Here is a pro tip: the antibodies created by the immune system in response to the cmRNA vaccination are isomeric binding abs. They have nothing to do with Sars-Cov-2. We are dealing with TWO types of IgG abs: normal (Sars-Cov-2 coded with Uracil) and isomeric (cmRNA vaccines coded with Pseudouridine). Severe cases of Sars-Cov-2 were caused by two lethal antibodies, REGN10987 and B38. But now, because of the vaccination campaign, we have to deal with isomeric abs (including the isomeric version of the lethal abs which have been described above), which are awaiting an activation. Isomeric abs were discovered in 1994. Pseudouridine (Pseudouracil) is an ISOMER.
"Given the fact that pseudouridylation endows the modified uridine with chemical properties that are distinct from those of all other known nucleotides, introducing Ψ(s) into an RNA will likely alter its function.
Therefore, Ψ has chemical properties that are distinct from that of uridine."
How can these two authors, A. Rossler and J. Quandt (not to mention the peer reviewers) not have any basic knowledge of these undeniable facts of stereochemistry? Their papers should have never been accepted, since they do not understand that the antibodies resulting from the cmRNA vaccines, are ISOMERIC.
It seems that A. Rossler and J. Quandt have no knowledge of basic stereochemistry. How can they babble about "antibodies created by the vaccine", when Uracil has been replaced 100% with Pseudouridine in the cmRNA product? Have they no knowledge even of this fact?
Since a nucleobase (Uracil) has been replaced 100% with a nucleoside (Pseudouracil), the resulting spike proteins will be isomeric (they will have a different chirality/configuration, than spike proteins coded with Uracil). And so will the antibodies.
Then, what is going on, for these authors, and for the peer reviewers of such papers, to IGNORE these basic facts of stereochemistry? Once you replace a nucleobase with an isomer, you change the rules of the game: different biological and chemical functions, a modified chirality.
They seem to think that the resulting antibodies are "normal" antibodies, which they most certainly are not. They seem to ignore that such isomeric abs have nothing to do with Sars-Cov-2.
The question on everybody's mind I am sure is why... why are 'they' doing this?
We can rule out $$$ - if it was about money they'd surely use a more benign formula for their injections... maiming and killing epic numbers of customers is not a good business model
My area of expertise is energy ... and because we pick the low hanging fruit first... what remains is very expensive to extract --- lots of oil etc remains --- but the cost makes most of it non-viable. Unless people think $10 per gallon oil is doable (see hyper inflation).
I've been expecting 'them' to do something ever since I read Perfect Storm a couple of years after the GFC and had an epiphany (OMG - we are f789ed!) and quickly delegated my responsibilities to my underlings (to the chagrin of my business partners!) and set off on an urgent bucket list...
Never in my wildest nightmares did I think that when we approached the Seneca Cliff would 'they' unleash a 'vaccine' intended to exterminate us... I was already getting some feedback that 'he's lost his mind -- he's only mid 40's and he's walking on us cuz of peak oil' (actually the correct term is peak cheap oil)... so imagine if I'd have suggested that we are going to be exterminated... so you should start bucket listing too....
Anyhow... there's over a decade of facts logic and reasoning summarized here... and the more I think about this ... the more what they are doing makes sense https://www.headsupster.com/forumthread?shortId=220
Well, at the moment the prospects that these injections are a successful depop seem narrow, or at least impossible to score accurately. Long term infertility? The signal in the short term isn't apocalyptic. Cancer maybe, or maybe this "trapped on the tolerance raft" one. Maybe the reason it will turn out not to be depop is because no one "at the top" is immune to wishful thinking about teching our way past the EROI crash.
But if you combine the sperm motility issues (Israeli study GatoMalo wrote about) with the menstrual issues with women- it is bound to cause at least short term fertility complications in some couples. Long term remains to be seen. I see this a bit like Eugyppius, that there is a lot of bureaucracy and sadly, not a lot of highly intelligent people, calling most of these shots. No one was thinking of "consequences" in any of the myriad of bad decisions they made to get us here. Could also be that there are darker agendas lurking in the background, the people up front right now are honestly leaving me gobsmacked. The fact that our government rewarded a worm like Fauci with his position is a good example. Also, the FDA and NIH are practically wholly dependent on private Pharmaceutical monies now, so they should no longer be considered quasi-governmental agencies- they are private and therefore incapable of making objective decisions about our public health. Sweden did a great job in completely separating their Health Ministry from the rest of the government. It's how they were able to stand strongly against the politicians pressuring them to lockdown.
