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> It's more like 5% of people don't build as many or as effective of antibodies to the vaccine spike protein, and then are petri dishes providing selective pre

> It's more like 5% of people don't build as many or as effective of antibodies to the vaccine spike protein, and then are petri dishes providing selective pressure for viruses that escape these antibodies. This seems very circular to me. If they don't build very effective antibodies, they shouldn't be putting much selective pressure on the virus, because if they did, they'd be more effective in the first place. I suppose it depends on how exactly "effective" plays out here, as well as how easy it is for the virus to mutate significantly but stay as contagious as it is, but if we get unlucky it seems like just a question of time for it to get bad. Given Jan-Mar 2019, I have little faith that the US would ever be in a position to fully eradicate even a small remaining bit, and it would instead fester and mutate in this scenario until exploding again. Maybe multiple vaccines mitigates this a bit...

mlyle 6y ago
> This seems very circular to me. If they don't build very effective antibodies, they shouldn't be putting much selective pressure on the virus, because if they did, they'd be more effective in the first place. If a normal person generates a dozen types of antibodies to the vaccine's spike protein, and a couple types are strongly sterilizing... And you happen to have an immune response where you generate 8/12 of these, and only one of the strongly sterilizing variant, and you are more prone to become infected as a result... Then, once infected, the virus will be under selective pressure during your illness to escape some of those 8 antibodies. In turn, whomever you spread it to will have a harder time. > Maybe multiple vaccines mitigates this a bit... Maybe. But the portion of the spike protein they're expressing and the resulting antibody profiles look very similar. > Given Jan-Mar 2019, I have little faith that the US would ever be in a position to fully eradicate even a small remaining bit, and it would instead fester and mutate in this scenario until exploding again. Yes, but one silver lining is that there would still be some immunity / cross-reactivity / t cell mediated immunity, etc. People would still be less likely to have severe illness, I believe.
- sudosysgen 6y ago
  It's a lot more complex than that. Immune responses are a lot more complex than antibodies. People can actually get rid of an infection before they have a lot of antibodies. The virus in this case would have to evolve in your body to escape not just 4-6 of the 12 antibodies, but most of them, otherwise it still won't be able to cause productive infections before it starts getting neutralized and the immune system detecting neutralized viruses mounts a stronger response.
  - mlyle 6y ago
    Yes. I know immunology is way more complicated than I understand, and that I'm oversimplifying even from my level of understanding. There's all kinds of immune responses we're interested in here. However, sterilizing antibodies are most interesting because they are the strongest factor in preventing transmission. People with weak immune responses of various kinds can be expected to have more infections and to be infected for longer times, and they provide selective pressure to evade the remaining mechanisms.
mlyle 6y ago
> This seems very circular to me. If they don't build very effective antibodies, they shouldn't be putting much selective pressure on the virus, because if they did, they'd be more effective in the first place. Just to follow up / argue from another angle. It's believed to be likely that the "new" UK variant likely emerged in an immunocompromised individual. This results in A) -some- immune response, and B) prolonged infection where the virus is under evolutionary pressure to escape that immune response / original antibodies. Someone who doesn't mount a strong response to the vaccine is a very similar case.
- sudosysgen 6y ago
  Not really, because they can still mount a strong response from the infection. The immune system is a lot more than just antibodies. Even a weak response to the vaccine can activate bound antibody responses during challenge, which means the immune system is activated much faster and even though there is still infection it is much shorter, leaving less of a chance for the virus to mutate.
  - mlyle 6y ago
    Sure. Even a partial response from a vaccine suppresses the virus and (usually) reduces the risk of transmission. At the same time, it creates a window where the virus is under selective pressure to escape some of the immune response from the vaccine's effects. Individuals who have smaller/partial responses to the vaccine are more likely to have this happen. That is all I'm saying, and I don't think it's really that controversial. I'm not trying to make a robust immunological argument. I don't think it's inevitable, but it's another reason to reduce transmission. We already have the UK variant, which many have suggested is better at immune escape due to perhaps evolving during a long infection in an immunocompromised individual.
    - sudosysgen 6y ago
      Selective responses against the vaccine are only selected for if those pressures persist during replication. It's not enough to have that pressure at the very beginning, it needs to persist all the way. This isn't really the case for a vaccine. In other words, by the time the virus is replicating inside of you, it doesn't really have much pressure to evolve to evade those other facets of vaccine immunity, because doing so would probably hurt it. The UK variant isn't better at evading the immune system from what we know. It's simply more infectious in general.

