We've talked about this before, but this new imprint study does raise the question again why a previous vaccinated individual can produce new B-cells for the nucleus, but not unseen/changed parts of the spike protein.
One important aspect is that N-antibodies typically arrive only after one has cleared the infection. I mentioned this, as what was also left open is the question whether this reshuffle of existing B-cells only occurs if any older antibodies exist. As you have mentioned yourself 'AOS' is not a 'sin' as the old antibodies work fine. So there is also no need to create new ones.
But that would not mean, that if ever a new variant arrives in which the old types are all not effective, the body would not be able to create new B-cells. After all, that would result in large amounts of IgM's for proteins not seen before.
In fact we kind of know for sure that is the case. After all, what has been forgotten from the very early days of covid, is the research in how existing common cold immunity applied to covid. What was seen, is that we humans respond initially by producing large amounts of common cold antibodies, which are mostly non-effective (*). Still we all adapted back then, proving OAS wrong, as peopel infected then created Wuhan1 antibodies.
My guess is that the biochemical feedbacks causing a reshuffle vs produce new B-cells, only react this way when some effective response is mounted. But even then, the N-antibodies prove the body can learn and hence there must be a second factor at play here. I suggested that the changed spike sections may be too small or physically too close on the spikes to produce enough unique IgM's. Or other chemicals part of teh immune response interact here. (**). But I'm just speculating. It would hence be good to see, if truly no new B-cells are created for BA.1 unique proteins, even after a few months. We know also from early 2020 some people produce no antibodies at all, but did produce memory cells after beating covid.
*) There is one against the S2 protein that is, but only a minority of humans produces that. 2-4% in US/France, 10-15% in two African countries. But that is an interesting side issue.
**) The role of CD8 T+ cells is also interesting. Most of them are N-triggered, not spike triggered and may behave different, both in context of repeated infections as well as continuous boosting. This indicates separate learning mechanisms.
As far as N, the important thing is that memory immunity is not centralized, it is distributed. So there is no central "SARS-CoV-2 immune response." When nucleocapsid, membrane, envelope, and Orf1 proteins suddenly appear all over the place after infection, they are going to all be novel, so they will get taken by individual antigen presenting cells, become concentrated in individual lymph node germinal centers, where individual naive B Cells undergo affinity maturation and start to make effective B Cell receptors and antibodies.
Just the same as during true natural infection, here is a germinal center for spike, here is a separate one for this, for that. It's all "franchised." So there's no way to stop that from happening simply because previous spike B Cells are "masking" spike, because there's no central response to confuse or interfere with.
As for pre-existing coronavirus immunity, I think you have put it correctly. Maybe there is a bit of wire crossing but it's in no way close enough to SARS-CoV-2 to prevent a true "new virus" memory response. Otherwise how would we even have different human coronavirus antibodies to begin with. Or different flu (H1 vs H2 vs H3), where there has never been even a hint of antigen masking between the different HA species.
"It would hence be good to see, if truly no new B-cells are created for BA.1" It seems to be very close to none. Partly, this surprising result may be because all these mutant VOC spikes were not ever the product of immune escape. It remains totally a mystery to me to explain evolutionarily why they would exist outside of lab tinkering (without pulling the 'evolution is just mysterious' card).
"Most of them are N-triggered" That sounds like a reference to the recent Bartram post or to the original Campbell video it mentions https://bartram.substack.com/p/the-ukhsa-vaccine-surveillance-report-fe9 - however, this is about T Cells that are found to expand in people who avoid infections after exposure. So, the T Cell response after an infection and how that relates to natural immune protection might be different. But it is almost certain that tissue resident T Cells that can spot N protein in infected cells are going to help stop reinfection.
You are correct. And I knew that. Which is why it in fact is so puzzling. There is no central or intelligent immune system. It are all crude biochemical feedback mechanisms that control immunity.
Hence, that is why it is puzzling that your body does create a fresh new response against the nucleus, but not against the changed parts or a spike. What determines when it is changed vs new?
My guess is that as long as you mount some effective response, no new IgM's are created. After all, if existing CD4 T cell 'feelers' and hence also produced IgG's still 'stick', that *inherently* prevents antigen from being available to create IgM's. Evolutionary that would make sense, as the less effective the old antibodies are, the more antigen 'stay available' and the more IgM's will be created. And that in term is what causes new B-cells and new IgG's to be created. So when old antibodies are effective, the body will not bother to produce new, but at the same time OAS will not occur and you will mount a response when the virus has mutated enough.