As an aside, I just spent time in the comments section (1400 comments in 20 hrs) of the most recent Steve Kirsch substack post refuting virus deniers. If you want to preserve your sanity.. DONT GO THERE. It's saddening that such a large and vocal contingent has been so misled - we could really use them yelling and screaming about the IgG4/tolerance findings instead of defending their cargo cult to the (metaphorical) death.
What? Wow, that's scary. You would think that the whole "lab leak" thing would appeal to many of them (it does seem like out of a Clancy novel, so it would seem easy to get people onboard).
It's very interesting how data can literally be played both ways (for/against OAS). My comment is for figure 4 of the Quandt study. Again I feel like this is just demonstrating the difference between a primary and secondary immune response. If this is a primary immune response to Omicron then there wouldn't be a very strong antibody response to Omicron specific regions of the RBD; however, conserved regions between Wuhan & Omicron would be considered a secondary exposure and therefore much stronger and long-lasting. It would be more interesting to see if any of these individuals were infected again with Omicron - would this secondary exposure to Omicron see an increase in the Omicron specific antibodies? Also, I would expect to see more Wuhan specific B cell proliferation in the face of Omicron infection to prove OAS. Figure S5 shows the RBD between variants and they are still wildly similar even though we are constantly bombarded with how "different" Omicron is. I see that they are not measuring antibodies in this case, but memory B cell (and my confusion may be due to not understanding exactly what the researchers did).
My final thought concerns the WHO severity grade of all participants (grades 1 - 2 or asymptomatic to symptomatic, but recovered without assistance). So the good news is everyone survived regardless of the antibodies/B cells they made. So, in my best Jan Brady voice, "Antibodies, antibodies, antibodies ... all anyone ever talks about is antibodies." Fortunately our immune system has a lot more up its sleeve! Thanks again for making my brain smoke.
Right, especially for the 2-dosed who have had more time for the last spike party to wane, there is a clear targeting of BA.1-binding B Cells / antibodies for expansion, leading to low Wuhan-neutralization for three individuals post-BA.1. "OAS" is so ambiguous though, you can move the goalpost wherever you want. The backboost in antibodies was *not* bigger than the new response; but the B Cells betray that this response isn't "new."
And overall to take the results in reverse, Omi/Wuhan cross-binding B Cells expanded, but these correspond to effective neutralization of BA.1 - therefor, there were already preexisting BA.1-neutralizing antibodies in the pool. (Or, the tests are lying in some way.) And maybe you could run it in reverse with the UT set - spray some Wuhan into their noses and see if their BA.1-based pool cross-neutralizes after reshuffle. In which case "not that different after all" really is the only story here.
RE what they did, there was flow cytometry with tagged spike and tagged RBDs for Wuhan or BA.1. And then there was flow cytometry for targeted conserved / nonconserved epitopes. I didn't use any results from the second one because I haven't seen enough on how they validate the design logic.
"It’s not “original” if you have to shove the thing down the immune system’s craw for so long that tolerance develops before the “imprint” takes hold. I think that’s a fair line in the sand for me to draw."
It's been incredible to watch the science debated and most of it is way over my head so it's deeply appreciated when the conclusion includes a summary we folks in the peanut gallery can understand and remember. Big time thanks for the brainy research & relatable explanations!!
Boy, it's a tall order to suggest that subscribers' progeny have high marriage prospects. I mean, I don't have much expectations for my own progeny, probably because they're non-existent.
This is a lot to go through and I still have yet to fully examine the prior posts, including the IgG4 paper which I forgot to comment on and now forgot much of what I wanted to comment unfortunately 🤦♂️. I am trying to remember if the study appeared to indicate IgG4 antibody formation specifically with the mRNA vaccines. This actually led me to some suspicions, but I want to examine some more information before I make a proper comment.
Regardless, you've been really pumping out a lot of these posts and I commend your work! I should encourage people to donate to your ko-fi, but I'm not sure if that will help with progeny marital status, or maybe it'll eventually cure cancer I'm not sure. You decide!
Er... I'm pretty sure the flyer said 5X Improvement in Progeny Marriage Status MONEY BACK GUARANTEED. So, you know, get to work...
Yes, specificity to mRNA was demonstrated by comparison with vector-injected IgG4 levels, who are the obligate stand-in for an "unvaccinated" control group in the paper!
Wait who's mine? Theirs through subscribing to me or theirs through you? Don't worry this isn't me trying to commit tax evasion...