mlyle 6y ago

> This seems very circular to me. If they don't build very effective antibodies, they shouldn't be putting much selective pressure on the virus, because if they did, they'd be more effective in the first place. If a normal person generates a dozen types of antibodies to the vaccine's spike protein, and a couple types are strongly sterilizing... And you happen to have an immune response where you generate 8/12 of these, and only one of the strongly sterilizing variant, and you are more prone to become infected as a result... Then, once infected, the virus will be under selective pressure during your illness to escape some of those 8 antibodies. In turn, whomever you spread it to will have a harder time. > Maybe multiple vaccines mitigates this a bit... Maybe. But the portion of the spike protein they're expressing and the resulting antibody profiles look very similar. > Given Jan-Mar 2019, I have little faith that the US would ever be in a position to fully eradicate even a small remaining bit, and it would instead fester and mutate in this scenario until exploding again. Yes, but one silver lining is that there would still be some immunity / cross-reactivity / t cell mediated immunity, etc. People would still be less likely to have severe illness, I believe.

sudosysgen 6y ago
It's a lot more complex than that. Immune responses are a lot more complex than antibodies. People can actually get rid of an infection before they have a lot of antibodies. The virus in this case would have to evolve in your body to escape not just 4-6 of the 12 antibodies, but most of them, otherwise it still won't be able to cause productive infections before it starts getting neutralized and the immune system detecting neutralized viruses mounts a stronger response.
- mlyle 6y ago
  Yes. I know immunology is way more complicated than I understand, and that I'm oversimplifying even from my level of understanding. There's all kinds of immune responses we're interested in here. However, sterilizing antibodies are most interesting because they are the strongest factor in preventing transmission. People with weak immune responses of various kinds can be expected to have more infections and to be infected for longer times, and they provide selective pressure to evade the remaining mechanisms.

mlyle 6y ago

> This seems very circular to me. If they don't build very effective antibodies, they shouldn't be putting much selective pressure on the virus, because if they did, they'd be more effective in the first place. Just to follow up / argue from another angle. It's believed to be likely that the "new" UK variant likely emerged in an immunocompromised individual. This results in A) -some- immune response, and B) prolonged infection where the virus is under evolutionary pressure to escape that immune response / original antibodies. Someone who doesn't mount a strong response to the vaccine is a very similar case.

sudosysgen 6y ago
Not really, because they can still mount a strong response from the infection. The immune system is a lot more than just antibodies. Even a weak response to the vaccine can activate bound antibody responses during challenge, which means the immune system is activated much faster and even though there is still infection it is much shorter, leaving less of a chance for the virus to mutate.
- mlyle 6y ago
  Sure. Even a partial response from a vaccine suppresses the virus and (usually) reduces the risk of transmission. At the same time, it creates a window where the virus is under selective pressure to escape some of the immune response from the vaccine's effects. Individuals who have smaller/partial responses to the vaccine are more likely to have this happen. That is all I'm saying, and I don't think it's really that controversial. I'm not trying to make a robust immunological argument. I don't think it's inevitable, but it's another reason to reduce transmission. We already have the UK variant, which many have suggested is better at immune escape due to perhaps evolving during a long infection in an immunocompromised individual.
  - sudosysgen 6y ago
    Selective responses against the vaccine are only selected for if those pressures persist during replication. It's not enough to have that pressure at the very beginning, it needs to persist all the way. This isn't really the case for a vaccine. In other words, by the time the virus is replicating inside of you, it doesn't really have much pressure to evolve to evade those other facets of vaccine immunity, because doing so would probably hurt it. The UK variant isn't better at evading the immune system from what we know. It's simply more infectious in general.