Related to someone's elses disbeliefs in how proteins produced from a mRNA vaccine end up in B cells; in theory the process could be more complicated than "naked" egress (which arguably does have simplicity in its favor). There's at least one paper that discussed spike proteins observed egressing in extracellular vesicles (following mRNA vaccination) but it doesn't really say whether this is the common route. And from the general gist of that paper, EVs seem to interfere with detection, so I'm guessing that's not the usual route. For yet another alternative, I could imagine that transfected cells first get killed by CD8 T cells and it's mostly this debris that gets picked up by B cells.

Interestingly, on the last angle, one review mentioned that

Comparative studies performed by our research group and others demonstrated that nucleoside-modified mRNA LNPs outperformed unmodified mRNA LNPs in translation capacity, but failed to elicit successful CTL [cytotoxic T cell] responses due to the drastically reduced production of type I IFNs [119, 157].

So it seems that the mRNA vaccines currently in clinical use for infectious diseases like Covid-19 (which do use nucleoside-modified mRNA) are pretty unsuccessful at killing cells, which makes the 3rd pathway I was considering above somewhat unlikely as a major contributor. (The research group which wrote that review seems focused on cancer immunotherapeutics, and the two cited studies definitely are about that. The lack of CTL activation is a big deal for cancer therapy.)

So, what direct evidence is there for how proteins most often come out cells following mRNA vaccination, particularly in nucleoside-modified vaccines?

  • $\begingroup$ During (mRNA) vaccination the spikes mostly don't exit the cells, they get anchored onto the surface membrane. It means that -something nobody talks about- they are likely taken by (dendritic) cells after the cell dies, because the cell is detected by the immune system as "infected". Klling (+phatocytize+presenting on MHC-II the non-self parts) the infected cells is something else almost nobody talks about, whereas it is a very important part of the immune system. $\endgroup$
    – reuns
    Oct 31, 2021 at 19:50
  • $\begingroup$ At the 2nd dose things are obvious: the spikes on the surface of the cell are detected by the antibodies produced after the 1st dose which triggers antibody-dependent cell cytotoxicity (NK,..) and phagocytosis (macrophage,dendritic cells,..) $\endgroup$
    – reuns
    Oct 31, 2021 at 19:58
  • 2
    $\begingroup$ This paper did a serious study of the trafficking of the spike, adding a "HA-tag" (in S1) to detect the spike with labeled antibodies. $\endgroup$
    – reuns
    Oct 31, 2021 at 20:39
  • $\begingroup$ @reuns: Thanks for the link. Somewhat inconclusive though. Regarding your other comments, I doubt cell death is the major pathway because the vaccine is administered IM and muscle cells don't regenerate if they completely die (they have complex repair procedures if they're only damaged), but there have been no reports of people losing deltoid muscle strength following vaccination. If killer T-cells persistently target muscle cells it results in major pathologies like IBM (Inclusion Body Myositis), which is very hard to treat. $\endgroup$ Oct 31, 2021 at 23:04
  • $\begingroup$ S.Seneff, G.Nigh suggested that B cells are activated in spleen, not in the muscle. "... the migration of immune cells carrying a cargo of mRNA nanoparticles via the lymph system into the spleen. These immune cells would produce spike protein... and the spike protein would induce B cell generation of IgG antibodies... neutrophils in the marginal zone of the spleen... interact with B cells, inducing antibody production (Puga et al., 2011). This is likely crucial for successful vaccination outcome." dpbh.nv.gov/uploadedFiles/dpbhnvgov/content/Boards/BOH/Meetings/… $\endgroup$ Nov 1, 2021 at 8:08


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