Why are birds such good reservoirs of Influenza strains? Or, rather, some bird species?
Is it because they have had millions of years of exposure and humans have only been keeping such birds for perhaps 10,000 years and even then not all human groups have close association to birds?
Very interesting link, thanks. In general there's probably compromise (ie attenuation) over time after a HA re-crosses over from the avian reservoir. But the 1918 mutants without 286 don't appear to lose any pathogenicity.
"Humans far and wide, despite being “sinned” with immunity to previously circulating groups/strains, had mounted an immune response tailored to a “subsequent” strain."
Here in Ohio, we also try to avoid uttering the vulgar name of that school as much as possible. Instead we refer to it as "that school up North" (TSUN).
Ha - I wanted to keep using "The Virus Laboratory" as appeared in the letterhead of papers for the PR8 vaccine. But that fell out of use, so I had to get creative ("The Department" was too vague).
Be nice guys... it's just possible that another reader of this blog may have been born in that town, while their father was pursuing grad work at that school. : )
Ok, I admit, some of your data is pushing on my barriers of comprehension. I understand how you don't think OAS exists, but what about "tolerance"- as explained by Igor Chudov? Is that something different? Similar?
OAS, if used coherently, leads to a set of predictions along the lines of novel, but related designs of a virus not needing to evolve any further - because no new memory immunity is created to compensate for whatever they changed. However, in practice you will usually see "OAS" used to explain hyper-mutation (ie Omicron), which is incoherent.
Tolerance implies lack of immune response to a certain motif. So it rewards non-change even more. So, intuitively, if everyone has been made tolerant to Wuhan spike, the only hope is that the current model spike (and other viral antigens) are different enough to prompt a novel response. OAS would say this can't happen, and so the vaxxed are doomed; fortunately OAS is not real. Still, they have to be infected with the new variant virus before they can generate new tolerance-free immunity against the non-Wuhan epitopes, so they are all back to square one as far as needing real natural immunity; and, there is still an evolutionary reward for the virus to revert to tolerated Wuhan epitopes afterward to escape said natural immunity afterward.
Honestly, people need to stop looking at the N-antibodies and using that as an argument for OAS. Full stop. OAS offers no explanation as to what happens to other antigens, if OAS as a theory is to be believed. I have no idea why this argument continues to exist, and in some regard I blame such an argument on the person who brought OAS onto Substack himself- Alex Berenson. Not to say that Alex Berenson should be fully blamed, but Alex Berenson is not without criticisms for his inability to sometimes read science. So Alex was one of the first people to look at the UK surveillance and posit about OAS and reference the N protein, yet he was absolutely wrong to do so, and yet the lack of anti-N antibodies argument lives on. I argue this point because Alex appears to sometimes just take news articles' words on ivermectin and go, "aha! See! It totally doesn't work!" Such an argument should cause people to raise questions about his ability to assess OAS and apply that information, but instead Alex was correct on OAS and the anti-N antibody argument but wrong on Ivermectin, when in fact it should be the analysis of the methodology that should substantiated or refute an idea.
I hope this doesn't seem too critical, but there's been so much whataboutisms formed from a heavily unsubstantiated claim that just continues to live on. Rather than ask, examine where the spike antigen is relative to the N protein, understand whether the immune system would be able to target the N protein, and if so when? If not, what may be happening to cause the immune system from being able to target the antigen?
There's some context to this in my post about why the spike was the main antigen to target in the vaccines:
No need to be so strident Modern.. I have great respect for Brian's views on this and I am just catching up. Regardless of the N-antigen factor, there is something that scientists are calling, "Imprinting" that sounds like a concept similar to the thing I shall not name - see below. Are these scientists wrong in what they are contending?
"Professor Rosemary Boyton, from Imperial's Department of Infectious Disease, says: "Our first encounter with spike antigen either through infection or vaccination shapes our subsequent pattern of immunity through immune imprinting. Exposure to different spike proteins can result in reduced or enhanced responses to variants further down the line. This has important implications for future proofing vaccine design and dosing strategies."
As far as I know, our immune systems have never before been pounded by a single, disembodied (from the entirety of the virus and its overall mosaic of proteins) antigen. By not presenting the entire virus, as all classical vaccines do, the mRNA transfections are not providing our immune systems with full information about the actual virus. While mostly recognized as an innate immune system function, our bodies do have active pattern recognition;
Surely getting pounded over and over again with this disembodied single epitope from a non-conserved region is going to negatively affect our immune system's ability to learn the broader repertoire of proteins since those T-cells will get called up immediately upon a real infection in the transfected, while other learning will take time. Maybe this learning of other proteins gets drowned out to some extent because of this temporal delay.
