike protein? Maybe the reason why COVID vaccinated people don’t develop immunity to the other proteins of the coronavirus when they get infected after being vaccinated is because they are tolerized to the spike protein and it causes bystander suppression of any immune response to these proteins? Keep in mind these are all speculations; my imagination is running wild here. Great fodder for science fiction!
However, a delayed immunotolerance model does seem to fit with a lot of the peculiar observations regarding this vaccine. Antibody levels fall after a few months which raises the risk of infection, but the risk of hospitalization and death remains low. Since hospitalization and death is generally caused by the immune response to the virus this is consistent with a long-term suppressed immune response to the virus. Also the vaccine appears to reduce the symptoms of long COVID in some patients. If long COVID is an autoimmune disorder caused by the immune system attacking its own proteins over perceived similarity to epitopes of the spike protein, then it makes sense that this type of vaccine would alleviate this in some patients in a similar way to how it stops the progression of multiple sclerosis in mice.
Oh and I just discovered a story about a man with Wiskott-Aldrich syndrome, a genetic disorder that debilitates the immune system among other things, who was sick with COVID for five months - because of his weakened immune system it wasn’t life-threatening symptoms, just long COVID like symptoms such as fatigue and changes in taste and smell - who was then given the COVID vaccine, two shots a month apart, and he tested negative 72 days after the first shot. You could write this off as coincidence if not for the boost of antibodies it provided him, which is strange since he generally doesn’t have a strong immune response to regular vaccines. There is something peculiar going on here that we do not understand. Or maybe the people that came up with it DO understand, and are deliberately keeping it secret for whatever reason. Though potentially disastrous for the general population, this vaccine might be a miracle drug for certain diseases, but we first have to figure out how it works and study it properly.
Finally a new paper just came out and it’s the study comparing the immunity of the mRNA vaccines to other types of vaccines that I’ve been waiting for:
Humoral and cellular immune memory to four COVID-19 vaccines | bioRxiv
It compares Pfizer and Moderna to J&J and Novavax over a period of six months. It shows that antibody levels decline substantially over this period for the mRNA vaccines (though B cells and T cells remain stable) but not for the other two vaccines. This proves that the antibody decline is caused by the peculiarities of the pseudourylated mRNA platform - or by the presence in the spike protein of the polybasic cleavage site, which is removed in both the Novavax and J&J spike proteins but present in both mRNA vaccine spike proteins. This modification appears to contribute to the improved efficacy of these two and is the reason why the J&J jab was marketed as a one-and-done jab. All four of these vaccines have the double proline modification, which is supposed to make the protein more stable and therefore easier to form antibodies of the right shape but in the study I read here it doesn’t appear to be all that effective.
It would be interesting to compare with Covaxin (an inactivated virus shot made by an Indian biotech, and the only one that MIGHT be made available in the first world) and the Astra-Zeneca jab (uses a different adenovirus vector, from chimpanzees; J&J’s jab uses Ad26 which is the same as one of the two species used in Russia’s Sputnik V). Both of these use the wild-type spike protein. Even more so if Corbevax (an American knockoff of one of the two Cuban vaccines, which I believe are the safest since they use only the RBD epitope of the spike protein - unless this particular piece of the spike turns out to be the part with the alleged prionogenic effects) could also be studied but sadly that one isn’t getting any Bill Gates or government funding, mostly just donations from small businesses. It’s too bad that Dolly Parton is an airhead when it comes to molecular biology; if I were her I would have thrown my millions at Corbevax instead of that shady charity that decided her contribution should go to Moderna.
At least it appears that the adenovirus vector doesn’t cause long-term immune suppression, at least not in a generalized fashion. There was some concern in 2020 about human adenovirus Ad5 (the other vector used in Sputnik V) raising the risk of HIV infection through an unknown mechanism that is not proven to not still be present once the virus is made into a vector. For this reason, if you absolutely HAVE to get a vaccine to avoid ending up on the streets or whatever, and Novavax is not yet available where you live, the J&J vaccine, though the least effective, may also be the safer than the mRNA in the long-term, provided it doesn’t cause microclots or stealth plaques in the blood vessels (it’s actually the most dangerous in the short-term, probably because it doesn’t mute the innate immune response the way pseudourylated RNA does. It’s a DNA virus after all). You may not need a booster since the immunity doesn’t wear off, at least not in the time frame of six months, and if you do get a booster it will be less likely to cause as much damage because you’ll have some immunity to the viral vector so that your immune system might kill most of the vector particles before they can infect your endothelium and cause blood clots.
