Brian Mowrey has more or less convinced me that my original idea that tolerance is protective against severe infection/cytokine storms is probably wrong, and I must credit my original investigation of the idea to a twitter post by Robert Malone, but overall the hypothesis seems to be holding up. I'm frankly surprised that the idea that sneaking genetic code into otherwise healthy cells, thus causing them to make a foreign protein and get attacked in the absence of any other markers of infection, would likely lead to tolerance did not occur to a wider group of people earlier on.
An mRNA vaccine has even been specifically developed to *induce* tolerance, and the differences in inflammatory vs. non-inflammatory lipid packaging that supposedly make all the difference are far from convincing to me: https://www.nature.com/articles/s41587-021-00880-0
It is possible that you did not get some MINOR details right, but you got the MAJOR ideas right. (who is always right about everything predicting the future? Not me either) I mentioned that June post of mine, referring to you, a few times recently so that your idea would get credit.
I find this topic of immune tolerance to be fascinating. Glad we crossed our paths.
1. It’s a good study, but still only one (https://www.science.org/doi/10.1126/sciimmunol.ade2798). They validated their findings using quite a few different approaches. I do not doubt their findings with regard to a dramatic increase in anti-inflammatory IgG4 spike antibodies after multiple mRNA vaccinations, but it would be helpful to see it replicated.
2. The link between IgG4 tolerance and negative vaccine efficacy remains to be proven. We don’t yet have a direct correlation between IgG4 antibody levels and risk or severity of infection.
3. There are other potential explanations for negative vaccine efficacy. Among these are a) Antibody-Dependent Enhancement of Infection (ADEI), wherein the antibody response facilitates rather than inhibits infection, b) a broader-scale immune reprogramming/depletion induced by vaccination (e.g. https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v1), or c) a simple game of catch-up, given that the most-vaccinated people are still the least likely to have been infected to date (whether due to early vaccine efficacy or simply to being the most careful to avoid situations where viral spread is likely) (https://unglossed.substack.com/p/of-course-the-uber-boosted-are-the).
4. Despite these caveats, I think that tolerance is real and is contributing to the current high level of covid infections and excess deaths.
5. We should collectively have anticipated tolerance as a likely risk of repeated genetic vaccination. As Brian Mowrey writes: “…using host cells to produce a foreign antigen, absent associated molecular markers of viral infection, intrinsically risks tolerance: The immune system must associate spike protein with “self.”” (https://unglossed.substack.com/p/tolerance-maims-and-kills-potential) Developers of mRNA vaccines are not oblivious to this; they have even successfully developed a *tolerance-inducing* mRNA vaccine in mice: https://www.nature.com/articles/s41587-021-00880-0
6. Tolerance is probably mostly an mRNA thing. It is almost certainly going to be specific to *genetic* vaccinations, in which the body attacks its own cells serving as antigen factories rather than some injected particles carrying the antigens. The authors of the study found almost no IgG4 antibodies in people who had received a lifetime of tetanus vaccinations. It also appears to be substantially lower with the viral vector genetic vaccines, at least according to the one study published so far. This may be related to a lower spike dose and shorter duration of spike exposure, which correlates with a lower rate of post-vaccination fever and illness. The viral vector vaccines also generate antibodies against the vector itself, which makes boosters less likely to make it past the body’s defenses to generate spike protein.
7. Tolerance requires multiple exposures. It is unlikely to develop after a single shot; in fact, the second shot typically elicits a more severe reaction since the immune system was primed (rendered *less* tolerant) by the first one.
8. Tolerance is the inverse of reactivity. People who experienced a significant acute reaction to their second shot (high fever, body aches, etc.) but a more subdued reaction to their third and later shots are most likely developing some degree of spike tolerance.