Forget OAS... I do think it's a distraction. There is something new happening that is the result of these first-of-a-kind single epitope transfections that needs a new name. My gut is that the problem lies in a higher, pattern recognition function. Let's not please be so arrogant as to imagine that we fully understand the function of our immune systems - we are still trying to grasp higher level aspects as discussed in this modelling work;
Title: Understanding adaptive immune system as reinforcement learning
"The adaptive immune system of vertebrates can detect, respond to, and memorize diverse pathogens from past experience. While the clonal selection of T helper (Th) cells is the simple and established mechanism to better recognize new pathogens, the question that still remains unexplored is how the Th cells can acquire better ways to bias the responses of immune cells for eliminating pathogens more efficiently by translating the recognized antigen information into regulatory signals. In this work, we address this problem by associating the adaptive immune network organized by the Th cells with reinforcement learning (RL). By employing recent advancements of network-based RL, we show that the Th immune network can acquire the association between antigen patterns of and the effective responses to pathogens. Moreover, the clonal selection as well as other intercellular interactions are derived as a learning rule of the network. We also demonstrate that the stationary clone-size distribution after learning shares characteristic features with those observed experimentally. Our theoretical framework may contribute to revising and renewing our understanding of adaptive immunity as a learning system."
Another extract from the introduction of the same paper makes my point more clearly:
"Despite the availability of the latest experimental technologies, revealing the principles of such complex learning dynamics is still intricate because the immunological dynamics is shaped and organized by the collective interactions of
the entire immune cell population, which prevents us from simply reducing the problem down to the mere existence of specific cell types or molecules. "
Apologies if it appears aggressive, it's mostly that I have no idea why such an argument for the N protein lives on today when it shouldn't have started in the first place.
I will criticize how you frame your comment asking if they [those scientists] are wrong in their contention, mostly because we need to get away from the right/wrong paradigm. How do we define something as being right or wrong? In order to see if something is right, we need to see if the information and evidence that is being presented is accurate and substantiated. But at the point we look at the evidence then we don't need to argue if something is right or wrong, we need to argue if the evidence is there.
So it's not whether the scientists are wrong, but if their claims are substantiated from their work.
Ironically, I have criticized the author's recent work in one of my posts, which appears to be an update to their December post:
This again is an example of a paper that appears to be circulating and being claimed to indicate that vaccines are causing immune imprinting, but there's many flaws with the methodology.
From those flaws I would argue that these researchers don't appear to have their claims substantiated by their results due to issues with their results.
As to a single antigen there are flu vaccines that only contain the HA antigen, but what makes this unique is the use of the body as the machinery to produce the spike which has possible ramifications.
Technically, there are likely to be conserved regions of the spike, but the receptor-binding domain is under constant selective pressure to mutate and that's usually considered the important region for sticking.
The general issue is that the entire immune system is complex- far more complex than the way it is taught and far more complex than how we've discussed it so there's plenty of things going on that either were not accounted for or that we have not known about before.
I absolutely commend your desire to learn more about all this! I will offer up a few suggestions to hone what you have already presented above:
Many vaccines do not use the whole organism whether it be bacterial or viral in nature. For example, Hepatitis B is a viral vaccine based on a surface antigen (however, it is the actual antigen and not mRNA so it would be more like Novavax, please see https://moderndiscontent.substack.com/p/all-roads-lead-to-spike-protein). And vaccines against the Tetanus and Diphtheria bacterium use inactivated toxins. Please also note that many of these vaccines have gone through several iterations before we got the gems we currently have. Just a side note as I am currently reading Dissolving Illusions about the smallpox vaccine and the parallels to our current predicament are rather alarming.
Also your comment "single disembodied epitope" isn't quite right. Think of the spike protein as your hand. When we produce antibodies against an antigen they will only present a small part of the antigen which is called an epitope. So you might form an antibody against the knuckle of your thumb and another against the tip of your ring finger. We all have unique HLA (molecules found on the surface of our cells which present pieces of antigens or epitopes found within the cell to immune systems cells). So we can all theoretically present different (to a certain degree) epitopes which can be used as models for antibodies i.e. my spike antibodies maybe different from your spike antibodies. There are examples of this in the supplemental material (table S4) from the first study you mentioned above. Please also see https://moderndiscontent.substack.com/p/about-the-immune-printing-study as both Brian & Modern Discontent have great discussion on this paper.
