[majormajor]

> The vaccine is ~95% effective. This means you're going to have a lot of people get infected still with the vaccine's antibodies present; any mutation that happens that causes escape from these antibodies will prolong disease and increase transmission, even if that mutation renders the virus a bit less fit in a non-vaccinated host.

Is that an accurate summation of those who caught it after receiving the vaccine?

Seems like if 5% of virus strains circulating aren't affected by the vaccine, we're fucked anyway. That 5% will become 100% of what's circulating in the next year and will be ubiquitous?

If it's something like "5% of people don't respond to the vaccine to build antibodies at all," on the other hand, it's much rosier...

[mlyle]

It's more like 5% of people don't build as many or as effective of antibodies to the vaccine spike protein, and then when infected are petri dishes providing selective pressure for variants to mutate that escape these antibodies and become dominant within their bodies (and, in turn, are more readily transmitted to vaccinated people around them).

Some of the 5% may just be unlucky people who got bigger doses of the virus/higher initial infectious dose, but the same logic applies.

It may be more than 5%, even; the vaccine likely does more to prevent symptomatic illness than infection.

It's hard to estimate what the probability of this happening is. It's certainly more likely when there's more illness circulating around-- e.g. if 1 million people with the vaccine become infected it's worse than if it's 10,000.

[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]

> 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.