Recently, I wrote about a new paper by Hickey et al. entitled ‘Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera’. There is more to add.
The study examined sera from individuals vaccinated with Moderna and Pfizer Covid vaccines. The authors reported that one month after the third Pfizer vaccine, three markers were upregulated:
- Upregulation of UB2D1/PolyUbiquitin K48
Involved in antiviral mechanisms and in protein degradation.
- Upregulation of CHAC1
Involved in glutathione depletion.
- Upregulation of Cancer/testis antigen 1
Involved in cancer detection.
The first two markers are involved in a process called the Unfolding Protein Response (UPR).
The UPR is a process that happens when a part of the cell called the endoplasmic reticulum, where proteins are folded, is under stress. If the normal process of folding proteins becomes overwhelmed or disturbed in any way, the UPR comes into action.
Downstream pathways of UPR are shown below (Figure 1).
Figure 1. Downstream pathways of Unfolded Protein Response.
The right pathway activates CHAC (that we now know is upregulated in Pfizer vaccinees) that depletes glutathione. That signals a problem in the cell, and the cell cycle is paused. If the problem (stress in the endoplasmic reticulum) is not resolved, the cell goes into the next phase: programmed cell death — either apoptosis or ferroptosis. What are the potential consequences of those actions? Kadowaki and Nishito answer that for us:
Dysfunction of the UPR, or prolonged ER stress, disrupts ER homeostasis. A large number of groups have described the relation between ER stress responses and a variety of human diseases, including neurodegenerative disease, metabolic disease, inflammatory disease, diabetes mellitus, cancer, and cardiovascular disease.
One of the main reasons for such serious pathologies is a lack of glutathione. Glutathione has a protective and pathogenic role. It is important in balancing oxidative stress, which protects us from neurodegenerative disease,cardiovascular disease, and cancer.
The left pathway activates PERK that can down regulate proteins. Liu et al. noted that during a heart attack (MI),PERK’s down regulating of ion channels may lead to sudden death. And Inhibiting PERK’s down regulation of ion channels may prevent sudden death.
In conclusion, we found that activated PERK during MI contributed to arrhythmia risk [and sudden death] by the downregulation of select cardiac ion channels. PERK inhibition prevented these changes and reduced arrhythmia risk.
What if the UPR was activated before a heart attack or another heart pathology? Would that increase the chances of sudden death?
But how is the cell’s endoplasmic reticulum being stressed?
Echavarria-Consuegra et al. tell us how:
Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR.
There, they are describing a natural infection, but the same logically holds true for Spike protein from a vaccine.Vaccinees’ UPR is probably caused by Spike protein in the endoplasmic reticulum one month after their vaccination.
Glutathione depletion is caused by the Unfolded Protein Response as a result of endoplasmic reticulum stress and is of concern. Cells depleted of glutathione may also present a problem for those being treated with certain drugs, e.g. a cancer medication called cyclophosphamide:
Administration of cyclophosphamide at a dose which is lethal to 10% of control athymic nude mice resulted in sudden death within 3 h in all mice that had been pretreated with the glutathione synthesis inhibitor.
The third marker raised in the paper by Hickey et al. was Cancer/testis antigen 1, which is normally used to detect cancer.
In conclusion, research has demonstrated raised markers in Covid vaccinees; one was a cancer marker, and the others were involved in the UPR. I have described some of the mechanisms and pathologies involved in the UPR. The activation of the UPR is most likely due to vaccine Spike protein in the endoplasmic reticulum. Potential pathologies resulting from the UPR, including neurodegenerative disease, cancer, and cardiovascular disease have been discussed, as well as the potential for sudden death.
It shouldn’t be lost on the reader that the pathologies described above somewhat comport with those now associated with the Covid vaccines. Viruses, like those leading to Covid and the flu, for example, are known to use the endoplasmic reticulum and induce the UPR, but in nature we have balance, so that response is usually short-lived. But if modern vaccines utilising mRNA technology continue to produce viral proteins chronically in the endoplasmic reticulum inducing the UPR, with all the attendant risks, then the resultant uptick in serious and even fatal pathologies may be unprecedented.
NB Moderna had mixed results depending on sex: Males had Upregulation of UB2D1/PolyUbiquitin K48; females had Upregulation of UB2D1/PolyUbiquitin K48; and CHAC1.