And your final point is spot on. I have learned so much this past year and there is nothing simple about the immune system - there's like a bazillion things going on at once. We attempt to simply things... but there is so much nuance needed. Best wishes in your continued learning!!
Appreciation of our lack of understanding of the immune system is one reason I am reluctant to leap to any "this study says X is happening, and it shouldn't" stories, like "spike going to the nucleus" or "innate immune programming." These things are probably overblown. The IgG4 one was a really big exception!
So I agree with your first principles argument 100%. We shouldn't assume that a disembodied spike is an appropriate way to introduce a pattern recognition machine to a virus. How does it "know" that whatever protein the mRNA is coding is not pollen (allergic sensitization or tolerance) without the normal symphony of DAMPS from cells exploding with virus all over the place? It probably doesn't (though the "logic" of the structure of the spike may correct for this in some ways, like an APC still knows to focus on the receptor binding peptides for presentation). And now we see tolerance coming to roost.
RE "imprinting," which is just a rebranding of our regular understanding of immunity (https://unglossed.substack.com/i/65079519/4-is-immune-imprinting-any-different-from-the-current-understanding-of-b-cell-immunity) I disagree that it is important for vaccine strategy for SARS-CoV-2 *in practice* because there will never be a solution. Either we cut our losses and accept that getting sick is a part of life or we keep chasing the impossible dream of front-loading antibodies to future variants as if the immune system is as reprogrammable as a smartphone app. I think a lot of this is niche programmers trying to take over biology as a whole because they know they will be rewarded if their products fail to get results and non-programmers in science won't be able to critique them. "Imprinting" is a way to put immunology in their black box.
It is not in fact the case that "breakthrough" infections result in lower seroconversion against N - https://unglossed.substack.com/p/the-hot-spot#footnote-6 - Impressions to the contrary are an artifact of selection bias (the UK blood donor pool) or exclusive grading of early spring 2021 results (the Modern N antibodies paper). Further, OAS would not predict anything about N antibodies since those are unrelated to the spike protein encoded by the mRNA/DNA transfections.
Hmmm... my gut instinct remains that there is something afoot related to the vax pounding by a single epitope that does in fact impair the formation of broader immunity, of which N-protein antibodies would be a part. If we think about what is happening in the first days of a natural infection of a mRNA vax'ed person, they would have immediate recall of Wuhan-S, but it would take some time for the same person's immune system to learn N. Our immune systems did not evolve to do something useful with just one epitope from a given pathogen.. it's unnatural.
Is the UK blood donor pool related to the somewhat famous UK week 42 surveillance report where they admitted in writing that vax'ed were not displaying N-antibodies?
The same. And I commented at the time, 9 months ago, that it sounded like they simply weren't taking selection bias (infected less likely to donate) into account. Which is why the more rigorous sampling in Whitaker, H. et al. whih finds near-universal N-seroconversion is a better view of outcomes. So just as with this OAS review the main them is that published science spends most of its time in intellectual slacker mode.
The Covid vaccine don't prevent infection. That means they don't prevent the immune system from eventually encountering N protein. That means that the immune system has to somehow "know" that N protein and spike protein are part of the same entity to suppress a response to the former. It doesn't make much sense imo.
This is so true - I could not understand why people were jumping up and down over that graph. It is blood donors (of unknown infection status). From that graph you can see they were starting off with about 10% of the blood donor population being previously infected as S & N antibodies were similar. After the vax is rolled out S antibodies take off to nearly 100% (that was the point of the vaccine) while N antibodies slowly creep to 20%. What can you glean from the graph: even at week 42 people are still making N antibodies in spite of the fact that they were exposed to the vaccine. If we want to claim OAS then sample people infected after vaccination - did they make N antibodies or not. This graph is utterly useless other than to say that approximately 20% of blood donors as of week 42 had been infected & nearly 100% have been vaccinated. That's it. I made a comment on Alex's original post as I found the chart on page 25 much more useful (recovered persons were killing it on their antibody levels compared to the vaccinated over time). Sigh... thank you for your tireless work to try and get people to understand!
