Thread on why mRNA vaccines may be giving better immunity vs. SARS-CoV-2 than surviving natural infection.
disclaimer: we still don't understand the long-term correctness of the claim that vaccines are better protection than natural infection.
TL;DR: it's different kind of vax
disclaimer: we still don't understand the long-term correctness of the claim that vaccines are better protection than natural infection.
TL;DR: it's different kind of vax
In this thread I will offer some speculation as to why it's scientifically plausible that the vaccines offer better protection than surviving natural infection.
This is what it is, speculation.
As I said in the parent tweet, it remains to be seen how true this phenomenon is.
This is what it is, speculation.
As I said in the parent tweet, it remains to be seen how true this phenomenon is.
cont'd
But if it is true, I don't think it defies logic. And here I will explain why.
But if it is true, I don't think it defies logic. And here I will explain why.
The virus is like a beach ball with spikes attached.
The immune system builds antibodies that bind to the virus. In theory, any part of the virus, but in practice the immune binding target for viruses like this is usually the spike protein, and not just any part of the spike...
The immune system builds antibodies that bind to the virus. In theory, any part of the virus, but in practice the immune binding target for viruses like this is usually the spike protein, and not just any part of the spike...
cont'd
... but the dominant epitope.
So the whole virus presents itself to the immune system, but the spike protein dominant epitope is to what we make antibodies. And it works. Antibodies bind the spike protein and neutralize the virus. ...
... but the dominant epitope.
So the whole virus presents itself to the immune system, but the spike protein dominant epitope is to what we make antibodies. And it works. Antibodies bind the spike protein and neutralize the virus. ...
cont'd
The problem is that the dominant epitope may evolve and then the old antibodies don't bind as well... and immunity is imperfect.
Why doesn't immune system make antibodies to different parts of the spike protein, that might evolve less rapidly than the dominant epitope?
The problem is that the dominant epitope may evolve and then the old antibodies don't bind as well... and immunity is imperfect.
Why doesn't immune system make antibodies to different parts of the spike protein, that might evolve less rapidly than the dominant epitope?
cont'd
Well, there are a lot of mysteries of immune system. But remember that with wild virus, immune system is seeing the whole "beach ball". The base of spike protein is attached to virus membrane, which is therefore subject to all sorts of electrostatic forces and so on.
Well, there are a lot of mysteries of immune system. But remember that with wild virus, immune system is seeing the whole "beach ball". The base of spike protein is attached to virus membrane, which is therefore subject to all sorts of electrostatic forces and so on.
cont'd
These electrostatic forces, which are greatly a function of the conformational geometry and chemistry of the virus, probably play a role in steering the immune response to the dominant epitope. This is all in the case of natural infection...
These electrostatic forces, which are greatly a function of the conformational geometry and chemistry of the virus, probably play a role in steering the immune response to the dominant epitope. This is all in the case of natural infection...
cont'd
Well with the mRNA vaccines, it's different. The vaccine prompts our cells to manufacture copies of the viral spike protein, which our immune system then sees.
But now it's seeing spike protein alone, not attached to the beach ball. So the electrostatics are different.
Well with the mRNA vaccines, it's different. The vaccine prompts our cells to manufacture copies of the viral spike protein, which our immune system then sees.
But now it's seeing spike protein alone, not attached to the beach ball. So the electrostatics are different.
cont'd
So the dominant epitope of the spike protein as presented to the immune system may be different for the vaccine than for natural infection. And in fact it's possible that immune system is creating antibodies to multiple sites on the spike protein, in response to mRNAvax.
So the dominant epitope of the spike protein as presented to the immune system may be different for the vaccine than for natural infection. And in fact it's possible that immune system is creating antibodies to multiple sites on the spike protein, in response to mRNAvax.
cont'd
So then when presented (post- mRNAvax) with SARS-CoV-2, the immune system potentially has a catalog of MULTIPLE antibody target sites on the spike protein, not just for the dominant epitope in its prior phenotype.
So then when presented (post- mRNAvax) with SARS-CoV-2, the immune system potentially has a catalog of MULTIPLE antibody target sites on the spike protein, not just for the dominant epitope in its prior phenotype.
cont'd
Since not all of these would-be binding sites on the spike protein are likely to have evolved, the immune system has a greater chance, with its larger catalog of candidate antibodies.
If the antibody is already there, it would seem, electrostatics be damned. It binds...
Since not all of these would-be binding sites on the spike protein are likely to have evolved, the immune system has a greater chance, with its larger catalog of candidate antibodies.
If the antibody is already there, it would seem, electrostatics be damned. It binds...
cont'd
... and neutralizes.
Yes, without vaccine, immune system would tend to make antibodies to spike protein dominant epitope, but post-vax, it now has a bunch of binding antibodies that would never have been available if it had not already seen spike protein in isolation.
... and neutralizes.
Yes, without vaccine, immune system would tend to make antibodies to spike protein dominant epitope, but post-vax, it now has a bunch of binding antibodies that would never have been available if it had not already seen spike protein in isolation.
cont'd
Is this exactly why vaccination gives better protection in this case, vs surviving infection?
Well we don't even know if this is true in long run, so it could be an explanation for a non-existent phenomenon.
I'm just trying to say, if true: it doesn't defy all logic.
Is this exactly why vaccination gives better protection in this case, vs surviving infection?
Well we don't even know if this is true in long run, so it could be an explanation for a non-existent phenomenon.
I'm just trying to say, if true: it doesn't defy all logic.
Thank you for reading my thread on covid vaccination, and why it might (might!) be working better than surviving natural infection.
Alas, I can't offer you a Krispy Kreme.
Alas, I can't offer you a Krispy Kreme.
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