[majormajor]

> 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]

> 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]

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]

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]

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]

> 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.

I disagree. You have the weak vaccine response the entire duration of infection applying selective pressure. What you say seems to disagree with the consensus of the literature, e.g.

https://www.medrxiv.org/content/10.1101/2020.11.17.20233726v...

> The UK variant isn't better at evading the immune system from what we know. It's simply more infectious in general.

The mutations have been broadly described as "immune escape mutations" and are thought to have emerged from pressure to escape low numbers of existing sterilizing antibodies within the host, e.g.

"The unusually high number of spike protein mutations, other genomic properties of the variant, and the high sequencing coverage in the UK suggest that the variant has not emerged through gradual accumulation of mutations in the UK. It is also unlikely that the variant could have arisen through selection pressure from ongoing vaccination programmes as the observed increase does not match the timing of such activities. One possible explanation for the emergence of the variant is prolonged SARS-CoV-2 infection in a single patient, potentially with reduced immunocompetence, similar to what has previously been described [17,18]. Such prolonged infection can lead to accumulation of immune escape mutations at an elevated rate"

https://www.ecdc.europa.eu/sites/default/files/documents/SAR...

[sudosysgen]

The article you linked first assumes only one or two antibodies.

As I said before, there is some pressure for antibodies, but the immune system is way more than that, and people can clear infections very effectively without any antibodies at all.

As for your other link, it's important to know that this a preliminary article that, on those subjects, gives ideas without data. Further research has shown that this variant does not seem to increase disease severity, and instead is just more infectious, as the spike protein evolved for higher binding affinity.

[mlyle]

> 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]

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]

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.