Not that I’m recommending getting any of these at all. Even Novavax seems to cause some problems due to the inherently toxic nature of the spike protein. My strategy for dealing with the pandemic was always to mostly stay home for a while and wait out the storm. But if my theory is true, then the pseudourylated mRNA platform presents a special kind of danger that I don’t believe the field of medicine or biotechnology has ever posed before, which may result in a storm that is never-ending. Is the new paradigm regarding vaccination not to eradicate the virus, but to commodify it? Not to fight it, but to tolerate it? Replace herd immunity with herd virulence that will make it unsafe to leave the house unless you are vaccinated as well? Genetic discrimination against those that don’t respond well to the vaccine? Who needs mandates when you can change the game theoretical dilemma and make it actually dangerous to be an antivaxxer, loathed as free riders under the herd immunity paradigm, without endangering the righteous - having your cake and eating it too? Supposing it doesn’t kill every one of them in a couple of years, what kind of human being will evolve out of such a system? Even if the pandemic fades from public memory with the distraction of recent events, the damage done will not be reversed. New medical disorders in younger patients will be normalized; diseases such as polio and measles will make a comeback, due both to the public’s understandable newfound hesitancy to even give those shots to their children and the introduction of these crappier new vaccines to replace the old ones; society may well collapse, leaving behind only the types of people that exhibit such dysfunctional traits as the nerve to question authority and think for themselves in subjects they’re not credentialed in. But I am getting far too ahead of myself. Maybe the worst won’t happen. Maybe only some people will turn into Typhoid Marys. All that is clear is that the mRNA vaccines fade quicker than the other vaccines, which in my book makes them inferior, but we still don’t know yet why.
Questions to hopefully be answered in future trials:
-Does a non-mRNA vaccine wear off after six months if given as a booster to someone who was vaccinated with Pfizer or Moderna?
-Are the T-cells and B-cells that continue to be present in mRNA vaccinated people after the antibodies are gone exhausted or otherwise abnormal?
-Is the immune tolerance effect in the mice caused how I think it’s caused - by the vaccine infiltrating AIRE-expressing cells and making them produce protein that they don’t know is foreign thanks to the pseudourylation of the RNA so that they don’t present it on their surface correctly?
-What is the mechanism behind the reduction in innate immunity caused by the mRNA vaccines, if that is indeed what is happening?
-What are the mechanisms behind activation of LINE1 elements to produce reverse transcriptase to transcribe vaccine RNA into DNA, and does it happen in vivo? For that matter, what mechanisms cause the DNA to replicate with the cell, as herpesvirus DNA does, and would that happen with reverse transcribed coronavirus DNA?
-RNA communication through exosomes happens from cell-to-cell in the body all the time but we are only beginning to understand this. Some of this RNA is substituted; these substitutions communicate a subtext that we are unaware of, and the mRNA vaccines may be communicating something else to certain cells besides the protein code. Is this how cancer spreads while evading the immune system? Does it do it by sending vesicles full of RNA for its abnormal proteins into cells involved in immunotolerance so that they think that these proteins are normal?
If we could somehow get the summary of this article in a meme or two, add a few cats, then we might get somewhere with the general population. Your level of specific knowledge is light years beyond mine. My issues with all of this injection nonsense is non-technical, firstly The issue is CHOICE vs FORCE, secondly presuming CHOICE is a human right, then the issue is INFORMED CONSENT & BIOLOGICAL INTEGRITY, then my third issue is that BIOETHICS do not exist in the CovidEra, my fourth is A lack of trust in the dark triad of BigGov, BigBiz (tech/pharma), and BigMedia, as clearly their interests and reality do not align (on this issue, and most others). And my final issue was almost immediately natural immunity, facts, debate, and real science was outlawed because it was counter narrative, or inconvenient to the interests of a select few. Heck this list could continue, but why, the last few years speak for themselves to anyone with the eyes to see, the ears to hear.
Keep doing the good work. I will check out your other articles in the near future.
I haven’t finished reading but wanted to thank you for posting. I’ve read much of this before but you are making the subject much easier to understand for a non-biologist. Thanks.