I'm trying to remember something from the Discussion that the researchers made mention of lack of IgG4 formation for those given a 2nd dose but infected a few weeks afterwards vs those infected a few months after vaccination showing IgG4 production, and from their comments I was confused as to whether their argument was that the IgG4 formation was time-dependent due to the mRNA vaccinations and that IgG4 antibodies should appear in those given 2 doses regardless of infection. I may try to go back to the paper but it's in one of my 100 tabs right now...
And as to the this being mRNA specific, I'm leaning towards the LNPs as adjuvants playing a role in directing this formation. A few papers I have looked up suggest this class switching may be dictated by specific interleukins such as IL-4, IL-10, IL-21, and IL-22 I believe. The 21 and 22 are correct but I can't remember about the others, and so I was quite curious if the LNPs may be causing a cytokine response that may be enhancing production of these IL's that is causing the class shift. I haven't found anything of the sort in regards to which IL's are produced by the LNPs aside from IL-6, so I'm going to have to dig a bit deeper but I guess for the sake of sharing thoughts I should spill the tea on my thoughts at the moment.
There are different ways to look at the infection plots.
First it's sorted by days from dose. So in this cross section you get a picture that the baseline is slowly increasing after the 2nd dose, jumps up after 3rd and then either settles or maybe wanes. However since there's short term expansion and long term conversion, the question is does the baseline start going up again at later time points. So regarding the question you mention, looking at how the baseline changes after days-post-dose answers that.
Second is what happens after the baseline, there's a spike for most, that's probably just expansion. So without long term results for any individual it's impossible to know whether infection accelerates conversion.
My running hunch is that the specificity is actually a quantitative issue: the mRNA just causes more exposure to spike, and maybe more long-term germinal center response per exposure, thanks to the pseudouridine. So you get more tolerance. This coalesces with the Röltgen et al Figure 4 results where BNT162b2 still has way higher antibodies at 3 months (in the A portion of the figure which isn't on this post).
So I suppose the difference between DNA and mRNA vaccines would be that the mRNA production in the adenoviral vector vaccines are fixed and likely to undergo eventual degradation (possibly after phagocytosis or other mechanisms of cell lysis) while the mRNA may provide longer life through pseudouridine. I suppose my question would be how stable the mRNA would be in serum. There is the matter of the germinal centers at least hoarding some of the mRNA so would that indicate some selective recognition? And that may be driven by specific bases being recognized in the mRNA... Sorry, I'm just rambling to figure this out which probably should be the same thing that the pharmaceutical manufacturers are doing.
Between Modern's vote for LNP's, and Brian's vote above for pseudouridine.. for what it's worth I was already on the side of pseudouridine (and the long lived mRNA it allows for) as being the prime, unnatural driver of the IgG4 "tolerance" phenomenon. Great discussion... we are experiencing science moving ahead in real time here.
In reality it really could be be both, with a main problem being that a lot of this should have been figured out beforehand. However, thinking about it now I don't think there was ever an assumption that multiple boosters would be needed if we assume that the initial conceptualization of these vaccines were done with the argument that the vaccines are sterilizing. Hence, two doses and you're done- no problem. But since that didn't happen and many scientists only focus on antibody titers, then that just leads to real-time correction through constant vaccination to make up for something the initial iteration of the vaccine was supposed to have done-sterilization which now takes a backseat to antibodies. So the consequences of multiple vaccinations are due to the original failures and really just sticking a bandage onto a festering wound.
First, thank you for the recommendation to Modern Discontent. Definitely am going to sign up. Second, I like you delineating the difference between OAS and imprinting/tolerance. This idea of waiting long enough after a shot that your body can produce new B cell lines is interesting. I wrote elsewhere about my 40 year old male neighbor who got a booster in November but caught Omicron 6 weeks ago and got severe myocarditis. So in this anecdotal case, 8 months time was insufficient time for those new B lines. I’m also hoping there is not suddenly a new lab leak somewhere to create a new non-Wuhan variety of corona virus to correct this issue, or worse yet, some pharma head thinks they can re-jig an even better vaccine to correct the old one.
On a side note, I’m rewatching The Big Short (my best friend told me to as it is timely in nature right now with our economy) and I’m thinking you are the Mark Baum in this Covid vaccine story 😊. Don’t worry, that’s a compliment.
Thank you Charlotte! I greatly appreciate the support, and it certainly means a lot!
