This is an eminently testable hypothesis that can be explored by examining regulatory T-cell responses (or other immune tolerance responses) following vaccination. To date, I can find no evidence that anyone has done this, but I would hope that it will happen in the near future, and the results will be illuminating.
This is an eminently testable hypothesis that can be explored by examining regulatory T-cell responses (or other immune tolerance responses) following vaccination. To date, I can find no evidence that anyone has done this, but I would hope that it will happen in the near future, and the results will be illuminating.
Tolerance is not an on/off phenomenon but rather a wide spectrum ranging from the complete immune acceptance of most of our own proteins to the extreme reactogenicity of a serious peanut or bee sting allergy. Tolerance mechanisms can coexist with immunity mechanisms, such that tolerance begins to become apparent as the level of neutralizing antibodies declines. And to be clear, I am not hypothesizing that the genetic Covid-19 vaccines function by virtue of inducing tolerance. It has been well-demonstrated that they induce a strong neutralizing antibody response. I am instead suggesting that they may *also* be inducing partial tolerance, and that this effect may help to explain strong protection against severe (immune overreaction) disease, high rates of illness transmission in high-vax areas, and possibly also significant declines in immunity after 4-6 months despite continuing high antibody levels.
If indeed the genetic Covid-19 vaccines are inducing partial tolerance, we can make certain predictions:
1. Genetic vaccines will be extremely effective at preventing severe disease, but much less effective in terms of preventing infection. (True)
2. As vaccine immunity wanes, protection against cytokine-storm-type severe disease will be maintained. (Seems to be true)
3. As vaccine immunity wanes, vaccinated people will increasingly carry and spread the virus, and population-level viral prevalence will rise in areas with a high uptake of genetic vaccines. (True) Vaccinated people will be more likely to be asymptomatic carriers. (True, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00460-6/fulltext)
4. This will lead to a significant wave of illness transmission which will disproportionately affect unvaccinated people (who are not protected against severe disease). (True right now across the US and much of the world)
5. Booster shots will further increase tolerance, leading to an increased level of disease prevalence across the population. (True in Israel)
6. As immunity wanes and new antibody-resistant variants emerge, vaccinated people will be more vulnerable to long-term/chronic infection with high viral loads. Due to the protective effects of tolerance this will likely manifest not as typical severe Covid-19 illness (pneumonia, ventilators, cytokine storms, multiorgan failure) but rather as spike protein toxicity. So we should watch for an increase in clotting, strokes, heart attacks, myocarditis, neurological problems, etc. Vaccinated patients dying of these conditions may not be tested for Covid-19 and so likely will not be counted as covid deaths, and the myth of vaccine efficacy may persist based on the original definition of “preventing severe Covid-19 disease” even as we experience a wave of mysterious illness and death. Furthermore, vaccinated people may be more vulnerable to other infections due to regulatory-T-cell mediated general immune suppression. Should ADE develop, with non-neutralizing antibodies facilitating enhanced infection or direct infection of immune cells, tolerance could well lead to further exacerbation. However tolerance could also provide protection against cytokine storm-type reactions and accelerate the evolution of SARS-CoV2 into an endemic human pathogen, so the long-term effect of tolerance is uncertain.
7. Contrary to the shrill claims of the fearful, vaccinated people will present a much greater danger than unvaccinated people in terms of asymptomatic transmission and evolution of new variants.
8. There are likely to be significant differences between the vaccines. In particular, the two-shot series would be expected to induce greater tolerance, and possibly also greater tolerance will be evident in countries with a shorter interval between the two shots. Countries that utilized inactivated-virus vaccines are probably less likely to see tolerance effects, although they may still encounter ADE or other problems down the road.
This hypothesis presents a scenario of vaccine failure that first appears as success (because tolerance prevents severe disease), that explains the trends currently observed (unexpectedly high illness rates in high-vax areas), and that potentially portends a troubling future without invoking the still-hypothetical ADE.