Thank you so much for taking the time to explain that! It leads to some interesting ideas, because if versions of Omicron persist, many people might continue to fall ill (who are vaccinated). It’s scary to think that then a lab or health agency 😳might consider releasing a new non-Wuhan wild type in order to help this subset of people recover.
I personally like the idea that Omicron was a purposeful lab leak (a well intentioned rogue lab) 😂 The whole idea of it being discovered with 4 foreigners traveling in Botswana(never identified) well it kind of sounds like intelligence agency stuff...
But what does it mean? I've noticed so much disagreement among those experts in virology. You'd think the immune system would have been figured out by now. The hubris of scientists who would tell us the introduction of strange things like trillions of spike proteins running loose in the body will save us because they know best. Unfortunately, what they know best seems to change over the years.
I would actually disagree. I think modernity has made us assume that we're near the end of science as we know it, but we're probably nowhere near the middle. Much of the scientific fields are still young relative to our history, and most certainly our modern history. I think this all comes down to science having a severe messaging problem where science has sold people the concept that they will be offered the moon when science has so many leaps to overcome before we even get near that point.
We're now seeing that these vaccines are causing people to think that some sort of mRNA vaccine is on the way now. Elon Musk's attempts to get to Mars has somehow made us believe that we're just a few years off before we all start engaging in space travel. I saw a recent segment from the Today Show where they were talking about this new monoclonal therapy for colorectal cancer that had 100% remission in the very small population that was given it. Did they discuss what they monoclonal therapy was, what genetic mutation it targeted, or anything such as that? No, the hosts started talking about how this means we're near defeating cancer when there's absolutely no way of knowing any of that from that tiny study and the grander complexity of cancer.
So I think we should remember that science is nowhere near figuring everything out, and with the immune system we are learning things that originally was part of the scientific consensus.
Heck, it was only a few years ago that researchers have found out that the innate immune system is actually trainable when it has been considered a static entity for decades!
I agree with everything you said. My problem with this whole vaccine issue, outside the fact that I and my family were hassled, especially early on for not taking the jab, for not accepting the words of known liars, was that it was politicized. I was told I was not being patriotic for refusing the vaccine. That was a message put out by the government and its media. As well as pushing fear. These are the words of Dr. Birx talking about what she knew early on, "I knew these vaccines were not going to protect against infection. And I think we overplayed the vaccines." Are those the words of someone who deserves trust? Who along with Fauci and the president said the vaccine will protect against infection and transmission. Fauci lied then. I doubt the president was in the loop, so he felt he was telling the truth. I've been taking certain things to protect me and I never got it despite rarely wearing a mask and being at concerts. Maybe my protocol worked, it's hard to say for sure. My entire family got Omicron and were mildly sick for around five days. They never got around to taking the Quecetin, D3, C, Zinc and NAC I've been on for many months. I would hope they are somewhat protected from having had it via acquired immunity. That was awhile ago, since then many of our vaccinated friends have had Omicron multiple times. Just anecdotal, but I like the fact I don't have trillions of spike proteins we were told would stay localized, but were later found having traveled throughout the body, with unknown consequences for the future. It simply comes down to a matter of trust. Big pharma and the government have not earned any trust whatsoever, especially when vast sums of money and control over the lives of many millions are involved.
OAS implies that the immune system is fundamentally unable to adapt, which makes no sense since memory immunity *is* plastic. OAS not being real means that the immune system can adapt.
Now that I can understand, but at this point of incredible scientific knowledge, why still all the studies, trials, tests to figure out what the heck is really going on? I honestly have lost faith in those studying this area of the complex systems of the human body. Mainly because many incredibly smart people claim that they finally figured it out, and the claims regularly contradict each other. What I'm trying to say is no one who reads this stuff can be sure, in fact it's not possible to be sure who is right, and that's kinda scary.
An interesting other question here is:
Why are birds such good reservoirs of Influenza strains? Or, rather, some bird species?
Is it because they have had millions of years of exposure and humans have only been keeping such birds for perhaps 10,000 years and even then not all human groups have close association to birds?
Others speculate that increased glycosylation is the cause decreased immunity to newer strains:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719814/
They expend a great deal of effort looking at the replication efficiency and virulence tradeoffs of more or less glycosylation on the HA binding site.
However, no one seems to be looking at how nutrition affects the ability of hosts to fight off viruses.