To your comment, I guess there's an issue of messaging with OAS that may not emphasize that OAS can only occur after the infection. It's after the infection that OAS proponents would look at the antibody levels and argue what they see (or don't see). So in the case of your neighbor he is just being vaccinated with the same spike then getting infected many months down the line. OAS would not explain whether he had those new memory B cells targeting new epitopes after vaccination, it would argue whether after the infection he would have them in case of a second infection.
I hope that makes sense. Essentially OAS is being used to predict what may happen to the immune system after an infection based on one's prior history and how that would affect every subsequent infection, but it doesn't explain the situation that happened with your neighbor. This is also a fault of OAS as it is thrown out because this nature of OAS as a hypothesis requires you do a post-hoc analysis and pick results that would substantiate OAS.
Thank you for the presumably flattering casting choice (I still haven't seen it)!
Sorry to hear about your neighbor - Igor's theory is that tolerance will facilitate cardiac complications because, essentially, the virus is being allowed to replicate more - https://igorchudov.substack.com/p/boosters-now-promote-covid-deaths. I agree that the virus is replicating more but I am not sure if we can expect systemic spread or confined to respiratory tract. But your anecdote matches his theory.
Alternately the IgG4 thing wasn't relevant here. It was just a case of the virus being allowed to spread rapidly because antibodies were low after 8 months. It's really hard to tell whether there's still severe efficacy after 6 months because the rollout of additional doses creates statistical illusions (https://unglossed.substack.com/p/the-panera-kingdom-problem). But we can either suppose that there is, and the neighbor was just unlucky (some % of severe outcomes will still occur), or that there isn't (in which case some higher % of severe outcomes will still occur), or that it's negative - in which case Igor's theory above.
I think I lean toward the latter since I am 40, unvaccinated, no big problem with Omicron in January (just 2 days of brain fog).
The generation of new B Cell lines in my "leave the door open" model implies a chance for the virus to make a mess first - just as with any natural infection. The new B Cell lines can't be made instantly, it has to be during and after the infection. But the way I see it is that this is a reality of nature - no pain, no gain. With the injections, you meet the virus when the antibodies are high, it can't spread around the body, great, that's severe efficacy. But if it comes at a price of keeping the antibodies high all the time and developing IgG4, then that's a net loss.
Thank you for your thoughtful answer. There are so many variables to look at with my neighbor's case. But it was very frustrating to hear that the doctor who attended the case did not seem to ascribe any fault belonging to the covid vaccine. I reached out to Igor because of the odd sequence of events, as the booster was given so long ago. Because my neighbor and his wife (both highly intelligent people but not keen on hearing much about the vaccines) are obviously not enthused to hear anymore negative news at this point, I did not mention this recent study I read about demonstrating that unvaccinated are unlikely to get myocarditis when they catch covid, and it seems to be exclusively linked to the vaccines. https://euroweeklynews.com/2022/07/08/no-increase-myocarditis-covid-infection-unvaccinated/
And the character Mark Baum comes across as quite boisterous - but he's the king of truth and no BS in the movie. He's awesome with his straight talk. I'm really enjoying all of the comments between you Modern Discontent/Igor Chudov/Jim H - I actually love that you all diverge at some points- it's much more interesting to think of all of the possibilities.
I think the spread of the virus is likely to be dependent on the spread of the vaccine. Because the mucosal immune system is somewhat compartmentalized relative to the rest of the lymphatic system I think we may argue that the immunity at the point of viral entry would not be severely impeded if that were the case, but that hasn't been looked into extensively which is another shame.
I'm still unvaccinated and I don't think I've caught covid yet either. But I did have recently a very rare mucosal melanoma, so I've been reading a lot about boosting immunity in that area and reducing overall inflammation. One of the people commenting got me reading about ROS and now I'm taking Glutathione to see if it helps. I'm wondering if there isn't some way to specifically help balance the IgG1- IgG4 to get them working optimally to also clear the spike proteins.
Here is a pro tip: the antibodies created by the immune system in response to the cmRNA vaccination are isomeric binding abs. They have nothing to do with Sars-Cov-2. We are dealing with TWO types of IgG abs: normal (Sars-Cov-2 coded with Uracil) and isomeric (cmRNA vaccines coded with Pseudouridine). Severe cases of Sars-Cov-2 were caused by two lethal antibodies, REGN10987 and B38. But now, because of the vaccination campaign, we have to deal with isomeric abs (including the isomeric version of the lethal abs which have been described above), which are awaiting an activation. Isomeric abs were discovered in 1994. Pseudouridine (Pseudouracil) is an ISOMER.
