Further information

[wste...@williamstewart.com]

(Personal communication from Dr. Ulm, with his permission.)

The only other "live discussion" resource I can think of offhand is the Rapid Responses section to Peter Doshi's editorial at BMJ with questions on (primarily) the mRNA vaccines' efficacy and clinical measurement points -- that's actually where I posted some of my organized thoughts on this first, and hopefully there'll be some follow-up discussion there as well since Peter asked so many valuable pointed questions to kick off the discussion.
https://www.bmj.com/content/371/bmj.m4037/rapid-responses

Otherwise, the VAERS database itself can be useful to provide hints about potential issues with ADE or tissue mis-localization -- thankfully not a deluge of adverse events yet, though does appear higher than traditional vaccines -- albeit difficult to pin down pathophysiological fine points from the VAERS alone given the vast patient heterogeneity:    https://vaers.hhs.gov/

Further:

The SARS-CoV-2 spike protein wouldn't be stable for any extended period of time on the surface of oligodendrocytes or other glial cells in that worrisome scenario. Rather, if the proprietary lipid nanoparticles from Pfizer and Moderna are delivering the mRNA vaccine so as to translate the coronaviral spike protein in quantity, within oligodendrocytes (or CNS neurons even more concerningly), the expression would likely be transient -- at most weeks before mRNA degradation by ribonucleases -- but the concern is if this might still be sufficient to initiate the pathogenesis of a multiple sclerosis or even ALS-like phenotype, especially if boosters are involved. The model, in essence, is that neurons and glia (along with cells in other critical tissues, such as the kidneys or GI tract) would be turned into errant "antigen-presenting cells" by an mRNA vaccine with poorly controlled tissue localization, but since they'd be presenting the viral spike protein in complex with MHC Type I surface proteins (unlike the MHC Type II used by e.g. dendritic cells), they'd be targeted for destructive by cytotoxic CD8 lymphocytes, which makes sense immunologically. (Only phagocytosis, by e.g. macrophages or dendritic cells/Langerhans cells, engenders MHC-2 presentation, otherwise a cell presents the foreign protein in conjunction with MHC-I and so "looks infected," thereby becoming a target of killer T-cells.)  

As to the potential for serious disease to arise from this mechanism if indeed the mRNA vaccines are forcing glial cells and/or nerve cells to express the SARS-CoV-2 protein in conjunction with MHC-1, the reasoning is as follows. This potential is partly because the menagerie of cell types behind the blood-brain barrier often don't regenerate very well, especially the neurons but also many glial cells. This is one reason that MS and ALS often have a sort of indolent, intermittently progressive pathophysiology over years -- subclinical damage is occurring in the background, but takes years to "break the clinical threshold" and manifest to a physician. Another factor behind this is that waning immunity (after either immunization or COVID-19 infection) would likely mean repeat vaccinations and recurrent cycles of damage if the above process is indeed occurring. But it's also because the specifics of immunopathogenesis in many autoimmune disorders, especially for MS (ALS classically isn't autoimmune but auto-reactive T-cells would produce the same net effects), are rather mysterious, and we're not entirely sure why the T-cells are turned against self antigens. However, a common refrain we were taught in med school is that there's an initial cross-reaction involving a viral (or in this case, vaccinated) foreign protein in complex with MHC-I which leads to a transitory cytotoxic response against e.g. oligodendrocytes or other sensitive cells or tissues, but the cytotoxic T lymphocytes (which don't normally target cells like this) then persist in attacking the self cells even when the antigen itself is no longer present on the surface. As one med school professor explained it, "You absolutely DO NOT EVER WANT a cytotoxic process to be initiated against tissues in 'privileged corridors' such as behind the BBB, blood-follicle barrier (BFB) or blood-testis barrier (BTB) -- this is a formula for creating autoreactive cells to wreak havoc down the road.")

With the mRNA vaccines there is the potential that we'd be provoking a cytotoxic T lymphocyte response against a variety of sensitive tissues in those protected corridors, or others (like the kidney, heart, pancreas, thyroid, or adrenal glands) that really don't regenerate well. The critical distinguishing factor is that other vaccine modalities (like inactivated virus, protein subunit, or even live attenuated) simply don't do this at all -- their cellular tropism and tissue trafficking are highly constrained. (That's the basis for the "Type 1" and "Type 2" classifications for conventional vaccines I used in the contribution to the BMJ Rapid Response --  https://www.bmj.com/content/371/bmj.m4037/rapid-responses  )

Whereas the mRNA vaccines' lipid nanoparticles can have an extremely broad tropism, but because Pfizer and Moderna have declared their lipid nanoparticles to be trade secrets and, apparently, refused to allow them to be tested in e.g. animal studies to truly measure their tissue localization.  This is very unfortunate -- in gene therapy, we obsess about tissue localization, and any self-respecting IRB would have tossed a clinical trial proposal out the window if there was not a lot of solid tissue trafficking data, from multiple independent labs. It was just that important, and it was one of the centerpieces of the safety data needed to get even prelim approval for compassionate-use gene therapy for a rare disease, let alone a shot being used for mass vaccination of healthy people. And it's all because of the scenarios outlined above.

This is what makes this massive gap in the literature on the mRNA vaccines, and the relative hesitancy of the regulatory committees to demand such tissue localization data as the EU evaluation period proceeds on (or e.g. T1/T2-weighted MRI to assay for potential subclinical demyelination) so unusual, since Institutional Review Boards typically demand a vast array of such tissue localization data to even commence Phase I clinical trials.  

On the positive side, we can hope that there are serious papers in serious scientific journals waiting to be written on the mRNA vaccines' tissue localization (which, again, would require testing these specific proprietary nanoparticles used by Pfizer and Moderna, since the LNP recipes and formulations vary so widely in the literature).