[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]

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

Assumes only a couple of neutralizing antibodies, which is fair for the vaccine candidates-- immune assays of Moderna's vaccine show two typical antibody binding sites against the RBD that are strongly neutralizing. I haven't seen the ELISA data for Pfizer's vaccine.

Given that we've got several papers describing how immune escape variants of other viruses have emerged in the past... I'm curious why you don't think it's much of a risk here?

e.g. https://pubmed.ncbi.nlm.nih.gov/11410701/

> 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.

Of course. I'm not speculating that there's going to be some nasty variant that completely eludes our immune response. I'm saying that it is likely-- and the consensus opinion-- that there is a real risk that the virus mutates to render the vaccine less effective.

> 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.

Some of the mutations slightly increase binding affinity. Other deletions look like their primary fitness advantage is immune escape. A missing stop-codon also increases mutation rates for a portion of the RBD, which implies we can expect quicker emergence of subvariants.

It's like you're having an argument I never was having: I have never said that this is likely to cause more severe disease. I am just saying that the virus will be under selective pressure to evade the vaccine-induced immune responses-- which is something I think everyone agrees. This is less likely to happen if there's less infection around and people get vaccinated quicker.

Even in the worst case, where such a variant evolves quickly-- I don't think we're that bad off. As you mention, there's other immune responses. Strong T cell mediated immunity will almost certainly be cross-reactive and strongly reduce the risk of severe illness. We'll have more time to adjust vaccines without mortality accruing as quickly. It is still something we'd prefer to avoid at all costs.