Very interesting link, thanks. In general there's probably compromise (ie attenuation) over time after a HA re-crosses over from the avian reservoir. But the 1918 mutants without 286 don't appear to lose any pathogenicity.
Do I detect sarcasm about Original Antigenic Sin?
"Humans far and wide, despite being “sinned” with immunity to previously circulating groups/strains, had mounted an immune response tailored to a “subsequent” strain."
Absolutely - I consider OAS a big farce, essentially.
The "Ann Arbor school." Ha ha ha
Here in Ohio, we also try to avoid uttering the vulgar name of that school as much as possible. Instead we refer to it as "that school up North" (TSUN).
Ha - I wanted to keep using "The Virus Laboratory" as appeared in the letterhead of papers for the PR8 vaccine. But that fell out of use, so I had to get creative ("The Department" was too vague).
Be nice guys... it's just possible that another reader of this blog may have been born in that town, while their father was pursuing grad work at that school. : )
Ok, I admit, some of your data is pushing on my barriers of comprehension. I understand how you don't think OAS exists, but what about "tolerance"- as explained by Igor Chudov? Is that something different? Similar?
OAS, if used coherently, leads to a set of predictions along the lines of novel, but related designs of a virus not needing to evolve any further - because no new memory immunity is created to compensate for whatever they changed. However, in practice you will usually see "OAS" used to explain hyper-mutation (ie Omicron), which is incoherent.
Tolerance implies lack of immune response to a certain motif. So it rewards non-change even more. So, intuitively, if everyone has been made tolerant to Wuhan spike, the only hope is that the current model spike (and other viral antigens) are different enough to prompt a novel response. OAS would say this can't happen, and so the vaxxed are doomed; fortunately OAS is not real. Still, they have to be infected with the new variant virus before they can generate new tolerance-free immunity against the non-Wuhan epitopes, so they are all back to square one as far as needing real natural immunity; and, there is still an evolutionary reward for the virus to revert to tolerated Wuhan epitopes afterward to escape said natural immunity afterward.
So if not OAS, what is causing the vax'ed to have difficulty forming N-antibodies upon infection compared to the unvax'ed?
Honestly, people need to stop looking at the N-antibodies and using that as an argument for OAS. Full stop. OAS offers no explanation as to what happens to other antigens, if OAS as a theory is to be believed. I have no idea why this argument continues to exist, and in some regard I blame such an argument on the person who brought OAS onto Substack himself- Alex Berenson. Not to say that Alex Berenson should be fully blamed, but Alex Berenson is not without criticisms for his inability to sometimes read science. So Alex was one of the first people to look at the UK surveillance and posit about OAS and reference the N protein, yet he was absolutely wrong to do so, and yet the lack of anti-N antibodies argument lives on. I argue this point because Alex appears to sometimes just take news articles' words on ivermectin and go, "aha! See! It totally doesn't work!" Such an argument should cause people to raise questions about his ability to assess OAS and apply that information, but instead Alex was correct on OAS and the anti-N antibody argument but wrong on Ivermectin, when in fact it should be the analysis of the methodology that should substantiated or refute an idea.
I hope this doesn't seem too critical, but there's been so much whataboutisms formed from a heavily unsubstantiated claim that just continues to live on. Rather than ask, examine where the spike antigen is relative to the N protein, understand whether the immune system would be able to target the N protein, and if so when? If not, what may be happening to cause the immune system from being able to target the antigen?
There's some context to this in my post about why the spike was the main antigen to target in the vaccines:
https://moderndiscontent.substack.com/i/65685220/targeting-another-antigen
No need to be so strident Modern.. I have great respect for Brian's views on this and I am just catching up. Regardless of the N-antigen factor, there is something that scientists are calling, "Imprinting" that sounds like a concept similar to the thing I shall not name - see below. Are these scientists wrong in what they are contending?
https://www.sciencedaily.com/releases/2021/12/211202162157.htm
"Professor Rosemary Boyton, from Imperial's Department of Infectious Disease, says: "Our first encounter with spike antigen either through infection or vaccination shapes our subsequent pattern of immunity through immune imprinting. Exposure to different spike proteins can result in reduced or enhanced responses to variants further down the line. This has important implications for future proofing vaccine design and dosing strategies."
