(Decock et al., 2016). APP contains a total of four GxxxG motifs (one fewer than the spike protein).
A case study presented the case of a man who developed CKD simultaneously with symptomatic COVID-19. The authors proposed that infection with SARS-CoV-2 precipitates or accelerates neurodegenerative diseases [30]. A theoretical paper published by researchers in India showed that the spike protein binds to a number of aggregation-prone prion-like proteins, including amyloid beta, α-synuclein, tau, PrP and TDP-43. They argued that this could initiate aggregation of these proteins in the brain, leading to neurodegeneration [31].
Tracing the Vaccine Trail to the Spleen
It is important to understand what happens to the contents of a vaccine after it is injected into the arm. Where does it travel in the body, and what does it do in the places where it settles in? Vaccine developers are keen to know whether the vaccine induces a strong immune response, reflected in high antibody production against the spike protein, in the case of COVID-19 vaccines. And to do this, they need to trace its movement in the body.
CD8+ T-cells are cytotoxic immune cells that can kill cells that are infected with a virus. They detect an immune complex with viral proteins that are exposed on the surface of an infected cell. A study on an adenovirus-vector based vaccination of mice used clever methods to produce a marker that could track the activity of CD8+ T-cells in the lymph system and the spleen, in the days following vaccination [32].
It can be inferred that immune cells (antigen-presenting cells, where the “antigen” is the spike protein) were initially present at the arm muscle injection site and synthesized the virus spike protein from the vaccine DNA code, exposing it on their surface. Once activated by the foreign protein, they translocated into the draining lymph nodes and finally made their way to the spleen via the lymph system. The CD8+ T-cells are idly waiting within the lymphatics until they spot an infected immune cell. Researchers could detect activation of CD8+ immune cells over time and inferred that this was caused by the arrival of the contents of the vaccine to the site where these immune cells reside. Activated CD8+ T-cells first appeared in the draining lymph nodes, but after five days began to show up in the spleen. Their numbers there peaked sharply by 12 days and then remained high with a slow decay up to 47 days, when the researchers stopped looking. What this means is that the vaccine is picked up by antigen-presenting cells at the injection site and carried to the spleen via the lymph system. The carrier cells then hang out in the spleen for a long time. And this is where the danger lies in terms of the potential to cause prion disease.
In the paper that Greg Nigh and I published recently on the mRNA vaccines, we argued that the mRNA vaccines are rather perfectly set up to produce a very dangerous situation in the spleen that is poised to launch a prion disease. Given the fact that the DNA vector vaccines also end up concentrated in the spleen, I think that the same thing holds true for them as well. The spleen is where the action is for seeding misfolded prion proteins. The vaccine-infected cells have been programmed to produce large amounts of spike proteins. Prion proteins misfold into damaging beta-sheet oligomers when there are too many of them in the cytoplasm. Might the spike protein do the same?
Three out of the four COVID-19 vaccines currently on the market in the U.S. and Europe (Pfizer, Moderna, and J&J) use a genetic code for the spike protein that has been slightly tweaked, in order to produce a more potent antibody response [33]. Normally, after binding to the ACE2 receptor, the spike protein spontaneously changes its shape in a dramatic way in order to fuse with the membrane of the cell. In a Web publication, Ryan Cross described this action very graphically based on a spring-like model, as follows: “When the spike protein binds to a human cell, that spring is released, and the two helices and the loop straighten into one long helix that harpoons the human cell and pulls the virus and human membranes close together until they fuse.” [33]. As Cross explains, through trial and error, but taking structural information into account, researchers came up with the idea of swapping out two adjacent amino acids for prolines in the membrane fusion domain in order to stabilize the shape of the spike protein in its pre-fusion form. In this form, it exposes critical antigenic areas, and this assures more rapid formation of matching antibodies, the only goal of the vaccine design. This also prevents the protein from fusing with the plasma membrane of a host cell. I’d imagine that the spike protein attaches to the ACE2 receptor and then gets stuck there, like a sitting duck. But a worrisome thought is whether this open state, not fused with the membrane, might more closely resemble the shape of a misfolded prion-like protein like amyloid beta than does the collapsed shape it needs to go into the membrane?
Tetz and Tetz have argued in a published online preprint that prion-like domains in the spike protein enable higher affinity for the ACE2 receptor, making the virus more virulent than its earlier cousins [34]. These same authors published an earlier peer-reviewed journal paper where they observed that many other viruses have proteins in their coat that have distinct features of prion proteins [35].