There might be a caveat with the second part of the conclusion. People who were not vaccinated (60 plus) or who only had two shots may have been those less likely to exhibit immunosenescence than those who did follow the vaccination to 3 shots. If this is the case, one might argue that the increased all-cause mortality risk due to 3rd shot vaccination merely pertains to levels of immunosenescence being higher in the 3rd shot vaccinated when compared with the unvaccinated. In other words the 3rd shot does not per se increase risk but reduces ADE risks.
The main reasons for the general lack of selection of immune escape variants prior to the vaccine roll-out in late December 2020 was because during natural infection, for the most part the innate immune system was able to clear or inactivate replication competent SARS-CoV-2 from the URT before the onset of the spike anti-IgG [Wolfel R et al., Nature, May 2020]. Perhaps more importantly, a growing body of evidence implies for natural infection unless the case of COVID-19 was severe/critical, there were few IgG1 or IgG3 antibodies to spike RBD in the nasal secretions and none in the saliva [Guerrieri M et al., Vaccines Basel, Dec 2021; Aksyuk AA Et al, Cell Rep Med Dec 2022]. However, with the second dose of COVID-19 vaccines (mRNA or virus vectored), these dangerous IgG antibodies to spike protein were commonly detected at high levels in the URT. It seems then the conversion only occurs systemically and not the URT since the omicron variants are much more transmissible???
Dr. Laderoute: There is an error in the charts you are showing. For all months, Covid-19 mortality plus non-C19 mortality should equal All-Cause mortality. For the March of 2021 line for Unvax, it does not add up. It looks like the Covid-19 mortality rate should be 3307.8 - 2716 = 591.8 (not 5919). The ratio of vax/unvax for the middle table, March 2021, would then be 283.9/591.8 = 0.48 (not 0.05).
The IgG4 response following a third mRNAvaccine-product dose doesnot change the higher all-cause mortalityrate fromreceiving these products.Loss of cancer-suppression may be important there.
Having less ADE, and possibly less rejection-reaction with IgG4 predominance would mitigating those scenarios somewhat.
Walter M.Chesnut:
An Urgent Warning: The Spike Protein Expressed On The Cell Surface Causes “Transplant Rejection” Of The Entire Body - Long COVID ,
Every Organ Expressing Spike Is Attacked As If It Were Transplanted Due To The Expression Of A Foreign Non-Self Protein On Cell Surfaces
Part II: In the Uversky et al, 2023 article essentially, they are arguing IgG4 is pathogenic. It is known that the anti-PD-1 antibodies used as immune checkpoint inhibitors (ICI) are IgG4 and their use can be associated with acute myocarditis (probably related to the specificity of the antibody moreso than the isotype). But Rubio-Infante N et al, European Journal of Heart Failure (July 2021) indicated 1.3% of people on ICI therapy experience cardiovascular adverse events (about 50% myocarditis). However, Salvo F et al, (Therapies March 7 2023) has shown the risk of myocarditis is higher in the Moderna over the Pfizer.BioNTech mRNA vaccine especially after the 2nd injection in males but under the age of 30. These demographics do not fit with the notion that the conversion of spike-specific IgG1/3 to IgG4 may be harmful to older people with comorbidities and not to young or healthy people. In another report by Keshavarz P et al, Tomography August 2022, only 1% of the males with myocarditis were in the age 60+ while 9% of the females with myocarditis were in the age group 60+. Interestingly the incidence of myocarditis was associated with the second dose (62.6 %), not so much the first dose (11.6 %) and HARDLY AT ALL, the booster dose (1.4%). The latter seems to argue that the third dose may alleviate the risk of myocarditis in contrast to the hypotheses of Uversky et al where they suggest harm (autoimmune myocarditis).
Thank you for the thoughtful, substantiated and fully-considered response to the assertion that "there might be a silver-lining to IgG4 desensitizing the immune system during chronic vaccine-induced exposure to spike-protein".
It's a bit of a stretch for the jabbed, seeking comfort in "it's not ALL bad" thoughts.
I and many others, are pleased to remain in the "control group".
Part I: I do get what you are saying that the conversion of spike specific IgG1/3 to IgG4 means in the host there is less rejection of autologous tissue that unfortunately expressed the spike protein due to the mRNA and/or adenovirus vaccines (iatrogenic autoimmunity) and thus provides a lower risk of dying. However, under the age of 60, this conversion appears to be generally as good as not being vaccinated (sometimes better perhaps related to adaptive T cell immunity or that the 3rd dose also induced some short lived innate immunity). On the other hand, for the 60+ while the mortality rates after the 3rd dose have definitely dropped when compared with the one and two doses, the mortality rates have not gone back to the unvaccinated levels. Is this because the IgG4 anti-spike antibodies are now magically pathogenic only in the 60+, or is it because in the absence of ADE, the higher risk of older people with comorbidities (i.e., those with immunosenescence of macrophages) can now be recognized. Because the autoantigens recognized by the IgG4 have not been clearly identified in IgG4 -related disease (IgG4-RD diagnosis is based on increased serum levels of IgG4) [Trampert DC et al, 2018] it is hard to envision how general elevations in the blood mediate specific disease, at this time.
Since it has been said that those who were infected with COVID-19 before the vaccine might not convert to spike specific IgG4 after vaccination, I wonder if a second infection such as by omicron variants remedies this? Do you think we need to test people for levels of spike specific IgG1/3 versus IgG4 or is it likely everyone is IgG4???