https://pubmed.ncbi.nlm.nih.gov/9217014/
Conformational isomerism of IgG antibodies
https://www.researchgate.net/figure/The-schematic-layout-of-the-IgG-subclasses-and-isomers-thereof-A-The-IgG-subclasses_fig2_267814149
Once Pseudouridine is introduced into the genetic code, the amino acid chains will have a different chirality/configuration:
https://i.postimg.cc/Bnd75wbn/m-gki249f2.jpg
https://i.postimg.cc/0QmsdwPL/tileshop.jpg
"Given the fact that pseudouridylation endows the modified uridine with chemical properties that are distinct from those of all other known nucleotides, introducing Ψ(s) into an RNA will likely alter its function.
Therefore, Ψ has chemical properties that are distinct from that of uridine."
How can these two authors, A. Rossler and J. Quandt (not to mention the peer reviewers) not have any basic knowledge of these undeniable facts of stereochemistry? Their papers should have never been accepted, since they do not understand that the antibodies resulting from the cmRNA vaccines, are ISOMERIC.
It seems that A. Rossler and J. Quandt have no knowledge of basic stereochemistry. How can they babble about "antibodies created by the vaccine", when Uracil has been replaced 100% with Pseudouridine in the cmRNA product? Have they no knowledge even of this fact?
https://web.archive.org/web/20210111092707/https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/
Since a nucleobase (Uracil) has been replaced 100% with a nucleoside (Pseudouracil), the resulting spike proteins will be isomeric (they will have a different chirality/configuration, than spike proteins coded with Uracil). And so will the antibodies.
Then, what is going on, for these authors, and for the peer reviewers of such papers, to IGNORE these basic facts of stereochemistry? Once you replace a nucleobase with an isomer, you change the rules of the game: different biological and chemical functions, a modified chirality.
They seem to think that the resulting antibodies are "normal" antibodies, which they most certainly are not. They seem to ignore that such isomeric abs have nothing to do with Sars-Cov-2.
I love the pro tip! "...is believed to improve the marriage prospects of your progeny" 😄 ❤️
Thanks for this.
The question on everybody's mind I am sure is why... why are 'they' doing this?
We can rule out $$$ - if it was about money they'd surely use a more benign formula for their injections... maiming and killing epic numbers of customers is not a good business model
My area of expertise is energy ... and because we pick the low hanging fruit first... what remains is very expensive to extract --- lots of oil etc remains --- but the cost makes most of it non-viable. Unless people think $10 per gallon oil is doable (see hyper inflation).
I've been expecting 'them' to do something ever since I read Perfect Storm a couple of years after the GFC and had an epiphany (OMG - we are f789ed!) and quickly delegated my responsibilities to my underlings (to the chagrin of my business partners!) and set off on an urgent bucket list...
Never in my wildest nightmares did I think that when we approached the Seneca Cliff would 'they' unleash a 'vaccine' intended to exterminate us... I was already getting some feedback that 'he's lost his mind -- he's only mid 40's and he's walking on us cuz of peak oil' (actually the correct term is peak cheap oil)... so imagine if I'd have suggested that we are going to be exterminated... so you should start bucket listing too....
Anyhow... there's over a decade of facts logic and reasoning summarized here... and the more I think about this ... the more what they are doing makes sense https://www.headsupster.com/forumthread?shortId=220
Well, at the moment the prospects that these injections are a successful depop seem narrow, or at least impossible to score accurately. Long term infertility? The signal in the short term isn't apocalyptic. Cancer maybe, or maybe this "trapped on the tolerance raft" one. Maybe the reason it will turn out not to be depop is because no one "at the top" is immune to wishful thinking about teching our way past the EROI crash.
The problem with any significant depop --- is the supply chains collapse.
And those who survive starve.
Trade-Off
Financial System Supply-Chain Cross-Contagion: a study in global systemic collapse.
David Korowicz
chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/http://feasta.org/wp-content/uploads/2012/10/Trade_Off_Korowicz.pdf
But if you combine the sperm motility issues (Israeli study GatoMalo wrote about) with the menstrual issues with women- it is bound to cause at least short term fertility complications in some couples. Long term remains to be seen. I see this a bit like Eugyppius, that there is a lot of bureaucracy and sadly, not a lot of highly intelligent people, calling most of these shots. No one was thinking of "consequences" in any of the myriad of bad decisions they made to get us here. Could also be that there are darker agendas lurking in the background, the people up front right now are honestly leaving me gobsmacked. The fact that our government rewarded a worm like Fauci with his position is a good example. Also, the FDA and NIH are practically wholly dependent on private Pharmaceutical monies now, so they should no longer be considered quasi-governmental agencies- they are private and therefore incapable of making objective decisions about our public health. Sweden did a great job in completely separating their Health Ministry from the rest of the government. It's how they were able to stand strongly against the politicians pressuring them to lockdown.
