Speed of science? A year and a half after Mark L posted his tolerance hypothesis on this forum, science seems to be catching up. This study has the telling title "IgG4 Antibodies Induced by mRNA Vaccines Generate Immune Tolerance to SARS-CoV-2’spike Protein by Suppressing the Immune System" (https://doi.org/10.20944/preprints202303.0441.v1)
It is a long piece and interesting to read (I haven't yet read it all though). Interesting is that it connects the IgG2 --> IgG4 replacement with several pathologies that we are all too familiar with. From the summary:
"In conclusion, the immune tolerance mechanism induced by mRNA vaccines could have at least 6 negative unintended consequences:
1) By ignoring the spike protein synthesized as a consequence of vaccination, the host immune system becomes vulnerable to re-infection with the new Omicron subvariants, allowing for free replication of the virus once a re-infection takes place. In this situation, we propose that even these less pathogenic Omicron subvariants could cause significant harm and even death in individuals with comorbidities and immuno-compromised.
2) mRNA and inactivated vaccines temporally impair interferon signaling [125,126], causing immune suppression and leaving the individual in a vulnerable situation against any other pathogen. In addition, this immune suppression could allow the re-activation of latent viral, bacterial, or fungal infections, and might also allow uncontrolled growth of cancer cells [127].
3) A tolerant immune system can allow SARS-CoV-2 persistence in the host and promote the establishment of a chronic infection, similarly to that generated by the hepatitis B virus (HBV), the human immune deficiency virus (HIV), and the hepatitis C virus (HCV) [128].
4) The combined immune suppression (produced by SARS-CoV-2 infection and further enhanced by vaccination) could explain a plethora of autoimmune conditions, cancers, re-infections, and deaths temporally associated with both. It is conceivable that the excess deaths reported in several highly COVID-19-vaccinated countries may be explained, in part, by this combined immunosuppressive effect.
5) Repeated vaccination could also lead to auto-immunity: In 2009, the results of an important study went largely unnoticed. Researchers discovered that in mice that are otherwise not susceptible to spontaneous autoimmune disorders, repeated administration of the antigen promotes systemic autoimmunity. The development of CD4+ T cells that can induce autoantibodies (autoantibody-inducing CD4+ T cells, or aiCD4+ T cells), which had their T cell receptors (TCR) modified, was triggered by excessive stimulation of CD4+ T cells. The aiCD4+ T cell was generated by new genetic TCR modification rather than a cross-reaction. The excessively stimulated CD8+ T cells induced them to develop into cytotoxic T lymphocytes (CTL) that are specific for an antigen. These CTLs were able to mature further by antigen cross-presentation, so in that situation, they induced autoimmune tissue damage resembling systemic lupus erythematosus (SLE) [129]. According to the self-organized criticality theory, when the immune system of the host is continually overstimulated by antigen exposure at concentrations that are higher (see page 11) than the immune system's self-organized criticality can tolerate, systemic autoimmunity inevitably occurs [130]. It has been proposed that the amount and duration of the spike protein produced are presumably affected by the higher mRNA concentrations in the mRNA-1273 vaccine (100 μg) compared to the BNT162b2 vaccine (30 μg) [94]. Thus, it is probable that the spike protein produced in response to mRNA vaccination is too high and last too much time in the body. That overwhelms the capacity of the immune system, thus leading to autoimmunity [129,130]. Indeed, several investigations have found that COVID-19 immunization is associated with the development of autoimmune responses [131-148].
6) Increased IgG4 levels induced by repeated vaccination can lead to autoimmune myocarditis: It has been discovered that IgG4 antibodies can also cause an autoimmune reaction by impeding the immune system`s ability to be suppressed by regulatory T cells [86]. Patients using immune checkpoint inhibitors alone or in combination have been linked to occurrences of acute myocarditis [87-90], sometimes with lethal consequences [91]. As anti-PD-1 antibodies are class IgG4, and these antibodies are also induced by repeated vaccination, it is plausible to suggest that excessive vaccination is associated with the occurrence of an increased number of myocarditis cases and sudden cardiac deaths. Finally, these negative outcomes are not expected to affect all people who have received these mRNA vaccines. Individuals with genetic susceptibility, immune deficiencies, and co-morbidities probably would be the most likely to be affected. However, this gives rise to a disturbing paradox: if people who are the most affected by the COVID-19 disease (the elderly, diabetics, hypertensive, and immunocompromised people like those with HIV) are also more susceptible to suffering the negative effects of mRNA vaccines, is it then justified to booster them? As Omicron subvariants have been demonstrated to be less pathogenic, and mRNA vaccines do not protect against re-infection, clinicians should be aware of the possible detrimental effects on the immune system by administering boosters."
I'm curious what others think of this. Can so many pathologies associated with the vaxx get pinned onto the IgG4 increase?