And hence also, since vaccination causes no N-response, you will create it when first exposed to the real thing. But existing CD4/IgG's still neutralize spike, and hence no new B-cells are needed/created for the spike despite that it has mutated somewhat.
Last, in terms of CD8, I was not responding to Campbell or Bartram. (I don't even know what you are referring to, so you made me curious. I'll have to go look now ...) I'm however referring to some early 2021 research, when comparing natural immunity vs vaccine immunity was still allowed, and possible to be published. (Later in 2021 that would inherently demonstrate the 'why' vaccines failed and became a non-discussable topic.) But early research showed two important things. Foremost that most CD8 T cells are N-trigered. This is interesting as their CD4 siblings are dominantly spike-trigered. So there is a different 'learning' mechanic at work here. That is what I was referring too. (But thinking about it more, the mechanism of older antibodies still 'sticking' and hence keeping antigens from creating IgM's explains it probably well enough.)
(Second finding, not relevant here, but still interesting is Pfizer vaccine produces little to no CD8 in many studies. There is some conflicting data here among different studies, probably depending on cohort and time of measurement, but consensus among all, seems to be that it produces *far* less CD8 T cells than natural immunity. One study showed no CD8 production at all after one shot and only 40% of participants after the 2nd. But the same study found 100% of J&J vaccine takers had CD8 production after their single shot. This also matched their respective trial data, where J&J did better on CD8 than mRNA. This seems to indicate again the delivery mechanism matters, just as for IgG4 AstraZeneca vs mRNA matters.)
OAS is a pair of claims and both are expressed as absolute maxims that never have any exception. In other words, OAS is only true if it is not possible for the claims not to happen. One is "childhood / first antibodies highest" and the other is "imprinting." Both have been refuted with flu as far as being absolute maxims.
The level of neutralization is equal between BA.1 and Wuhan in Quandt, et al. This refutes "first antibodies highest" But those balanced antibodies are made from the original B Cell pool. So the first part of OAS is wrong because the second part of OAS is right.
*and the reason one sounds deceptive and shifty when explaining why OAS is not true is because when you read all the original use Francis is making this big, stupid mixed bag of claims. So it's like explaining why some kooky economic theory isn't true just because one part of it is true.
Rather disappointed in Kirsch. He has a good head for business and PR type things but no head for sussing out the truth as far as I can tell.
I'm just skeptical that any count of who died and when will ever produce a meaningful signal. What has to happen is looking at actual people or corpses and finding out what happened. Bob died on Tuesday will never be a strong argument for what killed Bob.
I suspect so. If I understand it right the spike sort of does random vascular damage. So if it does small amounts of damage in big arteries it could take a long time to show up. But if it does damage in capillaries in brain or damage to heart tissue it shows up as myocarditis or microstrokes fairly quickly.
But there are so many dangerous mechanisms of action for the shot, I think for the actual virus the spike is most of the problem. The chronic heavy hitters may be very different from the acute heavy hitters.
I'd say Steve's proof has failed to survive review by peers ...
And I can't make head or tail out of his new computation - it would be good if he provided an XLS worksheet or working code to download instead of some arbitrary "hand-waving" description in English :)
Funny - I like the whole "try to figure out what he does at each step by re-producing the result" part of the process. It helps me think about the problem
That's why I worked with by-month rates for both compiles, to get a feel for those type of artifacts. And it's not hard to create adjusted alive / observed values by subtracting the immortal days. (Kirsch, in contrast, has done "repeat the design but with a different start date" checks which doesn't do anything to test the design.) And then you aren't going to find anything of course, because you no longer have something to compare to. It's just to show that the comparison was an illusion created by the penalty all along. Was the thing being penalized immortal time bias, or just that we already know that the vaccinated died more in 2022 because of Omicron? There's no actual way to tell.
Right - but I think the difference is simply that you have shown in your generously thorough comment on Kirsch's post what *could* be done to find a signal* - whereas I am just interested in deconstruction of his method
*But still imperiled by the exogenous threats of cherry-picking / publication bias. And in general I whip out the tongs for anything in the self-control design mode, which is what that kind of early vs. late rate design would be. But it was extremely well described and defined in your comment.
We've talked about this before, but this new imprint study does raise the question again why a previous vaccinated individual can produce new B-cells for the nucleus, but not unseen/changed parts of the spike protein.
One important aspect is that N-antibodies typically arrive only after one has cleared the infection. I mentioned this, as what was also left open is the question whether this reshuffle of existing B-cells only occurs if any older antibodies exist. As you have mentioned yourself 'AOS' is not a 'sin' as the old antibodies work fine. So there is also no need to create new ones.
