Pathological Syncytia formation & PEG; Sfera et al. looks at this question: "Do Messenger RNA Vaccines Induce Pathological Syncytia?"; Syncytia correlated with severe disease; PEG was never used

by Paul Alexander

in an approved vaccine & its presence in Pfizer & Moderna therapeutics raised concerns, especially regarding anaphylactic and fusogenic adverse effects, promotes temporary permeabilization of Blood BB

This paper adds to the body of evidence surrounding the adverse effects we have seen and the grave harms post COVID gene injection vaccine administration (particularly Pfizer and Moderna mRNA injections).

SOURCE:

https://clinmedjournals.org/articles/ijpcr/international-journal-of-pathology-and-clinical-research-ijpcr-8-137.php?jid=ijpcr

PEG was added to the LNP to stabilize the mRNA and prolong its usability/action. PEG was ‘never used in an approved vaccine therefore, its presence in Pfizer-BioNTech and Moderna-1273 therapeutics raised concerns, especially regarding anaphylactic and fusogenic adverse effects [52,67,68]. Moreover, PEG promotes temporary permeabilization of the blood-brain barrier (BBB), a property exploited by the pharmaceutical industry for CNS delivery systems [69-71]. This may account, at least in part, for the rare VAERS-reported neuropsychiatric symptoms, including neurodegenerative disorders [72-74].

Furthermore, earlier studies have demonstrated that PEG may interfere with the conformational stability of proteins, indicating that syncytia, cellular senescence and, dysfunctional proteostasis are highly intertwined [75-77]. While the attention to PEG and the need to further study its relation to the potential vaccine adverse reactions is logical and appropriate, it must be noted that excipients other than PEG might be also be involved in such reported adverse reaction events [78].’

LNPs

‘Although transfection data is mostly proprietary, interrogation of LNP components can provide clues about the mRNA ingress into human cells [6]. For example, LNPs contain ionizable lipids, phospholipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and cholesterol that can attract host phagocytes to internalize the particle [48-50]. Both ionizable lipids and DSPC resemble PS, communicating to phagocytes readiness for engulfment [8]. Aside from comprising an established "eat me" signal, ePS can also convey "fuse me" cues to host phagocytes that can contribute to the unintended consequence of pathological syncytia formation [10]. The LNP component, cholesterol, is also a promoter of pathological cell-cell fusion as it can alter the asymmetry of cell membranes [50]. Moreover, as cell-cell fusion leads to premature cellular senescence and iatrogenic immunosuppression, it may partly explain the immune dysfunction documented in some vaccinated individuals [51-53].’

Polyethylene glycol (PEG)

‘PEG was added to the LNP to stabilize and prolong the mRNA duration of action (Figure 1). The extensive utilization of PEG over the past few decades, suggests that preexisting antibodies could trigger hypersensitivity to vaccines containing this molecule [54,55]. Aside from allergy, PEG is also an established chemical fusogen that can generate pathology by promoting polynucleation, aneuploidy, and genomic instability [56-59]. In addition, PEG up regulates intracellular Ca2+, activating the transmembrane protein 16F (TMEM16F), a lipid scramblase that flips PS on the cell surface, triggering fusion, premature cellular senescence, and immunosuppression [60-63]. As these phenotypes are virus-friendly, PEG-induced cell-cell fusion may inadvertently facilitate not only SARS-CoV-2 but also other viral infections [60,64-66]. Furthermore, ePS-activated ADAM 10 and 17 promote syncytia formation via metalloprotease pathway [40,42,43].’

DSPC and ionizable lipids

To deliver the liposome cargo to human immune cells, mRNA therapeutics must trick host phagocytes into internalizing LNPs by phagocytosis [79,80]. This is accomplished by decorating the liposomal particles with ionizable lipids and DSPC, an anionic phospholipid that mimics ePS and conveys readiness for phagocytosis [81,82]. This "eat me" signal is exploited by many viruses, including SARS-CoV-2, to enter host immune cells by engulfment [8].

Pfizer and Moderna vaccines were designed to "imitate" dying cells or apoptotic bodies by utilizing ionizable lipids and DSPC delivering mRNA directly to the immune cells' translation machinery [5]. However, DSPC's resemblance to PS may inadvertently activate ADAM 10 and 17, promoting pathological cell-cell fusion and subsequent pathology [40].

Taken together, LNPs mimicking ePS are engulfed by host immune cells, and generate anti-S antibodies by delivering the mRNA cargo to host ribosomes. However, in some cases the disruption of plasma cell asymmetry may inadvertently engender iatrogenic syncytia by activating the metalloprotease pathway.

Figure 1 below: N1-methylpseudouridine (m1Ψ)-modified mRNA (in the rectangle) is surrounded by a lipid nanoparticle (LNP) comprised of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and an ionizable lipid. Polyethylene glycol (PEG) is conjugated with the lipid molecules to increase the mRNA duration of action. The mRNA encodes for the full-length S antigen and is flanked by two untranslated regions (UTRs) and a polyadenylated (polyA) tail at the 3' end for stabilization. A cap at the 5' end offers further protection from exonuclease recognition.’