As an aside, I just spent time in the comments section (1400 comments in 20 hrs) of the most recent Steve Kirsch substack post refuting virus deniers. If you want to preserve your sanity.. DONT GO THERE. It's saddening that such a large and vocal contingent has been so misled - we could really use them yelling and screaming about the IgG4/tolerance findings instead of defending their cargo cult to the (metaphorical) death.
If you must; https://stevekirsch.substack.com/p/if-viruses-dont-exist-then-how-can
What? Wow, that's scary. You would think that the whole "lab leak" thing would appeal to many of them (it does seem like out of a Clancy novel, so it would seem easy to get people onboard).
You’re a brave man Jim! Here’s another valiant attempt to persuade the anti-germ theorists. I really like his Substack too: https://amidwesterndoctor.substack.com/p/thoughts-on-the-existence-of-viruses?r=ri0y2&utm_medium=ios
It's very interesting how data can literally be played both ways (for/against OAS). My comment is for figure 4 of the Quandt study. Again I feel like this is just demonstrating the difference between a primary and secondary immune response. If this is a primary immune response to Omicron then there wouldn't be a very strong antibody response to Omicron specific regions of the RBD; however, conserved regions between Wuhan & Omicron would be considered a secondary exposure and therefore much stronger and long-lasting. It would be more interesting to see if any of these individuals were infected again with Omicron - would this secondary exposure to Omicron see an increase in the Omicron specific antibodies? Also, I would expect to see more Wuhan specific B cell proliferation in the face of Omicron infection to prove OAS. Figure S5 shows the RBD between variants and they are still wildly similar even though we are constantly bombarded with how "different" Omicron is. I see that they are not measuring antibodies in this case, but memory B cell (and my confusion may be due to not understanding exactly what the researchers did).
My final thought concerns the WHO severity grade of all participants (grades 1 - 2 or asymptomatic to symptomatic, but recovered without assistance). So the good news is everyone survived regardless of the antibodies/B cells they made. So, in my best Jan Brady voice, "Antibodies, antibodies, antibodies ... all anyone ever talks about is antibodies." Fortunately our immune system has a lot more up its sleeve! Thanks again for making my brain smoke.
Right, especially for the 2-dosed who have had more time for the last spike party to wane, there is a clear targeting of BA.1-binding B Cells / antibodies for expansion, leading to low Wuhan-neutralization for three individuals post-BA.1. "OAS" is so ambiguous though, you can move the goalpost wherever you want. The backboost in antibodies was *not* bigger than the new response; but the B Cells betray that this response isn't "new."
And overall to take the results in reverse, Omi/Wuhan cross-binding B Cells expanded, but these correspond to effective neutralization of BA.1 - therefor, there were already preexisting BA.1-neutralizing antibodies in the pool. (Or, the tests are lying in some way.) And maybe you could run it in reverse with the UT set - spray some Wuhan into their noses and see if their BA.1-based pool cross-neutralizes after reshuffle. In which case "not that different after all" really is the only story here.
RE what they did, there was flow cytometry with tagged spike and tagged RBDs for Wuhan or BA.1. And then there was flow cytometry for targeted conserved / nonconserved epitopes. I didn't use any results from the second one because I haven't seen enough on how they validate the design logic.
"It’s not “original” if you have to shove the thing down the immune system’s craw for so long that tolerance develops before the “imprint” takes hold. I think that’s a fair line in the sand for me to draw."
It's been incredible to watch the science debated and most of it is way over my head so it's deeply appreciated when the conclusion includes a summary we folks in the peanut gallery can understand and remember. Big time thanks for the brainy research & relatable explanations!!
Thank you for the encouraging comment!
Boy, it's a tall order to suggest that subscribers' progeny have high marriage prospects. I mean, I don't have much expectations for my own progeny, probably because they're non-existent.
This is a lot to go through and I still have yet to fully examine the prior posts, including the IgG4 paper which I forgot to comment on and now forgot much of what I wanted to comment unfortunately 🤦♂️. I am trying to remember if the study appeared to indicate IgG4 antibody formation specifically with the mRNA vaccines. This actually led me to some suspicions, but I want to examine some more information before I make a proper comment.