But that would not mean, that if ever a new variant arrives in which the old types are all not effective, the body would not be able to create new B-cells. After all, that would result in large amounts of IgM's for proteins not seen before.
In fact we kind of know for sure that is the case. After all, what has been forgotten from the very early days of covid, is the research in how existing common cold immunity applied to covid. What was seen, is that we humans respond initially by producing large amounts of common cold antibodies, which are mostly non-effective (*). Still we all adapted back then, proving OAS wrong, as peopel infected then created Wuhan1 antibodies.
My guess is that the biochemical feedbacks causing a reshuffle vs produce new B-cells, only react this way when some effective response is mounted. But even then, the N-antibodies prove the body can learn and hence there must be a second factor at play here. I suggested that the changed spike sections may be too small or physically too close on the spikes to produce enough unique IgM's. Or other chemicals part of teh immune response interact here. (**). But I'm just speculating. It would hence be good to see, if truly no new B-cells are created for BA.1 unique proteins, even after a few months. We know also from early 2020 some people produce no antibodies at all, but did produce memory cells after beating covid.
*) There is one against the S2 protein that is, but only a minority of humans produces that. 2-4% in US/France, 10-15% in two African countries. But that is an interesting side issue.
**) The role of CD8 T+ cells is also interesting. Most of them are N-triggered, not spike triggered and may behave different, both in context of repeated infections as well as continuous boosting. This indicates separate learning mechanisms.
As far as N, the important thing is that memory immunity is not centralized, it is distributed. So there is no central "SARS-CoV-2 immune response." When nucleocapsid, membrane, envelope, and Orf1 proteins suddenly appear all over the place after infection, they are going to all be novel, so they will get taken by individual antigen presenting cells, become concentrated in individual lymph node germinal centers, where individual naive B Cells undergo affinity maturation and start to make effective B Cell receptors and antibodies.
Just the same as during true natural infection, here is a germinal center for spike, here is a separate one for this, for that. It's all "franchised." So there's no way to stop that from happening simply because previous spike B Cells are "masking" spike, because there's no central response to confuse or interfere with.
As for pre-existing coronavirus immunity, I think you have put it correctly. Maybe there is a bit of wire crossing but it's in no way close enough to SARS-CoV-2 to prevent a true "new virus" memory response. Otherwise how would we even have different human coronavirus antibodies to begin with. Or different flu (H1 vs H2 vs H3), where there has never been even a hint of antigen masking between the different HA species.
"It would hence be good to see, if truly no new B-cells are created for BA.1" It seems to be very close to none. Partly, this surprising result may be because all these mutant VOC spikes were not ever the product of immune escape. It remains totally a mystery to me to explain evolutionarily why they would exist outside of lab tinkering (without pulling the 'evolution is just mysterious' card).
"Most of them are N-triggered" That sounds like a reference to the recent Bartram post or to the original Campbell video it mentions https://bartram.substack.com/p/the-ukhsa-vaccine-surveillance-report-fe9 - however, this is about T Cells that are found to expand in people who avoid infections after exposure. So, the T Cell response after an infection and how that relates to natural immune protection might be different. But it is almost certain that tissue resident T Cells that can spot N protein in infected cells are going to help stop reinfection.
You are correct. And I knew that. Which is why it in fact is so puzzling. There is no central or intelligent immune system. It are all crude biochemical feedback mechanisms that control immunity.
Hence, that is why it is puzzling that your body does create a fresh new response against the nucleus, but not against the changed parts or a spike. What determines when it is changed vs new?
My guess is that as long as you mount some effective response, no new IgM's are created. After all, if existing CD4 T cell 'feelers' and hence also produced IgG's still 'stick', that *inherently* prevents antigen from being available to create IgM's. Evolutionary that would make sense, as the less effective the old antibodies are, the more antigen 'stay available' and the more IgM's will be created. And that in term is what causes new B-cells and new IgG's to be created. So when old antibodies are effective, the body will not bother to produce new, but at the same time OAS will not occur and you will mount a response when the virus has mutated enough.
And hence also, since vaccination causes no N-response, you will create it when first exposed to the real thing. But existing CD4/IgG's still neutralize spike, and hence no new B-cells are needed/created for the spike despite that it has mutated somewhat.