Hm... Tolerance is still not wholesale immunocompromise. I don't see how even with spike tolerance you get to viremia without inflammation from the cellular destruction; plus there's immunogenic N proteins etc. There's so many other signals besides the spike protein. It should still lead to pneumonia. Not sure if that makes it same problem or worse; can't make it better.
Moreover, while I totally agree with your framing of the blended immune response, I don't think it leads to boosters causing the blend to *shift* in favor of tolerance. The cycle of ramped-up antibodies, gradually recovering cellular immunity (after being depleted to clean up mRNA-generated spike), then infection, just goes on forever.
You have convinced me of one thing - for the unvaccinated, there could essentially no longer be "waves" of higher exposure to SC2.
But I'm not worried about that making us sick more in annual rates (maybe just a one-time elevation throughout autumn). Problem is, respiratory viruses are supposed to be seasonal. Now you have me worried that the real tolerance threat will be among the unvaccinated, whose immune response just switches off at a certain point due to literally constant exposure (that's on top of the scary possibility of the vaccinated somehow expressing spike, and what kind of immune response that is generating).
"Hm... Tolerance is still not wholesale immunocompromise. I don't see how even with spike tolerance you get to viremia without inflammation from the cellular destruction; plus there's immunogenic N proteins etc. There's so many other signals besides the spike protein. It should still lead to pneumonia. Not sure if that makes it same problem or worse; can't make it better."
That's a good point. Tolerance should not prevent illness. However if it blocks the ADE-like cytokine storm that is characteristic of severe Covid-19 we might see a clinically-different presentation of severe illness - vascular damage or some other symptom might become critical before the appearance of pneumonia and low O2 saturation.
"Moreover, while I totally agree with your framing of the blended immune response, I don't think it leads to boosters causing the blend to *shift* in favor of tolerance. The cycle of ramped-up antibodies, gradually recovering cellular immunity (after being depleted to clean up mRNA-generated spike), then infection, just goes on forever."
That depends on how rapidly tolerance decays relative to antibody declines - and/or whether tolerance reaches a level at which it can no longer be "boosted." A perpetual cycle as you suggest seems equally plausible.
"Now you have me worried that the real tolerance threat will be among the unvaccinated, whose immune response just switches off at a certain point due to literally constant exposure."
As long as the virus still causes an adaptive immune response (i.e. against N protein) in the vaccinated and is eventually cleared, there should still be waves - although the temporal dynamics of the waves might change. Also I'm not convinced that constant exposure to an infectious virus to which one has immunity is likely to induce tolerance and loss of immunity. To my knowledge this didn't happen e.g. to doctors who spent their careers treating acute Tb or polio patients with constant high-level exposure.
Thanks for engaging with this hypothesis. I've had a sense lately that even the "alternative" sources are missing something important, but I don't have the audience to be heard, and I'm far from sure I'm correct either.
Here's a scary thought: This is exactly the sort of thing that might result from an genetic vaccine-induced tolerance response. If millions of cells suddenly have an altered proteome - expressing spike protein and generating an auto-attack immune response - then the immune tolerance mechanisms are going to send a message to the killer CD8 cells: "Stop killing cells with altered proteomes." Which could easily lead to a situation in which cancer cells slip past the immune system. We'll have to see if other doctors start reporting a similar uptick in cancers.
That's a good point - not just doctors but all of us are constantly harboring "pathogenic" bacteria, that are easily kept in check as long as there is good microbiome health, and constantly reencountering polio and other enteroviruses.
Since SARS-CoV-2 also replicates in the gut, it is simultaneously being overseen by our most sophisticated "immune lab."
I still worry. My neanderthal immunology default is always, "Mess with the natural pattern, mess up the immune response."
Cancer via tolerance, or cellular immunity exhaustion - either seems mistakable for the other in the short term. Tolerance could imply a much worse long term result, though - perpetual cancer formation, system wide.
Continued...