As far as I know, our immune systems have never before been pounded by a single, disembodied (from the entirety of the virus and its overall mosaic of proteins) antigen. By not presenting the entire virus, as all classical vaccines do, the mRNA transfections are not providing our immune systems with full information about the actual virus. While mostly recognized as an innate immune system function, our bodies do have active pattern recognition;
https://www.immunology.org/public-information/bitesized-immunology/receptors-and-molecules/pattern-recognition-receptor-prrs
Surely getting pounded over and over again with this disembodied single epitope from a non-conserved region is going to negatively affect our immune system's ability to learn the broader repertoire of proteins since those T-cells will get called up immediately upon a real infection in the transfected, while other learning will take time. Maybe this learning of other proteins gets drowned out to some extent because of this temporal delay.
Forget OAS... I do think it's a distraction. There is something new happening that is the result of these first-of-a-kind single epitope transfections that needs a new name. My gut is that the problem lies in a higher, pattern recognition function. Let's not please be so arrogant as to imagine that we fully understand the function of our immune systems - we are still trying to grasp higher level aspects as discussed in this modelling work;
https://journals.aps.org/prresearch/abstract/10.1103/PhysRevResearch.3.013222
Title: Understanding adaptive immune system as reinforcement learning
"The adaptive immune system of vertebrates can detect, respond to, and memorize diverse pathogens from past experience. While the clonal selection of T helper (Th) cells is the simple and established mechanism to better recognize new pathogens, the question that still remains unexplored is how the Th cells can acquire better ways to bias the responses of immune cells for eliminating pathogens more efficiently by translating the recognized antigen information into regulatory signals. In this work, we address this problem by associating the adaptive immune network organized by the Th cells with reinforcement learning (RL). By employing recent advancements of network-based RL, we show that the Th immune network can acquire the association between antigen patterns of and the effective responses to pathogens. Moreover, the clonal selection as well as other intercellular interactions are derived as a learning rule of the network. We also demonstrate that the stationary clone-size distribution after learning shares characteristic features with those observed experimentally. Our theoretical framework may contribute to revising and renewing our understanding of adaptive immunity as a learning system."
Another extract from the introduction of the same paper makes my point more clearly:
"Despite the availability of the latest experimental technologies, revealing the principles of such complex learning dynamics is still intricate because the immunological dynamics is shaped and organized by the collective interactions of
the entire immune cell population, which prevents us from simply reducing the problem down to the mere existence of specific cell types or molecules. "
Apologies if it appears aggressive, it's mostly that I have no idea why such an argument for the N protein lives on today when it shouldn't have started in the first place.
I will criticize how you frame your comment asking if they [those scientists] are wrong in their contention, mostly because we need to get away from the right/wrong paradigm. How do we define something as being right or wrong? In order to see if something is right, we need to see if the information and evidence that is being presented is accurate and substantiated. But at the point we look at the evidence then we don't need to argue if something is right or wrong, we need to argue if the evidence is there.
So it's not whether the scientists are wrong, but if their claims are substantiated from their work.
Ironically, I have criticized the author's recent work in one of my posts, which appears to be an update to their December post:
https://moderndiscontent.substack.com/p/about-the-immune-printing-study
The newest article here:
https://www.science.org/doi/10.1126/science.abq1841
This again is an example of a paper that appears to be circulating and being claimed to indicate that vaccines are causing immune imprinting, but there's many flaws with the methodology.
From those flaws I would argue that these researchers don't appear to have their claims substantiated by their results due to issues with their results.
As to a single antigen there are flu vaccines that only contain the HA antigen, but what makes this unique is the use of the body as the machinery to produce the spike which has possible ramifications.
Technically, there are likely to be conserved regions of the spike, but the receptor-binding domain is under constant selective pressure to mutate and that's usually considered the important region for sticking.
The general issue is that the entire immune system is complex- far more complex than the way it is taught and far more complex than how we've discussed it so there's plenty of things going on that either were not accounted for or that we have not known about before.
I absolutely commend your desire to learn more about all this! I will offer up a few suggestions to hone what you have already presented above:
Many vaccines do not use the whole organism whether it be bacterial or viral in nature. For example, Hepatitis B is a viral vaccine based on a surface antigen (however, it is the actual antigen and not mRNA so it would be more like Novavax, please see https://moderndiscontent.substack.com/p/all-roads-lead-to-spike-protein). And vaccines against the Tetanus and Diphtheria bacterium use inactivated toxins. Please also note that many of these vaccines have gone through several iterations before we got the gems we currently have. Just a side note as I am currently reading Dissolving Illusions about the smallpox vaccine and the parallels to our current predicament are rather alarming.