Regardless, you've been really pumping out a lot of these posts and I commend your work! I should encourage people to donate to your ko-fi, but I'm not sure if that will help with progeny marital status, or maybe it'll eventually cure cancer I'm not sure. You decide!
Er... I'm pretty sure the flyer said 5X Improvement in Progeny Marriage Status MONEY BACK GUARANTEED. So, you know, get to work...
Yes, specificity to mRNA was demonstrated by comparison with vector-injected IgG4 levels, who are the obligate stand-in for an "unvaccinated" control group in the paper!
Wait who's mine? Theirs through subscribing to me or theirs through you? Don't worry this isn't me trying to commit tax evasion...
I'm trying to remember something from the Discussion that the researchers made mention of lack of IgG4 formation for those given a 2nd dose but infected a few weeks afterwards vs those infected a few months after vaccination showing IgG4 production, and from their comments I was confused as to whether their argument was that the IgG4 formation was time-dependent due to the mRNA vaccinations and that IgG4 antibodies should appear in those given 2 doses regardless of infection. I may try to go back to the paper but it's in one of my 100 tabs right now...
And as to the this being mRNA specific, I'm leaning towards the LNPs as adjuvants playing a role in directing this formation. A few papers I have looked up suggest this class switching may be dictated by specific interleukins such as IL-4, IL-10, IL-21, and IL-22 I believe. The 21 and 22 are correct but I can't remember about the others, and so I was quite curious if the LNPs may be causing a cytokine response that may be enhancing production of these IL's that is causing the class shift. I haven't found anything of the sort in regards to which IL's are produced by the LNPs aside from IL-6, so I'm going to have to dig a bit deeper but I guess for the sake of sharing thoughts I should spill the tea on my thoughts at the moment.
There are different ways to look at the infection plots.
First it's sorted by days from dose. So in this cross section you get a picture that the baseline is slowly increasing after the 2nd dose, jumps up after 3rd and then either settles or maybe wanes. However since there's short term expansion and long term conversion, the question is does the baseline start going up again at later time points. So regarding the question you mention, looking at how the baseline changes after days-post-dose answers that.
Second is what happens after the baseline, there's a spike for most, that's probably just expansion. So without long term results for any individual it's impossible to know whether infection accelerates conversion.
My running hunch is that the specificity is actually a quantitative issue: the mRNA just causes more exposure to spike, and maybe more long-term germinal center response per exposure, thanks to the pseudouridine. So you get more tolerance. This coalesces with the Röltgen et al Figure 4 results where BNT162b2 still has way higher antibodies at 3 months (in the A portion of the figure which isn't on this post).
So I suppose the difference between DNA and mRNA vaccines would be that the mRNA production in the adenoviral vector vaccines are fixed and likely to undergo eventual degradation (possibly after phagocytosis or other mechanisms of cell lysis) while the mRNA may provide longer life through pseudouridine. I suppose my question would be how stable the mRNA would be in serum. There is the matter of the germinal centers at least hoarding some of the mRNA so would that indicate some selective recognition? And that may be driven by specific bases being recognized in the mRNA... Sorry, I'm just rambling to figure this out which probably should be the same thing that the pharmaceutical manufacturers are doing.
Between Modern's vote for LNP's, and Brian's vote above for pseudouridine.. for what it's worth I was already on the side of pseudouridine (and the long lived mRNA it allows for) as being the prime, unnatural driver of the IgG4 "tolerance" phenomenon. Great discussion... we are experiencing science moving ahead in real time here.
In reality it really could be be both, with a main problem being that a lot of this should have been figured out beforehand. However, thinking about it now I don't think there was ever an assumption that multiple boosters would be needed if we assume that the initial conceptualization of these vaccines were done with the argument that the vaccines are sterilizing. Hence, two doses and you're done- no problem. But since that didn't happen and many scientists only focus on antibody titers, then that just leads to real-time correction through constant vaccination to make up for something the initial iteration of the vaccine was supposed to have done-sterilization which now takes a backseat to antibodies. So the consequences of multiple vaccinations are due to the original failures and really just sticking a bandage onto a festering wound.
First, thank you for the recommendation to Modern Discontent. Definitely am going to sign up. Second, I like you delineating the difference between OAS and imprinting/tolerance. This idea of waiting long enough after a shot that your body can produce new B cell lines is interesting. I wrote elsewhere about my 40 year old male neighbor who got a booster in November but caught Omicron 6 weeks ago and got severe myocarditis. So in this anecdotal case, 8 months time was insufficient time for those new B lines. I’m also hoping there is not suddenly a new lab leak somewhere to create a new non-Wuhan variety of corona virus to correct this issue, or worse yet, some pharma head thinks they can re-jig an even better vaccine to correct the old one.