This is an eminently testable hypothesis that can be explored by examining regulatory T-cell responses (or other immune tolerance responses) following vaccination. To date, I can find no evidence that anyone has done this, but I would hope that it will happen in the near future, and the results will be illuminating.
Tolerance is not an on/off phenomenon but rather a wide spectrum ranging from the complete immune acceptance of most of our own proteins to the extreme reactogenicity of a serious peanut or bee sting allergy. Tolerance mechanisms can coexist with immunity mechanisms, such that tolerance begins to become apparent as the level of neutralizing antibodies declines. And to be clear, I am not hypothesizing that the genetic Covid-19 vaccines function by virtue of inducing tolerance. It has been well-demonstrated that they induce a strong neutralizing antibody response. I am instead suggesting that they may *also* be inducing partial tolerance, and that this effect may help to explain strong protection against severe (immune overreaction) disease, high rates of illness transmission in high-vax areas, and possibly also significant declines in immunity after 4-6 months despite continuing high antibody levels.
If indeed the genetic Covid-19 vaccines are inducing partial tolerance, we can make certain predictions:
1. Genetic vaccines will be extremely effective at preventing severe disease, but much less effective in terms of preventing infection. (True)
2. As vaccine immunity wanes, protection against cytokine-storm-type severe disease will be maintained. (Seems to be true)
3. As vaccine immunity wanes, vaccinated people will increasingly carry and spread the virus, and population-level viral prevalence will rise in areas with a high uptake of genetic vaccines. (True) Vaccinated people will be more likely to be asymptomatic carriers. (True, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00460-6/fulltext)
4. This will lead to a significant wave of illness transmission which will disproportionately affect unvaccinated people (who are not protected against severe disease). (True right now across the US and much of the world)
5. Booster shots will further increase tolerance, leading to an increased level of disease prevalence across the population. (True in Israel)
6. As immunity wanes and new antibody-resistant variants emerge, vaccinated people will be more vulnerable to long-term/chronic infection with high viral loads. Due to the protective effects of tolerance this will likely manifest not as typical severe Covid-19 illness (pneumonia, ventilators, cytokine storms, multiorgan failure) but rather as spike protein toxicity. So we should watch for an increase in clotting, strokes, heart attacks, myocarditis, neurological problems, etc. Vaccinated patients dying of these conditions may not be tested for Covid-19 and so likely will not be counted as covid deaths, and the myth of vaccine efficacy may persist based on the original definition of “preventing severe Covid-19 disease” even as we experience a wave of mysterious illness and death. Furthermore, vaccinated people may be more vulnerable to other infections due to regulatory-T-cell mediated general immune suppression. Should ADE develop, with non-neutralizing antibodies facilitating enhanced infection or direct infection of immune cells, tolerance could well lead to further exacerbation. However tolerance could also provide protection against cytokine storm-type reactions and accelerate the evolution of SARS-CoV2 into an endemic human pathogen, so the long-term effect of tolerance is uncertain.
7. Contrary to the shrill claims of the fearful, vaccinated people will present a much greater danger than unvaccinated people in terms of asymptomatic transmission and evolution of new variants.
8. There are likely to be significant differences between the vaccines. In particular, the two-shot series would be expected to induce greater tolerance, and possibly also greater tolerance will be evident in countries with a shorter interval between the two shots. Countries that utilized inactivated-virus vaccines are probably less likely to see tolerance effects, although they may still encounter ADE or other problems down the road.
This hypothesis presents a scenario of vaccine failure that first appears as success (because tolerance prevents severe disease), that explains the trends currently observed (unexpectedly high illness rates in high-vax areas), and that potentially portends a troubling future without invoking the still-hypothetical ADE.
Hm... Tolerance is still not wholesale immunocompromise. I don't see how even with spike tolerance you get to viremia without inflammation from the cellular destruction; plus there's immunogenic N proteins etc. There's so many other signals besides the spike protein. It should still lead to pneumonia. Not sure if that makes it same problem or worse; can't make it better.