Last, in terms of CD8, I was not responding to Campbell or Bartram. (I don't even know what you are referring to, so you made me curious. I'll have to go look now ...) I'm however referring to some early 2021 research, when comparing natural immunity vs vaccine immunity was still allowed, and possible to be published. (Later in 2021 that would inherently demonstrate the 'why' vaccines failed and became a non-discussable topic.) But early research showed two important things. Foremost that most CD8 T cells are N-trigered. This is interesting as their CD4 siblings are dominantly spike-trigered. So there is a different 'learning' mechanic at work here. That is what I was referring too. (But thinking about it more, the mechanism of older antibodies still 'sticking' and hence keeping antigens from creating IgM's explains it probably well enough.)
(Second finding, not relevant here, but still interesting is Pfizer vaccine produces little to no CD8 in many studies. There is some conflicting data here among different studies, probably depending on cohort and time of measurement, but consensus among all, seems to be that it produces *far* less CD8 T cells than natural immunity. One study showed no CD8 production at all after one shot and only 40% of participants after the 2nd. But the same study found 100% of J&J vaccine takers had CD8 production after their single shot. This also matched their respective trial data, where J&J did better on CD8 than mRNA. This seems to indicate again the delivery mechanism matters, just as for IgG4 AstraZeneca vs mRNA matters.)
==> The mRNA-vaccinated appear to be stuck with their original B Cell pool forever. But it’s ok.
Is that kind of, sort of like original antigenic sin?
OAS is a pair of claims and both are expressed as absolute maxims that never have any exception. In other words, OAS is only true if it is not possible for the claims not to happen. One is "childhood / first antibodies highest" and the other is "imprinting." Both have been refuted with flu as far as being absolute maxims.
The level of neutralization is equal between BA.1 and Wuhan in Quandt, et al. This refutes "first antibodies highest" But those balanced antibodies are made from the original B Cell pool. So the first part of OAS is wrong because the second part of OAS is right.
*and the reason one sounds deceptive and shifty when explaining why OAS is not true is because when you read all the original use Francis is making this big, stupid mixed bag of claims. So it's like explaining why some kooky economic theory isn't true just because one part of it is true.
Rather disappointed in Kirsch. He has a good head for business and PR type things but no head for sussing out the truth as far as I can tell.
I'm just skeptical that any count of who died and when will ever produce a meaningful signal. What has to happen is looking at actual people or corpses and finding out what happened. Bob died on Tuesday will never be a strong argument for what killed Bob.
Right, that's how I feel. Anyway I still think there's tons of heart damage still to be "cashed in." Tip of the iceberg could be the correct paradigm.
I suspect so. If I understand it right the spike sort of does random vascular damage. So if it does small amounts of damage in big arteries it could take a long time to show up. But if it does damage in capillaries in brain or damage to heart tissue it shows up as myocarditis or microstrokes fairly quickly.
But there are so many dangerous mechanisms of action for the shot, I think for the actual virus the spike is most of the problem. The chronic heavy hitters may be very different from the acute heavy hitters.
Off-topic:
Jonathan Couey is underwhelmed with Brian Mowrey's attitude and wants a parlay on his twitch show.
https://www.twitch.tv/videos/1727033554
cue: 00:06:15 -> 00:17:10
Note: This commenter likes to watch scientists arguing as if they were scientists.
First of all, I would like to make it clear, that at no point in life have I ever been praised for my attitude.
LOL
That's the correct attitude, actually.
Best things I've read this week:
https://live2fightanotherday.substack.com/p/japan-jabbination-progress
https://live2fightanotherday.substack.com/p/disappearing-benefits-of-covid-countermeasures
Comments fixed back to everyone. Stupid substack defaults
I'd say Steve's proof has failed to survive review by peers ...
And I can't make head or tail out of his new computation - it would be good if he provided an XLS worksheet or working code to download instead of some arbitrary "hand-waving" description in English :)
Funny - I like the whole "try to figure out what he does at each step by re-producing the result" part of the process. It helps me think about the problem
That's why I worked with by-month rates for both compiles, to get a feel for those type of artifacts. And it's not hard to create adjusted alive / observed values by subtracting the immortal days. (Kirsch, in contrast, has done "repeat the design but with a different start date" checks which doesn't do anything to test the design.) And then you aren't going to find anything of course, because you no longer have something to compare to. It's just to show that the comparison was an illusion created by the penalty all along. Was the thing being penalized immortal time bias, or just that we already know that the vaccinated died more in 2022 because of Omicron? There's no actual way to tell.
Right - but I think the difference is simply that you have shown in your generously thorough comment on Kirsch's post what *could* be done to find a signal* - whereas I am just interested in deconstruction of his method
*But still imperiled by the exogenous threats of cherry-picking / publication bias. And in general I whip out the tongs for anything in the self-control design mode, which is what that kind of early vs. late rate design would be. But it was extremely well described and defined in your comment.