9. Reactivity can probably induce tolerance. Given that there are no actual viruses or other signatures of infection present, it is likely that the “intelligence arm” of the immune system perceives the reactive, inflammatory response to the second dose as a mistake – along the lines of an overreaction to a bee sting. This will tend to lead to development of tolerance over time, particularly with additional exposures. Thus the fact that the mRNA shots make most people sicker than any other vaccination in common use is likely related to their propensity to induce tolerance.
10. There will likely be a wide range of individual variability in tolerance, despite identical exposures. This is true in the allergy world, e.g. with bee stings and responses to allergy shots. Individual immune responses vary widely, especially when it comes to tolerance vs. reactivity to a particular antigen following a particular pattern of exposure.
11. IgG4 tolerance is not “VAIDS” or broader-scale immunodeficiency. I don’t like “VAIDS” as a term. AIDS is a specific condition caused by progressive infection and destruction of CD4+ T-cells by HIV. Whatever might be occurring with immunodeficiency in the current context, it isn’t that, and so the effects will be different. I also don’t agree with Rintrah’s reasoning that tolerance to covid spike will equate to tolerance to flu and other viruses because viruses share functional parts (https://www.rintrah.nl/the-trainwreck-of-all-trainwrecks-billions-of-people-stuck-with-a-broken-immune-response/). Antibodies are sufficiently *specific* in their binding (even losing binding ability with mutations in the same virus), and respiratory viruses are sufficiently different, that this should not be a thing.
12. If covid infection leads to general immunodeficiency, then IgG4 tolerance may cause general immunodeficiency *indirectly*. This could occur due to frequent or chronic infection with SARS-CoV2 as a result of spike tolerance, assuming that infection is at least temporarily immunosuppressive as has been suggested and as is true also with measles.
13. mRNA vaccination may also directly cause general immunodeficiency or a reprogramming of immune response leading to a weaker response toward some targets like fungi or cancer cells. There are some hints in this direction, and it is reasonable to hypothesize that the immune system might respond to the self-attack induced by mRNA vaccination by broadly suppressing activity. This would however be a different mechanism than IgG4 tolerance and remains to be thoroughly investigated. It is even possible that the development of *specific* IgG4 tolerance over time might allow the immune system to relax its more *general* immunosuppressive tolerance in the context of continuing mRNA vaccination.
14. The negative effects of spike tolerance are likely to be mediated through failure to resist infection, toxicity of cumulative spike exposure, and direct viral tissue damage due to higher viral loads and longer duration of infection. If specific IgG4 tolerance is taking effect in the multiply-boosted, we would expect to see people getting infected with SARS-CoV2 more often, suffering more severe infections, taking longer to clear the virus, and suffering more cardiac complications linked to spike exposure. As noted above, though, tolerance is not the *only* hypothesis that could explain these things.
15. I would expect tolerance to be much more of a concern in the boosted (and especially the multiply-boosted) than in people who just received an original mRNA vaccination series. This is borne out to a limited extent by the fact that breakthrough infection substantially amplified IgG4 antibodies in the boosted but much less so in people who had only received the initial series (Fig. S8 of the linked study).
I agree on all these points except 1) I'm leaning back toward skepticism that AIDS is a sui generis viral etiology (ie the HIV > AIDS theory being valid), so I don't think the bar is necessarily very high for "VAIDS" to be a valid term. 2) I think the tetanus results confirmed IgG4 from repeat toxoid injection, there's just high variability with dose response there.
I received an email newsletter from an herbalist I follow the other day, and straight out the gate she told her readers that Thanksgiving is a celebration of genocide. Bomb thrown, she went on to talk about how she could totally get behind a holiday that is about giving thanks. I don't disagree, but her approach was truly self-aggrandizing and alienating. Lots of that on display this time of year, IMHO.
All of this is to say that your writing is truly a breath of fresh air, Mark. You manage to address the uncomfortable truths without anger and guilt tripping, and propose a refreshing new view without preachiness. That is a remarkable skill! Thank you.