Moreover, while I totally agree with your framing of the blended immune response, I don't think it leads to boosters causing the blend to *shift* in favor of tolerance. The cycle of ramped-up antibodies, gradually recovering cellular immunity (after being depleted to clean up mRNA-generated spike), then infection, just goes on forever.
You have convinced me of one thing - for the unvaccinated, there could essentially no longer be "waves" of higher exposure to SC2.
But I'm not worried about that making us sick more in annual rates (maybe just a one-time elevation throughout autumn). Problem is, respiratory viruses are supposed to be seasonal. Now you have me worried that the real tolerance threat will be among the unvaccinated, whose immune response just switches off at a certain point due to literally constant exposure (that's on top of the scary possibility of the vaccinated somehow expressing spike, and what kind of immune response that is generating).
"Hm... Tolerance is still not wholesale immunocompromise. I don't see how even with spike tolerance you get to viremia without inflammation from the cellular destruction; plus there's immunogenic N proteins etc. There's so many other signals besides the spike protein. It should still lead to pneumonia. Not sure if that makes it same problem or worse; can't make it better."
That's a good point. Tolerance should not prevent illness. However if it blocks the ADE-like cytokine storm that is characteristic of severe Covid-19 we might see a clinically-different presentation of severe illness - vascular damage or some other symptom might become critical before the appearance of pneumonia and low O2 saturation.
"Moreover, while I totally agree with your framing of the blended immune response, I don't think it leads to boosters causing the blend to *shift* in favor of tolerance. The cycle of ramped-up antibodies, gradually recovering cellular immunity (after being depleted to clean up mRNA-generated spike), then infection, just goes on forever."
That depends on how rapidly tolerance decays relative to antibody declines - and/or whether tolerance reaches a level at which it can no longer be "boosted." A perpetual cycle as you suggest seems equally plausible.
"Now you have me worried that the real tolerance threat will be among the unvaccinated, whose immune response just switches off at a certain point due to literally constant exposure."
As long as the virus still causes an adaptive immune response (i.e. against N protein) in the vaccinated and is eventually cleared, there should still be waves - although the temporal dynamics of the waves might change. Also I'm not convinced that constant exposure to an infectious virus to which one has immunity is likely to induce tolerance and loss of immunity. To my knowledge this didn't happen e.g. to doctors who spent their careers treating acute Tb or polio patients with constant high-level exposure.
Thanks for engaging with this hypothesis. I've had a sense lately that even the "alternative" sources are missing something important, but I don't have the audience to be heard, and I'm far from sure I'm correct either.
I came across this from another comment here:
https://www.lifesitenews.com/news/idaho-doctor-reports-a-20-times-increase-of-cancer-in-vaccinated-patients/?utm_source=wnd&utm_medium=wnd&utm_campaign=syndicated
Here's a scary thought: This is exactly the sort of thing that might result from an genetic vaccine-induced tolerance response. If millions of cells suddenly have an altered proteome - expressing spike protein and generating an auto-attack immune response - then the immune tolerance mechanisms are going to send a message to the killer CD8 cells: "Stop killing cells with altered proteomes." Which could easily lead to a situation in which cancer cells slip past the immune system. We'll have to see if other doctors start reporting a similar uptick in cancers.
That's a good point - not just doctors but all of us are constantly harboring "pathogenic" bacteria, that are easily kept in check as long as there is good microbiome health, and constantly reencountering polio and other enteroviruses.
Since SARS-CoV-2 also replicates in the gut, it is simultaneously being overseen by our most sophisticated "immune lab."
I still worry. My neanderthal immunology default is always, "Mess with the natural pattern, mess up the immune response."
Cancer via tolerance, or cellular immunity exhaustion - either seems mistakable for the other in the short term. Tolerance could imply a much worse long term result, though - perpetual cancer formation, system wide.
IMO ADE is not the thing to worry about. it is ADH
What is ADH?
antibody dependent hypersensitivty