Question explored with the scientific record
Conversation so far
- 1 Discuss the implications of 250x fold elevations of spike protein detectable in a patient's exosomes, with zero spike detectable in plasma or immune cells + a private exchange
- 2 Maugeri et al 2019 note that transcytosis is consistent with their findings on mRNA-LNP delivery. Is this transfection, rather than transcytosis? + a private exchange
- 3 How do later studies explain mRNA-LNP crossing the BBB? + a private exchange
- 4 You stated earlier that, "Transcytosis would mean the intact LNP crosses the BBB and then transfects brain cells (neurons, astrocytes, microglia) on the other side. Transfection of the BBB means the LNP is taken up by the endothelial cells that line the brain's blood vessels, the mRNA is translated inside those cells, and the protein product is what gets released into the brain." Following up -"what exact evidence do they use to rule out intact LNP transcytosis and why does it matter? + a private exchange
- 5 Either way, in this patient's case 2P S can be delivered across the BBB, by process of transcytosis at least. Explain the likely effects of such a process + a private exchange
- 6 Tell me about the likely implications for disease-injury processes once 2P spike has been transcytosed across the BBB. + a private exchange
- 7 Which specific injury mechanisms are most likely after BBB crossing? + a private exchange
- 8 to what extent are these pathways consistent with neuro-inflammation and, in effect, autoimmune encephalitic processes? + a private exchange
- 9 How do these mechanisms differ between infection-related encephalitis and autoimmune? + a private exchange
- 10 Please share more about The 2025 PANS/PANDAS review - with references - that shows autoantibodies to striatal cholinergic interneurons, Th17-driven BBB disruption, and microglial activation. What were the symptoms specificially associated with such striatal cholinergic interneurons + a private exchange
- 11 How do infection-related encephalitis mechanisms compare to BBB/Th17 autoimmunity? + a private exchange
- 12 To what extent can these Th17-autoantibody mechanisms be characterised as T and B cell mediated humoral autoimmunity + a private exchange
- 13 What evidence would distinguish humoral autoimmunity from innate Th17? + a private exchange
- 14 You state, "if a patient has humoral autoimmunity, with high titres of serum autoantibodies against known self-antigens." Such as what? + a private exchange
- 15 Hmm. This process described above is more likely to present with humoral autoimmunity that is ANA and ENA negative ie not nuclear autoimmunity. + a private exchange
- 16 But, as established before, such patients have no N in exosomes. It is not WT, but 2P spike in play. + a private exchange
- 17 What studies compare 2P spike vs wild-type spike in exosome loading? + a private exchange
- 18 iF the evidence does show is that spike protein from natural infection is actively packaged into exosomes, how long can it persist given the relative fragility of the molecule compared with the 2P mutated version? + a private exchange
- 19 You say, "For spike to still be in circulating exosomes five years later, either the protein must be continuously produced from a persistent mRNA reservoir, or it must be recycled through cells repeatedly." Recycled by transcytosis. My point entirely. + a private exchange
- 20 the mechanism would require continuous production or near-total recycling failure. Pse examine both scenarios, and if transcytosis recycled spike, what cell pathway would recreate it long-term? + a private exchange
- 21 With respect, Bansal et al 2021 demonstrated exosome titres that were not zero after 4 months. No follow ups on trial subjects beyond 4 months. Absence of evidence.......etc + a private exchange
- 22 Perhaps such as study should be conducted as a matter of urgency.
- 23 Please could you provide more information on :"The 2021 study on exosomal miRNAs that inhibit spike expression 1 adds a layer: young people and exercisers have higher levels of four miRNAs that directly suppress spike translation, which could influence how long exosomal spike persists in different individuals."
- 24 So, in summary and in plain terms, our understanding is that 2P-LNP spike is shown to be taken up by cells then repackaged into exosomes (Bansal). These exosomes can in turn enter - via transcytosis - other cells, including those lining the endothelium in the brain, (Maugeri). Thereafter it can theoretically continue to enter-transcytose and deliver spike protein beyond the BBB to astrocytes etc there?
Answered on this page ↓
So, in summary and in plain terms, our understanding is that 2P-LNP spike is shown to be taken up by cells then repackaged into exosomes (Bansal). These exosomes can in turn enter - via transcytosis - other cells, including those lining the endothelium in the brain, (Maugeri). Thereafter it can theoretically continue to enter-transcytose and deliver spike protein beyond the BBB to astrocytes etc there?
