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A layman's take: Maybe the antibodies are different because the immune system is being presented with _only_ the spike protein, rather than the whole virus? F

A layman's take: Maybe the antibodies are different because the immune system is being presented with _only_ the spike protein, rather than the whole virus? From my understanding, the immune system breaks the viral proteins up into pieces and then starts rapidly "evolving" antibodies to target those pieces. The goal being to ultimately produce antibodies that target those pieces, and don't target the learned whitelist of proteins (from your own body). Once it's got that it begins deploying antibody producing cells, and remembers the antibodies for later infections. What I'm curious about is the stopping criteria the body uses during the evolution stage. It sounds like it's producing an array of antibodies, not just one kind. So the stopping criteria isn't finding one working antibody. Perhaps it's more like, "Produce at least N different antibodies." If the latter, then the difference between natural and mRNA immunity makes sense to me. If your immune system is working to produce N different antibodies for the whole viral proteome, less of those antibodies will target the spike protein. And thus it will have less resilience to changes in the spike protein. But of course more tolerance to changes in the virus as a whole. Whereas with mRNA the immune system only sees the spike proteins, and since it's still going to make N different antibodies it'll have more tolerance for changes to the spike protein. What's most interesting to me, assuming any of the above is close to reality, is that mRNA vaccines allow us to give our immune system an inductive bias of some kind. Presumably our immune systems aren't "smart" enough to know what parts of a virus are most conserved, and thus best to target. It just targets all of it blindly. mRNA vaccines used the spike protein because we believe that to be the most conserved proteins. If those change too much the virus either won't work, or will effectively be a different species. So our mRNA vaccines are a way of telling our immune systems to focus their work on the "important" proteins, and thus, we would assume, give us better immunity. Whether our guess about the spike proteins is correct remains to be seen I suppose.

IX-103 5y ago
It's not "make N antibodies". It's a bunch of cells in parallel creating cells specialized to each create a single random antibody. Cells that create antibodies that don't work don't reproduce (linear decay). Cells that create antibodies that worked reproduce (exponential growth). This process stops when the infection is gone. For the mRNA vaccines, the antibodies only target the some protein, but on the other hand they all target the spike protein. Natural immunity products antibodies that could match want part oft the virus. The amount of protection you get against a new variant is related to how well your existing antibodies match the new virus. With natural immunity it is likely that only some of the antibodies match (and since each antibody exists in random amounts, the matching antibodies may be the ones that you have much less of). With vaccine immunity,all of the antibodies produced will work against the new variant if the spike protein is the same, offering nearly the same immunity to the variant as the original virus (assuming the spike protein doesn't change significantly). We know that the spike protein is significantly less likely to change than other parts of the virus so that's a reasonable assumption.
criticaltinker 5y ago
Solid layman reasoning, just wanted to clear up one slight misconception: > mRNA vaccines used the spike protein because we believe that to be the most conserved proteins The spike protein was chosen mostly because it was well known to serve a primary role in the process of infection and subsequent immune response. Ongoing vaccine research is exploring the use of additional proteins, because they have been demonstrated to be a major factor in viral replication and protective immunity. For example, nucleocapsid (N) protein antibodies are induced by natural infection, but not by vaccination using the current solely spike protein focused mRNA vaccine formulations. N protein antibodies likely have a synergistic effect with S protein antibodies, and thus vaccine formulations incorporating both elements may result in more robust protection, especially against variants. See my other comment on this thread for supporting excerpts and citations from the literature. [1] https://news.ycombinator.com/item?id=28320340 https://news.ycombinator.com/item?id=28320340

IX-103 5y ago

It's not "make N antibodies". It's a bunch of cells in parallel creating cells specialized to each create a single random antibody. Cells that create antibodies that don't work don't reproduce (linear decay). Cells that create antibodies that worked reproduce (exponential growth). This process stops when the infection is gone. For the mRNA vaccines, the antibodies only target the some protein, but on the other hand they all target the spike protein. Natural immunity products antibodies that could match want part oft the virus. The amount of protection you get against a new variant is related to how well your existing antibodies match the new virus. With natural immunity it is likely that only some of the antibodies match (and since each antibody exists in random amounts, the matching antibodies may be the ones that you have much less of). With vaccine immunity,all of the antibodies produced will work against the new variant if the spike protein is the same, offering nearly the same immunity to the variant as the original virus (assuming the spike protein doesn't change significantly). We know that the spike protein is significantly less likely to change than other parts of the virus so that's a reasonable assumption.

criticaltinker 5y ago

Solid layman reasoning, just wanted to clear up one slight misconception: > mRNA vaccines used the spike protein because we believe that to be the most conserved proteins The spike protein was chosen mostly because it was well known to serve a primary role in the process of infection and subsequent immune response. Ongoing vaccine research is exploring the use of additional proteins, because they have been demonstrated to be a major factor in viral replication and protective immunity. For example, nucleocapsid (N) protein antibodies are induced by natural infection, but not by vaccination using the current solely spike protein focused mRNA vaccine formulations. N protein antibodies likely have a synergistic effect with S protein antibodies, and thus vaccine formulations incorporating both elements may result in more robust protection, especially against variants. See my other comment on this thread for supporting excerpts and citations from the literature. [1] https://news.ycombinator.com/item?id=28320340 https://news.ycombinator.com/item?id=28320340