There might be a caveat with the second part of the conclusion. People who were not vaccinated (60 plus) or who only had two shots may have been those less likely to exhibit immunosenescence than those who did follow the vaccination to 3 shots. If this is the case, one might argue that the increased all-cause mortality risk due to 3rd shot vaccination merely pertains to levels of immunosenescence being higher in the 3rd shot vaccinated when compared with the unvaccinated. In other words the 3rd shot does not per se increase risk but reduces ADE risks.
The main reasons for the general lack of selection of immune escape variants prior to the vaccine roll-out in late December 2020 was because during natural infection, for the most part the innate immune system was able to clear or inactivate replication competent SARS-CoV-2 from the URT before the onset of the spike anti-IgG [Wolfel R et al., Nature, May 2020]. Perhaps more importantly, a growing body of evidence implies for natural infection unless the case of COVID-19 was severe/critical, there were few IgG1 or IgG3 antibodies to spike RBD in the nasal secretions and none in the saliva [Guerrieri M et al., Vaccines Basel, Dec 2021; Aksyuk AA Et al, Cell Rep Med Dec 2022]. However, with the second dose of COVID-19 vaccines (mRNA or virus vectored), these dangerous IgG antibodies to spike protein were commonly detected at high levels in the URT. It seems then the conversion only occurs systemically and not the URT since the omicron variants are much more transmissible???
Dr. Laderoute: There is an error in the charts you are showing. For all months, Covid-19 mortality plus non-C19 mortality should equal All-Cause mortality. For the March of 2021 line for Unvax, it does not add up. It looks like the Covid-19 mortality rate should be 3307.8 - 2716 = 591.8 (not 5919). The ratio of vax/unvax for the middle table, March 2021, would then be 283.9/591.8 = 0.48 (not 0.05).
Thank You, again,Dr. Laderoute.
The IgG4 response following a third mRNAvaccine-product dose doesnot change the higher all-cause mortalityrate fromreceiving these products.Loss of cancer-suppression may be important there.
Having less ADE, and possibly less rejection-reaction with IgG4 predominance would mitigating those scenarios somewhat.
Walter M.Chesnut:
An Urgent Warning: The Spike Protein Expressed On The Cell Surface Causes “Transplant Rejection” Of The Entire Body - Long COVID ,
Every Organ Expressing Spike Is Attacked As If It Were Transplanted Due To The Expression Of A Foreign Non-Self Protein On Cell Surfaces
https://wmcresearch.substack.com/p/an-urgent-warning-the-spike-protein
Part II: In the Uversky et al, 2023 article essentially, they are arguing IgG4 is pathogenic. It is known that the anti-PD-1 antibodies used as immune checkpoint inhibitors (ICI) are IgG4 and their use can be associated with acute myocarditis (probably related to the specificity of the antibody moreso than the isotype). But Rubio-Infante N et al, European Journal of Heart Failure (July 2021) indicated 1.3% of people on ICI therapy experience cardiovascular adverse events (about 50% myocarditis). However, Salvo F et al, (Therapies March 7 2023) has shown the risk of myocarditis is higher in the Moderna over the Pfizer.BioNTech mRNA vaccine especially after the 2nd injection in males but under the age of 30. These demographics do not fit with the notion that the conversion of spike-specific IgG1/3 to IgG4 may be harmful to older people with comorbidities and not to young or healthy people. In another report by Keshavarz P et al, Tomography August 2022, only 1% of the males with myocarditis were in the age 60+ while 9% of the females with myocarditis were in the age group 60+. Interestingly the incidence of myocarditis was associated with the second dose (62.6 %), not so much the first dose (11.6 %) and HARDLY AT ALL, the booster dose (1.4%). The latter seems to argue that the third dose may alleviate the risk of myocarditis in contrast to the hypotheses of Uversky et al where they suggest harm (autoimmune myocarditis).
Thank you for the thoughtful, substantiated and fully-considered response to the assertion that "there might be a silver-lining to IgG4 desensitizing the immune system during chronic vaccine-induced exposure to spike-protein".
It's a bit of a stretch for the jabbed, seeking comfort in "it's not ALL bad" thoughts.
I and many others, are pleased to remain in the "control group".
Part I: I do get what you are saying that the conversion of spike specific IgG1/3 to IgG4 means in the host there is less rejection of autologous tissue that unfortunately expressed the spike protein due to the mRNA and/or adenovirus vaccines (iatrogenic autoimmunity) and thus provides a lower risk of dying. However, under the age of 60, this conversion appears to be generally as good as not being vaccinated (sometimes better perhaps related to adaptive T cell immunity or that the 3rd dose also induced some short lived innate immunity). On the other hand, for the 60+ while the mortality rates after the 3rd dose have definitely dropped when compared with the one and two doses, the mortality rates have not gone back to the unvaccinated levels. Is this because the IgG4 anti-spike antibodies are now magically pathogenic only in the 60+, or is it because in the absence of ADE, the higher risk of older people with comorbidities (i.e., those with immunosenescence of macrophages) can now be recognized. Because the autoantigens recognized by the IgG4 have not been clearly identified in IgG4 -related disease (IgG4-RD diagnosis is based on increased serum levels of IgG4) [Trampert DC et al, 2018] it is hard to envision how general elevations in the blood mediate specific disease, at this time.
Great work, lovely to hear from someone who actually knows what they are talking about. The truth is the greatest antidote to propoganda.
Thank you so much!
Since it has been said that those who were infected with COVID-19 before the vaccine might not convert to spike specific IgG4 after vaccination, I wonder if a second infection such as by omicron variants remedies this? Do you think we need to test people for levels of spike specific IgG1/3 versus IgG4 or is it likely everyone is IgG4???