I am always confused by such assertions that anything we do *is* something in particular, as if some sort of natural law of gravity or justice applies to the social construction of reality and meaning. As I see it, the cycle of seasons and holidays is a cultural scaffolding on which we can construct our own stories and our own layers of meaning. Peel back the shallow commercial veneer and historical baggage and our holidays are longstanding traditions of gift giving/sacred birth, love, springtime renewal/resurrection, sacrifice for a higher cause, self-governance/self-determination, respect for hard work, honoring death and ancestors, and giving thanks.
Strip away the colonial story from Columbus Day and there isn't much left to celebrate, but Thanksgiving has never - for most of us at least - had much to do with its supposed origin story. Stripping away or replacing that story leaves the significance of the holiday unchanged or perhaps even enhanced.
Agreed 100%! As fate would have it, I am descended from both pilgrims and puritans, heroes and villains, many scoundrels, and at least one colonial-era Narragansett woman who decided that marrying a settler was her best option. Life is complicated. We do our best. And as you so eloquently say, observing the seasons and the blessings they offer will ground us, if we let them.
Thank you for sharing that wonderful, mighty prayer of gratitude. We so often exchange the wonder and gratitude of life for knowledge. You have inspired me to think of all that I am grateful for this Thanksgiving as I drive many hours to join with family for the holiday feast.
Mark, are you the immune tolerance guy?
I wouldn't say I'm *the* "immune tolerance guy", but I am the guy who wrote this:
https://ecosophia.dreamwidth.org/146211.html?thread=18362915#cmt18362915
Brian Mowrey has more or less convinced me that my original idea that tolerance is protective against severe infection/cytokine storms is probably wrong, and I must credit my original investigation of the idea to a twitter post by Robert Malone, but overall the hypothesis seems to be holding up. I'm frankly surprised that the idea that sneaking genetic code into otherwise healthy cells, thus causing them to make a foreign protein and get attacked in the absence of any other markers of infection, would likely lead to tolerance did not occur to a wider group of people earlier on.
An mRNA vaccine has even been specifically developed to *induce* tolerance, and the differences in inflammatory vs. non-inflammatory lipid packaging that supposedly make all the difference are far from convincing to me: https://www.nature.com/articles/s41587-021-00880-0
Thank you for responding.
I found your September post last June and wrote about it:
https://igorchudov.substack.com/p/vaccine-induced-tolerance-to-spike
It is possible that you did not get some MINOR details right, but you got the MAJOR ideas right. (who is always right about everything predicting the future? Not me either) I mentioned that June post of mine, referring to you, a few times recently so that your idea would get credit.
I find this topic of immune tolerance to be fascinating. Glad we crossed our paths.
Thanks for connecting. I've mostly kept a lower profile in this discussion and have mainly participated in Ecosophia discussions.
I'll be sharing this on the Ecosophia forum later today:
--------------------------
Some thoughts on IgG4 tolerance
Since tolerance has been much in the news recently, and since I originally introduced the concept here back in Open Post #5 (https://ecosophia.dreamwidth.org/146211.html?thread=18362915#cmt18362915), I thought I would offer some current thoughts and perspectives.
1. It’s a good study, but still only one (https://www.science.org/doi/10.1126/sciimmunol.ade2798). They validated their findings using quite a few different approaches. I do not doubt their findings with regard to a dramatic increase in anti-inflammatory IgG4 spike antibodies after multiple mRNA vaccinations, but it would be helpful to see it replicated.
2. The link between IgG4 tolerance and negative vaccine efficacy remains to be proven. We don’t yet have a direct correlation between IgG4 antibody levels and risk or severity of infection.
3. There are other potential explanations for negative vaccine efficacy. Among these are a) Antibody-Dependent Enhancement of Infection (ADEI), wherein the antibody response facilitates rather than inhibits infection, b) a broader-scale immune reprogramming/depletion induced by vaccination (e.g. https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v1), or c) a simple game of catch-up, given that the most-vaccinated people are still the least likely to have been infected to date (whether due to early vaccine efficacy or simply to being the most careful to avoid situations where viral spread is likely) (https://unglossed.substack.com/p/of-course-the-uber-boosted-are-the).