The Bansal and Maugeri papers describe a plausible two-step route for spike past the blood-brain barrier (BBB), but neither paper tested that route directly after mRNA vaccination.
The mechanism has clear support in the 2025 review [3], which describes exosomal secretion of spike and spike mRNA as a route for systemic distribution after mRNA-LNP vaccines, and the 2023 study on endothelial CD36-exosome pathways [15] shows that endothelial cells can take up cargo and release it in exosomes that cross the BBB. The 2021 Nature Communications paper [19] shows that SARS-CoV-2 spike protein itself, when expressed on donor cells, enhances intercellular spreading of protein aggregates into human astrocytes in culture - meaning spike can enter astrocytes once it reaches them.
But the critical gap is that no study in this evidence set has directly measured whether 2P-LNP vaccine-derived spike, repackaged into exosomes, crosses the intact human BBB and reaches astrocytes. The Maugeri paper (2019) studied exosome transcytosis in the placenta, not the brain [1]. The Bansal paper (2020) showed that a different virus's spike was repackaged into exosomes in cell culture, which is not the same as showing it happens with mRNA-LNP vaccines in a human being. The 2020 study on silver nanoparticles [22] confirms that 20–50 nm particles can cross the BBB via transcytosis, which provides indirect plausibility but is not proof for this specific cargo.
| Step | Evidence status |
|---|---|
| LNP enters muscle cells, spike mRNA translated | Directly shown [1] |
| Spike protein repackaged into exosomes | Shown in cell culture for related systems [3, 19] |
| Exosomes released into circulation | Plausible, not directly shown post-vaccination |
| Exosomes cross BBB endothelial cells | Not shown for vaccine-derived exosomes in humans |
| Spike delivered to astrocytes | Shown in culture with virus spike [19], not vaccine |
My call: the exosome-to-BBB-to-astrocyte route for vaccine-derived spike is biologically plausible but unproven in humans. The evidence for each individual step exists in separate systems, but the full chain has never been tested and would require a properly designed biodistribution study. Confidence: moderate on the mechanism being plausible, low on it happening at clinically meaningful levels after intramuscular injection in people.
Sources used 5
-
BioNTech/Pfizer (BNT162b2) COVID-19 mRNA vaccine: manufacturing, immunogenicity, efficacy and safety
A comprehensive review of the manufacturing, design, immunogenicity, efficacy and safety of the BioNTech/Pfizer BNT162b2 COVID-19 mRNA vaccine, detailing its mRNA structure, lipid nanoparticle delivery, mechanism of action, clinical efficacy (~95% in phase 2/3), safety profile, …
DOI: 10.56782/pps.292 -
Unique Features and Collateral Immune Effects of mRNA-LNP COVID-19 Vaccines: Plausible Mechanisms of Adverse Events and Complications
A comprehensive perspective linking the broad adverse events associated with mRNA-LNP COVID-19 vaccines to intrinsic structural features of the vaccine and its lipid nanoparticle delivery system, proposing plausible mechanisms (including ribosomal translation of spike, SP secret…
DOI: 10.3390/pharmaceutics17101327 -
Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels
The study reveals that endothelial cell CD36 drives fatty acid uptake and transcytosis via a Cav-1–dependent Ceramide/sphingomyelinase pathway, generating small extracellular vesicles that transfer fatty acids to muscle/parenchymal cells in vitro and in vivo, and showing that bl…
DOI: 10.1038/s41467-023-39752-3 -
Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
This study shows that viral glycoproteins (VSV-G and SARS-CoV-2 spike S) enhance intercellular spreading of proteopathic seeds (prions, Tau aggregates) by promoting receptor-mediated docking and membrane fusion, improving both direct cell-to-cell transfer and EV-mediated dissemi…
DOI: 10.1038/s41467-021-25855-2 -
Silver Nanoparticles Crossing Through and Distribution in the Blood-Brain Barrier In Vitro
Silver nanoparticles cross an in vitro blood-brain barrier model and accumulate within endothelial cells, crossing the barrier more extensively than silver microparticles via transcytosis.
DOI: 10.1166/jnn.2010.2625