On a side note, I’m rewatching The Big Short (my best friend told me to as it is timely in nature right now with our economy) and I’m thinking you are the Mark Baum in this Covid vaccine story 😊. Don’t worry, that’s a compliment.
Thank you Charlotte! I greatly appreciate the support, and it certainly means a lot!
To your comment, I guess there's an issue of messaging with OAS that may not emphasize that OAS can only occur after the infection. It's after the infection that OAS proponents would look at the antibody levels and argue what they see (or don't see). So in the case of your neighbor he is just being vaccinated with the same spike then getting infected many months down the line. OAS would not explain whether he had those new memory B cells targeting new epitopes after vaccination, it would argue whether after the infection he would have them in case of a second infection.
I hope that makes sense. Essentially OAS is being used to predict what may happen to the immune system after an infection based on one's prior history and how that would affect every subsequent infection, but it doesn't explain the situation that happened with your neighbor. This is also a fault of OAS as it is thrown out because this nature of OAS as a hypothesis requires you do a post-hoc analysis and pick results that would substantiate OAS.
Thank you for the presumably flattering casting choice (I still haven't seen it)!
Sorry to hear about your neighbor - Igor's theory is that tolerance will facilitate cardiac complications because, essentially, the virus is being allowed to replicate more - https://igorchudov.substack.com/p/boosters-now-promote-covid-deaths. I agree that the virus is replicating more but I am not sure if we can expect systemic spread or confined to respiratory tract. But your anecdote matches his theory.
Alternately the IgG4 thing wasn't relevant here. It was just a case of the virus being allowed to spread rapidly because antibodies were low after 8 months. It's really hard to tell whether there's still severe efficacy after 6 months because the rollout of additional doses creates statistical illusions (https://unglossed.substack.com/p/the-panera-kingdom-problem). But we can either suppose that there is, and the neighbor was just unlucky (some % of severe outcomes will still occur), or that there isn't (in which case some higher % of severe outcomes will still occur), or that it's negative - in which case Igor's theory above.
I think I lean toward the latter since I am 40, unvaccinated, no big problem with Omicron in January (just 2 days of brain fog).
The generation of new B Cell lines in my "leave the door open" model implies a chance for the virus to make a mess first - just as with any natural infection. The new B Cell lines can't be made instantly, it has to be during and after the infection. But the way I see it is that this is a reality of nature - no pain, no gain. With the injections, you meet the virus when the antibodies are high, it can't spread around the body, great, that's severe efficacy. But if it comes at a price of keeping the antibodies high all the time and developing IgG4, then that's a net loss.
Thank you for your thoughtful answer. There are so many variables to look at with my neighbor's case. But it was very frustrating to hear that the doctor who attended the case did not seem to ascribe any fault belonging to the covid vaccine. I reached out to Igor because of the odd sequence of events, as the booster was given so long ago. Because my neighbor and his wife (both highly intelligent people but not keen on hearing much about the vaccines) are obviously not enthused to hear anymore negative news at this point, I did not mention this recent study I read about demonstrating that unvaccinated are unlikely to get myocarditis when they catch covid, and it seems to be exclusively linked to the vaccines. https://euroweeklynews.com/2022/07/08/no-increase-myocarditis-covid-infection-unvaccinated/
And the character Mark Baum comes across as quite boisterous - but he's the king of truth and no BS in the movie. He's awesome with his straight talk. I'm really enjoying all of the comments between you Modern Discontent/Igor Chudov/Jim H - I actually love that you all diverge at some points- it's much more interesting to think of all of the possibilities.
I think the spread of the virus is likely to be dependent on the spread of the vaccine. Because the mucosal immune system is somewhat compartmentalized relative to the rest of the lymphatic system I think we may argue that the immunity at the point of viral entry would not be severely impeded if that were the case, but that hasn't been looked into extensively which is another shame.
I'm still unvaccinated and I don't think I've caught covid yet either. But I did have recently a very rare mucosal melanoma, so I've been reading a lot about boosting immunity in that area and reducing overall inflammation. One of the people commenting got me reading about ROS and now I'm taking Glutathione to see if it helps. I'm wondering if there isn't some way to specifically help balance the IgG1- IgG4 to get them working optimally to also clear the spike proteins.