4. Despite these caveats, I think that tolerance is real and is contributing to the current high level of covid infections and excess deaths.
5. We should collectively have anticipated tolerance as a likely risk of repeated genetic vaccination. As Brian Mowrey writes: “…using host cells to produce a foreign antigen, absent associated molecular markers of viral infection, intrinsically risks tolerance: The immune system must associate spike protein with “self.”” (https://unglossed.substack.com/p/tolerance-maims-and-kills-potential) Developers of mRNA vaccines are not oblivious to this; they have even successfully developed a *tolerance-inducing* mRNA vaccine in mice: https://www.nature.com/articles/s41587-021-00880-0
6. Tolerance is probably mostly an mRNA thing. It is almost certainly going to be specific to *genetic* vaccinations, in which the body attacks its own cells serving as antigen factories rather than some injected particles carrying the antigens. The authors of the study found almost no IgG4 antibodies in people who had received a lifetime of tetanus vaccinations. It also appears to be substantially lower with the viral vector genetic vaccines, at least according to the one study published so far. This may be related to a lower spike dose and shorter duration of spike exposure, which correlates with a lower rate of post-vaccination fever and illness. The viral vector vaccines also generate antibodies against the vector itself, which makes boosters less likely to make it past the body’s defenses to generate spike protein.
7. Tolerance requires multiple exposures. It is unlikely to develop after a single shot; in fact, the second shot typically elicits a more severe reaction since the immune system was primed (rendered *less* tolerant) by the first one.
8. Tolerance is the inverse of reactivity. People who experienced a significant acute reaction to their second shot (high fever, body aches, etc.) but a more subdued reaction to their third and later shots are most likely developing some degree of spike tolerance.
9. Reactivity can probably induce tolerance. Given that there are no actual viruses or other signatures of infection present, it is likely that the “intelligence arm” of the immune system perceives the reactive, inflammatory response to the second dose as a mistake – along the lines of an overreaction to a bee sting. This will tend to lead to development of tolerance over time, particularly with additional exposures. Thus the fact that the mRNA shots make most people sicker than any other vaccination in common use is likely related to their propensity to induce tolerance.
10. There will likely be a wide range of individual variability in tolerance, despite identical exposures. This is true in the allergy world, e.g. with bee stings and responses to allergy shots. Individual immune responses vary widely, especially when it comes to tolerance vs. reactivity to a particular antigen following a particular pattern of exposure.
11. IgG4 tolerance is not “VAIDS” or broader-scale immunodeficiency. I don’t like “VAIDS” as a term. AIDS is a specific condition caused by progressive infection and destruction of CD4+ T-cells by HIV. Whatever might be occurring with immunodeficiency in the current context, it isn’t that, and so the effects will be different. I also don’t agree with Rintrah’s reasoning that tolerance to covid spike will equate to tolerance to flu and other viruses because viruses share functional parts (https://www.rintrah.nl/the-trainwreck-of-all-trainwrecks-billions-of-people-stuck-with-a-broken-immune-response/). Antibodies are sufficiently *specific* in their binding (even losing binding ability with mutations in the same virus), and respiratory viruses are sufficiently different, that this should not be a thing.
12. If covid infection leads to general immunodeficiency, then IgG4 tolerance may cause general immunodeficiency *indirectly*. This could occur due to frequent or chronic infection with SARS-CoV2 as a result of spike tolerance, assuming that infection is at least temporarily immunosuppressive as has been suggested and as is true also with measles.
