When mRNA (from a vaccine) enters a cell and the transcription process gets underway, the host cell effectively becomes an antigen factory. How does the antigen leave the cell so that it can trigger the intended immune response, and what is the fate of the host cell? As I understand it, one mRNA molecule can produce many antigen particles before it decays; does this continue until the host cell ruptures? After antigen production has shut down, does the host cell "get back to its normal life"?
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The Covid-19 virus (like all enveloped [corona]viruses) does not exit the cell through lysis. So it's doubtful the protein itself does that.– got trolled too much this weekCommented May 18, 2021 at 12:49
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1Isn't the cell killed by the immune system when it starts presenting spike protein on its surface?– endolithCommented May 19, 2021 at 20:42
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1There's actually a very old article (from 2003) that discussed the issue of whether it's desirable or not that such vaccines induce cell death jci.org/articles/view/19069 But I can't find something more recent.– got trolled too much this weekCommented May 20, 2021 at 6:06
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1That old article noted that "Considering studies that demonstrate that the induction of apoptosis enhances immune responses induced by a DNA vaccine, it is quite surprising that the reverse strategy, i.e., a reduction of in vivo apoptosis, was found to strongly enhance the immunogenicity of a DNA vaccine." So I'm guessing the emphasis shifted to not causing cell death with such vaccines thereafter.– got trolled too much this weekCommented May 20, 2021 at 6:13
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Re "...quite surprising that the reverse strategy, i.e., a reduction of in vivo apoptosis, was found to strongly enhance the immunogenicity..." My idea is that there is "pyrolysis" in contrast to apoptosis as an inflammatory, less regulated way of cell death that leaves a whole lot of cell debris which especially B cells I propose are eager to take up.– Peter BernhardCommented Mar 25, 2022 at 13:01
1 Answer
I'm not a biologist, and it's difficult to find a straightforward explanation, but it sounds like the cells present the spike protein on their surface, and are then recognized as infected and killed by T-cells.
Some of the spike proteins form spikes that migrate to the surface of the cell and stick out their tips. The vaccinated cells also break up some of the proteins into fragments, which they present on their surface. These protruding spikes and spike protein fragments can then be recognized by the immune system
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The antigen-presenting cells can also activate another type of immune cell called a killer T cell to seek out and destroy any coronavirus-infected cells that display the spike protein fragments on their surfaces.
https://www.nytimes.com/interactive/2020/health/moderna-covid-19-vaccine.html
In an article about N protein vaccines:
Tiny fragments of N protein are then displayed on the surface of infected cells. T cells recognise these fragments, identify cells as infected, then kill the cell and consequently any virus.
Presumably vaccinated cells present the spike protein on the surface the same way as infected cells, and are killed in the same way, but neither of these articles explicitly say so, and I can't find any that do.
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1So a key point here is that the manufactured proteins are not attacked by the immune system as discrete particles but as surface features of a cell. Commented May 20, 2021 at 23:07
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It's barely known that viral antigen/m-RNA-antigen can be become a "surface feature" in a narrow sense as it may be expressed outside the so called - immunizing - MHC. I cannot tell if CoV-19 is some special case, I found it surprising that infected cells use viral antigen as somehow "handy" "surface feature" for cell to cell signaling (search word is syncytium, syncytia, I recommend). Commented Mar 25, 2022 at 13:10
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One way to ask may be: Is presentation to immune cell on surface (on MHC that is) the effect or the cause of immanent cell death? Alternatively, if you delete all killer cells will a cell that presents antigen on its surface (in MHC context) survive? My idea I consider some paradox: The more symbiotic the viral infection and the interaction with the host is the more it is necessary to have killer cells attracted to that site to stop this (The less viral infection as such leads to cell death the more the killing is needed, the more the presentation on MHC seems against single cell's will.) Commented Mar 25, 2022 at 13:15
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Also, I want to draw the attention to some basic understanding: what is need for immunity to arise is "priming". That word is rarely heard, in contrast to "presentation" - you say "surface feature" which is pleasing. Commented Mar 25, 2022 at 13:19