'And past antibodies, there's the whole T-cell system - those T cells are looking to recognize human cells that have been attacked by the virus, whereupon they move in to kill them off before they can break open like a piñata and release a big pile of new viral particles. They are primed for this task by having pieces of viral proteins presented to them by other immune cells, and these T cells become specifically sensitized to the appearance of these in the future - these pieces get taken to the surface of infected cells by the MHC glycoproteins where the T cells can detect them. So you can see that in all of these cases, the key is protein surface recognition, which tells you how viruses can work their way around to evading such attacks. They have to change their surface proteins in such a way that they can still function, but that defeats that antibody/T-cell binding that the immune system has settled in on.
That's not so easy, because (for one thing) there are an enormous number of different antibodies involved (and an enormous number of T-cell recognition proteins). There are any number of ways to bind to a given protein target, and the adaptive immune system's whole function is to be ready for all kinds of targets and to hit them in all kinds of ways. And there's that constraint mentioned above: the virus still has to be able to function! Losing the entire Spike protein or mutating it completely beyond recognition would definitely evade vaccine-induced immunity, but it would also definitely produce a coronavirus that couldn't infect human cells in the way it's completely evolved to do. Coming up with a completely new infection route is (mutationally) extremely costly and complex, and not something that can be done "on the fly". Various coronaviruses use different human cell surface proteins to do their attack, but these have gradually developed and diverged over evolutionary time (hundreds of thousands, or millions of years) through untold numbers of tiny steps.
But it can be done, in principle. And as with everything in evolution, if it gets done at all, it'll get done by similarly untold numbers of individual mutants, and mutants on top of those mutants, until something appears that can both avoid being inactivated by the immune response and still infect cells and reproduce. There is no guarantee that such a virus can exist, and there is no guarantee that it can't. Evaluating the number of possibilies is frankly beyond computation - we didn't, for example, see the details of the Delta variant coming, and if you'd given someone that exact sequence last year, there's no guarantee that they would have been able to predict how much more infectious it would be.
The more chances you give the coronavirus to reproduce, the more mutations it will explore. Its proofreading system for reproduction is pretty good but not perfect, and that's where the mutations come from. It's a numbers game all the way. The virus is not thinking about how to evade vaccine-induced immunity; it's throwing stuff randomly against every available wall in every available direction, and whatever sticks gets a chance to go on throwing some more. Remember, an unvaccinated person is still mounting an antibody defense against the virus - they're just having to do it from scratch, rather than having a pre-primed leg up like someone who's been vaccinated. The longer these infections go on inside human bodies, the more bets the virus gets to put down on the table. The good news is that so far, there is not much evidence that the virus is doing much evasion inside a given person during the course of normal infection.
So one key way to cut down on the odds of a nasty mutant popping up is to just keep the virus from reproducing so much. Cut down on the number of people it infects. When it does infect people, cut down on the amount of time it spends reproducing inside the body. These countermeasures are exactly what a mass vaccination program does. Fewer people get infected in the first place, and when they do get infected, their disease course tends in the great majority of cases to be shorter and milder. A nasty variant is almost certainly going to come up by accident, so let's not have so many accidents going on constantly around the clock, around the world.
...
a true vaccine-evading mutant is going to need a set of several mutations (off the existing variants) all at the same time. The vaccine-induced immune response looks like it's knocking down a lot of these intermediate-step mutations before they can keep on throwing off subsequent mutations on top of the first ones. These pathways are choked off before they can even get explored, and this "evolutionary smothering" is something that you don't see so dramatically when you're doing those in vitro experiments with specifically targeted small molecules mentioned at the top of this post. A broad antibody and T-cell response is a different thing altogether.
There is, then, every reason at both the population and individual level to expect that vaccination will strongly decrease the chances of a more dangerous coronavirus strain taking hold. If we'd had them earlier and were able to deploy them quickly and widely enough, we never would have seen the Delta variant in the first place. If we keep deploying them now, we will keep worse variants from even being able to form. Anyone who tells you that vaccines will make things worse is at best deeply misinformed and at worst lying to you for profit.'
https://www.science.org/content/blog-post/vaccines-will-not-produce-worse-variants
That's not so easy, because (for one thing) there are an enormous number of different antibodies involved (and an enormous number of T-cell recognition proteins). There are any number of ways to bind to a given protein target, and the adaptive immune system's whole function is to be ready for all kinds of targets and to hit them in all kinds of ways. And there's that constraint mentioned above: the virus still has to be able to function! Losing the entire Spike protein or mutating it completely beyond recognition would definitely evade vaccine-induced immunity, but it would also definitely produce a coronavirus that couldn't infect human cells in the way it's completely evolved to do. Coming up with a completely new infection route is (mutationally) extremely costly and complex, and not something that can be done "on the fly". Various coronaviruses use different human cell surface proteins to do their attack, but these have gradually developed and diverged over evolutionary time (hundreds of thousands, or millions of years) through untold numbers of tiny steps.
But it can be done, in principle. And as with everything in evolution, if it gets done at all, it'll get done by similarly untold numbers of individual mutants, and mutants on top of those mutants, until something appears that can both avoid being inactivated by the immune response and still infect cells and reproduce. There is no guarantee that such a virus can exist, and there is no guarantee that it can't. Evaluating the number of possibilies is frankly beyond computation - we didn't, for example, see the details of the Delta variant coming, and if you'd given someone that exact sequence last year, there's no guarantee that they would have been able to predict how much more infectious it would be.
The more chances you give the coronavirus to reproduce, the more mutations it will explore. Its proofreading system for reproduction is pretty good but not perfect, and that's where the mutations come from. It's a numbers game all the way. The virus is not thinking about how to evade vaccine-induced immunity; it's throwing stuff randomly against every available wall in every available direction, and whatever sticks gets a chance to go on throwing some more. Remember, an unvaccinated person is still mounting an antibody defense against the virus - they're just having to do it from scratch, rather than having a pre-primed leg up like someone who's been vaccinated. The longer these infections go on inside human bodies, the more bets the virus gets to put down on the table. The good news is that so far, there is not much evidence that the virus is doing much evasion inside a given person during the course of normal infection.
So one key way to cut down on the odds of a nasty mutant popping up is to just keep the virus from reproducing so much. Cut down on the number of people it infects. When it does infect people, cut down on the amount of time it spends reproducing inside the body. These countermeasures are exactly what a mass vaccination program does. Fewer people get infected in the first place, and when they do get infected, their disease course tends in the great majority of cases to be shorter and milder. A nasty variant is almost certainly going to come up by accident, so let's not have so many accidents going on constantly around the clock, around the world.
...
a true vaccine-evading mutant is going to need a set of several mutations (off the existing variants) all at the same time. The vaccine-induced immune response looks like it's knocking down a lot of these intermediate-step mutations before they can keep on throwing off subsequent mutations on top of the first ones. These pathways are choked off before they can even get explored, and this "evolutionary smothering" is something that you don't see so dramatically when you're doing those in vitro experiments with specifically targeted small molecules mentioned at the top of this post. A broad antibody and T-cell response is a different thing altogether.
There is, then, every reason at both the population and individual level to expect that vaccination will strongly decrease the chances of a more dangerous coronavirus strain taking hold. If we'd had them earlier and were able to deploy them quickly and widely enough, we never would have seen the Delta variant in the first place. If we keep deploying them now, we will keep worse variants from even being able to form. Anyone who tells you that vaccines will make things worse is at best deeply misinformed and at worst lying to you for profit.'
https://www.science.org/content/blog-post/vaccines-will-not-produce-worse-variants
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