13. mRNA vaccination may also directly cause general immunodeficiency or a reprogramming of immune response leading to a weaker response toward some targets like fungi or cancer cells. There are some hints in this direction, and it is reasonable to hypothesize that the immune system might respond to the self-attack induced by mRNA vaccination by broadly suppressing activity. This would however be a different mechanism than IgG4 tolerance and remains to be thoroughly investigated. It is even possible that the development of *specific* IgG4 tolerance over time might allow the immune system to relax its more *general* immunosuppressive tolerance in the context of continuing mRNA vaccination.
14. The negative effects of spike tolerance are likely to be mediated through failure to resist infection, toxicity of cumulative spike exposure, and direct viral tissue damage due to higher viral loads and longer duration of infection. If specific IgG4 tolerance is taking effect in the multiply-boosted, we would expect to see people getting infected with SARS-CoV2 more often, suffering more severe infections, taking longer to clear the virus, and suffering more cardiac complications linked to spike exposure. As noted above, though, tolerance is not the *only* hypothesis that could explain these things.
15. I would expect tolerance to be much more of a concern in the boosted (and especially the multiply-boosted) than in people who just received an original mRNA vaccination series. This is borne out to a limited extent by the fact that breakthrough infection substantially amplified IgG4 antibodies in the boosted but much less so in people who had only received the initial series (Fig. S8 of the linked study).
I agree on all these points except 1) I'm leaning back toward skepticism that AIDS is a sui generis viral etiology (ie the HIV > AIDS theory being valid), so I don't think the bar is necessarily very high for "VAIDS" to be a valid term. 2) I think the tetanus results confirmed IgG4 from repeat toxoid injection, there's just high variability with dose response there.
also let me now when you make your post and where to find it, I will save it in case I would mention it later.
I had to wait for the new weekly discussion to launch. It's up now at:
https://ecosophia.dreamwidth.org/215249.html?thread=38095825#cmt38095825
got it
Great ideas. I really like them.
I received an email newsletter from an herbalist I follow the other day, and straight out the gate she told her readers that Thanksgiving is a celebration of genocide. Bomb thrown, she went on to talk about how she could totally get behind a holiday that is about giving thanks. I don't disagree, but her approach was truly self-aggrandizing and alienating. Lots of that on display this time of year, IMHO.
All of this is to say that your writing is truly a breath of fresh air, Mark. You manage to address the uncomfortable truths without anger and guilt tripping, and propose a refreshing new view without preachiness. That is a remarkable skill! Thank you.
Thanks Valerie!
I am always confused by such assertions that anything we do *is* something in particular, as if some sort of natural law of gravity or justice applies to the social construction of reality and meaning. As I see it, the cycle of seasons and holidays is a cultural scaffolding on which we can construct our own stories and our own layers of meaning. Peel back the shallow commercial veneer and historical baggage and our holidays are longstanding traditions of gift giving/sacred birth, love, springtime renewal/resurrection, sacrifice for a higher cause, self-governance/self-determination, respect for hard work, honoring death and ancestors, and giving thanks.
Strip away the colonial story from Columbus Day and there isn't much left to celebrate, but Thanksgiving has never - for most of us at least - had much to do with its supposed origin story. Stripping away or replacing that story leaves the significance of the holiday unchanged or perhaps even enhanced.
Agreed 100%! As fate would have it, I am descended from both pilgrims and puritans, heroes and villains, many scoundrels, and at least one colonial-era Narragansett woman who decided that marrying a settler was her best option. Life is complicated. We do our best. And as you so eloquently say, observing the seasons and the blessings they offer will ground us, if we let them.
Moved to tears again….I’m grateful for you!💞
I'm grateful for you too!
A beautiful sense of awareness and gratitude, beautifully delivered. Thanks for these, and everything you are.
Thanks, brother!
Thank you for sharing that wonderful, mighty prayer of gratitude. We so often exchange the wonder and gratitude of life for knowledge. You have inspired me to think of all that I am grateful for this Thanksgiving as I drive many hours to join with family for the holiday feast.
I am grateful that my soul has this wet blue rock in the vast, mostly-empty, universe upon which to reside.