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.
Answered on this page ↓
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.
The short version: transcytosis recycling could explain persistent spike in exosomes, but the evidence here does not test it and the 250-fold elevation you describe is far beyond what any published mechanism accounts for.
The evidence you gave me contains no study that measured spike in exosomes years after vaccination, let alone at 250-fold elevation. The closest is a 2025 review that lists exosomal spread of spike as a plausible mechanism [11], but that is a theoretical proposal, not a measurement. The 2019 study on tumor-derived extracellular vesicles crossing the blood-brain barrier via transcytosis [9] shows that exosomes can be recycled through endothelial cells, but that is cancer biology, not vaccine-derived spike persistence. The 2025 microfluidic BBB model [8] confirms that extracellular vesicles can cross the barrier intact, but again, this is about transport, not about a protein being recycled for years.
Your transcytosis hypothesis has a fundamental problem. Exosomes are not stable structures. They are continuously produced and cleared, with a half-life measured in hours, not years. For spike to remain in circulating exosomes at high levels for five years, the protein must be continuously loaded into newly formed exosomes. That requires either a persistent source of spike production (which the evidence does not document for mRNA vaccines) or a recycling loop that returns spike to the exosome pathway after it has been taken up by cells. The 2019 study [9] shows that exosomes can be taken up by endothelial cells and re-released, but that is a single passage, not a five-year cycle.
The 250-fold elevation you mention is the real puzzle. Even if transcytosis recycles some spike, the concentration should decay over time as the protein is degraded. A sustained 250-fold elevation implies either ongoing production or a complete block on clearance. The evidence here has no data on either. The 2024 review [10] discusses self-DNA-driven inflammation after mRNA vaccination, and the 2025 review [11] lists spike persistence in plasma of myocarditis patients, but neither measures exosome titers or provides a mechanism for five-year persistence.
My call: transcytosis recycling is a plausible mechanism for short-term spike persistence, but the evidence here does not support it as an explanation for 250-fold elevation five years out. Confidence: low, because the relevant study was never done and the mechanism would require continuous production or near-total recycling failure.
Sources used 4
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A physiological microfluidic blood-brain-barrier model for in vitro study of nanoparticle trafficking and accumulation
The study introduces a horizontally oriented, multicellular microfluidic blood-brain barrier (mBBB) model and uses it to compare the trafficking and accumulation of extracellular vesicles, liposomes, and nanoplastics, finding that EVs show the greatest BBB transport with transpo…
DOI: 10.1101/2025.08.28.672885 -
Tumor-Derived Extracellular Vesicles Breach the Intact Blood–Brain Barrier via Transcytosis
Breast cancer–derived extracellular vesicles cross the intact blood–brain barrier via transcytosis, hijacking brain endothelial recycling pathways by downregulating Rab7 to boost transport, revealing a mechanistic basis for BBB traversal and implications for EV-based brain drug …
DOI: 10.1021/acsnano.9b04397 -
Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies
This narrative review proposes that self-DNA-driven inflammation contributes to severe COVID-19 and some mRNA vaccine adverse events, drawing parallels with HIV-1, trauma, and autoimmune diseases.
DOI: 10.3389/fimmu.2023.1259879 -
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