I was wondering, is it possible for the isolated spike protein, as resulting from an mRNA vaccine, to cause harmful side effects in an individual, that would not have developed in that individual if it had been exposed to the actual virus? I am wondering about the spike protein in particular, i.e. I am specifically excluding any other compounds contained in a vaccine, but I would include "side-effects" caused by the spike protein of the actual virus.

The only way I could imagine this to be the case, if by being isolated and this being quite a lot smaller compared to a whole virus, the protein could find its way into areas of the body where it could "fit" otherwise.

Am I correct in assuming that the side effects that had been observed so far for these vaccines could be explained by an individuals immune reaction, rather than the spike protein itself?


1 Answer 1


In both infection by the virus and mRNA-mediated expression of the spike protein, spike proteins are produced in the host cell as membrane-bound proteins; they're not just separate particles floating around. Whether or not the rest of the viral machinery is present, these will end up displayed in the membrane of the infected cells. Here's a diagram showing that process in infection (note the little "blue spikes" in the cell membrane at the far right):

enter image description here

Figure from Duan, L., Zheng, Q., Zhang, H., Niu, Y., Lou, Y., & Wang, H. (2020). The SARS-CoV-2 spike glycoprotein biosynthesis, structure, function, and antigenicity: Implications for the design of spike-based vaccine immunogens. Frontiers in immunology, 11, 2593.

B-cells will recognize these foreign antigens, again whether their production was initiated by the virus or by a vaccine (here the equivalent of the "blue spikes" in the first figure are the "green S protein"):

Immune recognition of antigens

Figure from Teijaro, J. R., & Farber, D. L. (2021). COVID-19 vaccines: modes of immune activation and future challenges. Nature Reviews Immunology, 21(4), 195-197.

(note: don't be fooled by the separate mRNA and AdV vaccine strategies here; the outcomes and mechanisms are the same, the diagram is just condensed to show both in one figure)

With mRNA vaccines, production of spike proteins is limited in time and space: to the cells that take up the injected mRNA, and only until that mRNA is degraded.

With normal infection, production of spike proteins is only limited by the course of the infection: as long as the virus continues to replicate, spike proteins will be produced in the membranes of affected cells, and can be produced anywhere in the body that the virus spreads (though principally in the respiratory compartments where the virus preferentially infects).


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