Also your comment "single disembodied epitope" isn't quite right. Think of the spike protein as your hand. When we produce antibodies against an antigen they will only present a small part of the antigen which is called an epitope. So you might form an antibody against the knuckle of your thumb and another against the tip of your ring finger. We all have unique HLA (molecules found on the surface of our cells which present pieces of antigens or epitopes found within the cell to immune systems cells). So we can all theoretically present different (to a certain degree) epitopes which can be used as models for antibodies i.e. my spike antibodies maybe different from your spike antibodies. There are examples of this in the supplemental material (table S4) from the first study you mentioned above. Please also see https://moderndiscontent.substack.com/p/about-the-immune-printing-study as both Brian & Modern Discontent have great discussion on this paper.
And your final point is spot on. I have learned so much this past year and there is nothing simple about the immune system - there's like a bazillion things going on at once. We attempt to simply things... but there is so much nuance needed. Best wishes in your continued learning!!
Wow, super link. Especially like the final quote.
Appreciation of our lack of understanding of the immune system is one reason I am reluctant to leap to any "this study says X is happening, and it shouldn't" stories, like "spike going to the nucleus" or "innate immune programming." These things are probably overblown. The IgG4 one was a really big exception!
So I agree with your first principles argument 100%. We shouldn't assume that a disembodied spike is an appropriate way to introduce a pattern recognition machine to a virus. How does it "know" that whatever protein the mRNA is coding is not pollen (allergic sensitization or tolerance) without the normal symphony of DAMPS from cells exploding with virus all over the place? It probably doesn't (though the "logic" of the structure of the spike may correct for this in some ways, like an APC still knows to focus on the receptor binding peptides for presentation). And now we see tolerance coming to roost.
RE "imprinting," which is just a rebranding of our regular understanding of immunity (https://unglossed.substack.com/i/65079519/4-is-immune-imprinting-any-different-from-the-current-understanding-of-b-cell-immunity) I disagree that it is important for vaccine strategy for SARS-CoV-2 *in practice* because there will never be a solution. Either we cut our losses and accept that getting sick is a part of life or we keep chasing the impossible dream of front-loading antibodies to future variants as if the immune system is as reprogrammable as a smartphone app. I think a lot of this is niche programmers trying to take over biology as a whole because they know they will be rewarded if their products fail to get results and non-programmers in science won't be able to critique them. "Imprinting" is a way to put immunology in their black box.
It is not in fact the case that "breakthrough" infections result in lower seroconversion against N - https://unglossed.substack.com/p/the-hot-spot#footnote-6 - Impressions to the contrary are an artifact of selection bias (the UK blood donor pool) or exclusive grading of early spring 2021 results (the Modern N antibodies paper). Further, OAS would not predict anything about N antibodies since those are unrelated to the spike protein encoded by the mRNA/DNA transfections.
Hmmm... my gut instinct remains that there is something afoot related to the vax pounding by a single epitope that does in fact impair the formation of broader immunity, of which N-protein antibodies would be a part. If we think about what is happening in the first days of a natural infection of a mRNA vax'ed person, they would have immediate recall of Wuhan-S, but it would take some time for the same person's immune system to learn N. Our immune systems did not evolve to do something useful with just one epitope from a given pathogen.. it's unnatural.
Is the UK blood donor pool related to the somewhat famous UK week 42 surveillance report where they admitted in writing that vax'ed were not displaying N-antibodies?
The same. And I commented at the time, 9 months ago, that it sounded like they simply weren't taking selection bias (infected less likely to donate) into account. Which is why the more rigorous sampling in Whitaker, H. et al. whih finds near-universal N-seroconversion is a better view of outcomes. So just as with this OAS review the main them is that published science spends most of its time in intellectual slacker mode.
The Covid vaccine don't prevent infection. That means they don't prevent the immune system from eventually encountering N protein. That means that the immune system has to somehow "know" that N protein and spike protein are part of the same entity to suppress a response to the former. It doesn't make much sense imo.