PS It might be worthwile to save a copy of the piece before it gets "retracted".
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branchandroot
Tolerance
Date: 2023-03-29 11:25 am (UTC)It is a long piece and interesting to read (I haven't yet read it all though). Interesting is that it connects the IgG2 --> IgG4 replacement with several pathologies that we are all too familiar with. From the summary:
"In conclusion, the immune tolerance mechanism induced by mRNA vaccines could
have at least 6 negative unintended consequences:
1) By ignoring the spike protein synthesized as a consequence of vaccination, the host
immune system becomes vulnerable to re-infection with the new Omicron subvariants,
allowing for free replication of the virus once a re-infection takes place. In this situation,
we propose that even these less pathogenic Omicron subvariants could cause significant
harm and even death in individuals with comorbidities and immuno-compromised.
2) mRNA and inactivated vaccines temporally impair interferon signaling [125,126],
causing immune suppression and leaving the individual in a vulnerable situation against
any other pathogen. In addition, this immune suppression could allow the re-activation
of latent viral, bacterial, or fungal infections, and might also allow uncontrolled growth of
cancer cells [127].
3) A tolerant immune system can allow SARS-CoV-2 persistence in the host and
promote the establishment of a chronic infection, similarly to that generated by the hepatitis
B virus (HBV), the human immune deficiency virus (HIV), and the hepatitis C virus
(HCV) [128].
4) The combined immune suppression (produced by SARS-CoV-2 infection and
further enhanced by vaccination) could explain a plethora of autoimmune conditions, cancers,
re-infections, and deaths temporally associated with both. It is conceivable that the
excess deaths reported in several highly COVID-19-vaccinated countries may be explained,
in part, by this combined immunosuppressive effect.
5) Repeated vaccination could also lead to auto-immunity: In 2009, the results of an
important study went largely unnoticed. Researchers discovered that in mice that are
otherwise not susceptible to spontaneous autoimmune disorders, repeated administration
of the antigen promotes systemic autoimmunity. The development
of CD4+ T cells that can induce autoantibodies (autoantibody-inducing CD4+ T
cells, or aiCD4+ T cells), which had their T cell receptors (TCR) modified, was
triggered by excessive stimulation of CD4+ T cells. The aiCD4+ T cell was generated
by new genetic TCR modification rather than a cross-reaction. The excessively
stimulated CD8+ T cells induced them to develop into cytotoxic T lymphocytes
(CTL) that are specific for an antigen. These CTLs were able to mature further
by antigen cross-presentation, so in that situation, they induced autoimmune
tissue damage resembling systemic lupus erythematosus (SLE) [129]. According to
the self-organized criticality theory, when the immune system of the host is continually
overstimulated by antigen exposure at concentrations that are higher (see page 11) than
the immune system's self-organized criticality can tolerate, systemic autoimmunity inevitably
occurs [130].
It has been proposed that the amount and duration of the spike protein produced are
presumably affected by the higher mRNA concentrations in the mRNA-1273 vaccine (100
μg) compared to the BNT162b2 vaccine (30 μg) [94]. Thus, it is probable that the spike
protein produced in response to mRNA vaccination is too high and last too much time in
the body. That overwhelms the capacity of the immune system, thus leading to autoimmunity
[129,130]. Indeed, several investigations have found that COVID-19 immunization
is associated with the development of autoimmune responses [131-148].
6) Increased IgG4 levels induced by repeated vaccination can lead to autoimmune
myocarditis: It has been discovered that IgG4 antibodies can also cause an autoimmune
reaction by impeding the immune system`s ability to be suppressed by regulatory T cells
[86]. Patients using immune checkpoint inhibitors alone or in combination have been
linked to occurrences of acute myocarditis [87-90], sometimes with lethal consequences
[91]. As anti-PD-1 antibodies are class IgG4, and these antibodies are also induced by repeated
vaccination, it is plausible to suggest that excessive vaccination is associated with
the occurrence of an increased number of myocarditis cases and sudden cardiac deaths.
Finally, these negative outcomes are not expected to affect all people who have received
these mRNA vaccines. Individuals with genetic susceptibility, immune deficiencies,
and co-morbidities probably would be the most likely to be affected. However, this
gives rise to a disturbing paradox: if people who are the most affected by the COVID-19
disease (the elderly, diabetics, hypertensive, and immunocompromised people like those
with HIV) are also more susceptible to suffering the negative effects of mRNA vaccines,
is it then justified to booster them? As Omicron subvariants have been demonstrated to
be less pathogenic, and mRNA vaccines do not protect against re-infection, clinicians
should be aware of the possible detrimental effects on the immune system by administering
boosters."
I'm curious what others think of this. Can so many pathologies associated with the vaxx get pinned onto the IgG4 increase?
PS It might be worthwile to save a copy of the piece before it gets "retracted".