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The mRNA vaccines’ payload is ferried into human cells via complex lipid nanoparticles (LNPs) with a lipophilic formulation capable of traversing phospholipid bilayers, through endocytosis and other mechanisms. While some LNPs have been engineered with specific tropisms for target tissues, others have less selective tropisms (or are even potentially omnitropic), capable of entering diverse cell types. If the LNPs in COVID vaccines have a broad cell tropism, then they would be capable of entering and expressing the SARS-CoV-2 viral spike protein within the parenchyma of vital organs and tissues, well beyond the tropism of wild-type coronavirus. The resulting non-self protein, presented to immune surveillance via MHC-I complexes, would trigger a cytotoxic (CD8-mediated) immune response to the expressing cells, which could with time engender clinically significant tissue damage.
LNP-containing mRNA vaccines enlist both MHC-II-mediated (through dendritic cells and other APCs) and cytotoxic MHC-I-mediated immunostimulation, but against a far broader array of MHC-I-presenting cells and tissues than the wild-type virus, particularly for LNPs with unselective tissue tropisms. There is potential for enhanced immunostimulatory impact through this process, but also elevated risk of cytotoxic, inflammatory, and autoimmune effects, even more so if the liposomal particles can traverse the blood-brain barrier (which the COVID 19 mRNA vaccines do) to enter, for example, motor neurons or oligodendrocytes (the glial cells targeted in multiple sclerosis). Immune responses appear to be incremental and fleeting, both for natural and vaccine-mediated immunity, suggesting a likely need for multiple boosters after an initial inoculation. Therefore, if cytotoxic responses to integral tissues are transpiring through MHC-I-mediated presentation of SARS-CoV-2 spike protein, the effects may be at first subclinical, manifesting fully only after successive immunizations over months or years.