This is so true - I could not understand why people were jumping up and down over that graph. It is blood donors (of unknown infection status). From that graph you can see they were starting off with about 10% of the blood donor population being previously infected as S & N antibodies were similar. After the vax is rolled out S antibodies take off to nearly 100% (that was the point of the vaccine) while N antibodies slowly creep to 20%. What can you glean from the graph: even at week 42 people are still making N antibodies in spite of the fact that they were exposed to the vaccine. If we want to claim OAS then sample people infected after vaccination - did they make N antibodies or not. This graph is utterly useless other than to say that approximately 20% of blood donors as of week 42 had been infected & nearly 100% have been vaccinated. That's it. I made a comment on Alex's original post as I found the chart on page 25 much more useful (recovered persons were killing it on their antibody levels compared to the vaccinated over time). Sigh... thank you for your tireless work to try and get people to understand!
Thank you so much for taking the time to explain that! It leads to some interesting ideas, because if versions of Omicron persist, many people might continue to fall ill (who are vaccinated). It’s scary to think that then a lab or health agency 😳might consider releasing a new non-Wuhan wild type in order to help this subset of people recover.
I personally like the idea that Omicron was a purposeful lab leak (a well intentioned rogue lab) 😂 The whole idea of it being discovered with 4 foreigners traveling in Botswana(never identified) well it kind of sounds like intelligence agency stuff...
But what does it mean? I've noticed so much disagreement among those experts in virology. You'd think the immune system would have been figured out by now. The hubris of scientists who would tell us the introduction of strange things like trillions of spike proteins running loose in the body will save us because they know best. Unfortunately, what they know best seems to change over the years.
I would actually disagree. I think modernity has made us assume that we're near the end of science as we know it, but we're probably nowhere near the middle. Much of the scientific fields are still young relative to our history, and most certainly our modern history. I think this all comes down to science having a severe messaging problem where science has sold people the concept that they will be offered the moon when science has so many leaps to overcome before we even get near that point.
We're now seeing that these vaccines are causing people to think that some sort of mRNA vaccine is on the way now. Elon Musk's attempts to get to Mars has somehow made us believe that we're just a few years off before we all start engaging in space travel. I saw a recent segment from the Today Show where they were talking about this new monoclonal therapy for colorectal cancer that had 100% remission in the very small population that was given it. Did they discuss what they monoclonal therapy was, what genetic mutation it targeted, or anything such as that? No, the hosts started talking about how this means we're near defeating cancer when there's absolutely no way of knowing any of that from that tiny study and the grander complexity of cancer.
So I think we should remember that science is nowhere near figuring everything out, and with the immune system we are learning things that originally was part of the scientific consensus.
Heck, it was only a few years ago that researchers have found out that the innate immune system is actually trainable when it has been considered a static entity for decades!
I agree with everything you said. My problem with this whole vaccine issue, outside the fact that I and my family were hassled, especially early on for not taking the jab, for not accepting the words of known liars, was that it was politicized. I was told I was not being patriotic for refusing the vaccine. That was a message put out by the government and its media. As well as pushing fear. These are the words of Dr. Birx talking about what she knew early on, "I knew these vaccines were not going to protect against infection. And I think we overplayed the vaccines." Are those the words of someone who deserves trust? Who along with Fauci and the president said the vaccine will protect against infection and transmission. Fauci lied then. I doubt the president was in the loop, so he felt he was telling the truth. I've been taking certain things to protect me and I never got it despite rarely wearing a mask and being at concerts. Maybe my protocol worked, it's hard to say for sure. My entire family got Omicron and were mildly sick for around five days. They never got around to taking the Quecetin, D3, C, Zinc and NAC I've been on for many months. I would hope they are somewhat protected from having had it via acquired immunity. That was awhile ago, since then many of our vaccinated friends have had Omicron multiple times. Just anecdotal, but I like the fact I don't have trillions of spike proteins we were told would stay localized, but were later found having traveled throughout the body, with unknown consequences for the future. It simply comes down to a matter of trust. Big pharma and the government have not earned any trust whatsoever, especially when vast sums of money and control over the lives of many millions are involved.
OAS implies that the immune system is fundamentally unable to adapt, which makes no sense since memory immunity *is* plastic. OAS not being real means that the immune system can adapt.
Now that I can understand, but at this point of incredible scientific knowledge, why still all the studies, trials, tests to figure out what the heck is really going on? I honestly have lost faith in those studying this area of the complex systems of the human body. Mainly because many incredibly smart people claim that they finally figured it out, and the claims regularly contradict each other. What I'm trying to say is no one who reads this stuff can be sure, in fact it's not possible to be sure who is right, and that's kinda scary.