That is a good explanation. Antibody titers are high enough that a 10 fold reduction in efficacy is made up for by the sheer numbers of antibodies. Titers also seem to be stable over several months:
As titers fall over time there may be higher risk from some variants, but all variants will be risky at some point in time.
Thanks for the correction.
No, nothing we’ve learned in the last few weeks suggests that ADE is more likely. Lowe’s post from a week ago, linked above, shows that there’s not even a hint of ADE.
Let’s test your claim of understanding vaccines. What would the graphs I posted earlier today look like if E484K was eliciting ADE, Gil?
What about your claim that the chimeric transcripts are relevant to vaccines? You still haven’t explained that one yet.
Indeed. The fact that some variants are less susceptible to neutralizing Abs tells us that we need to vaccinate worldwide as soon as possible, to avoid additional new ones evolving under immune pressure.
There are 2 other factors besides neutralizing antibody that are much harder to measure: clonal maturation, discussed by Lowe at the link above; and cellular immunity.
You’re welcome. It’s a relief to be wrong in that direction. I have never enjoyed being wrong as much as I did when I saw the efficacy data from the mRNA vaccines.
Wait, what? Laugh or cry?
Why? That seems nuts.
Are you convinced that mutation will lead to higher reinfections based on what you’ve seen?
Sometimes you have to laugh while crying.
Why what? Why are they rejected? Because the databases have automated filters to screen out mis-assembled genomes. You can get around the filters but it takes a bit of extra effort (which not all labs will do, especially if they’re sequencing at high volume) and slows things down.
I don’t think there’s enough data to say how much practical effect the immune evasion mutations will have. The mutations conferring higher transmissibility (which our local lineage doesn’t have, fortunately) have a real and large effect.
As far as I can tell, the authors assessed the neutralizing activity of the vaccine sera on Vero E6 cells, which is not the right model to probe ADE for they don’t express Fc receptors. So to answer your question, the graphs you refer to would look the same with or without ADE.
Very good! And what should they look like if we expressed FcRs or cocultured with cells that naturally express them?
And why, given the difference in reactivity between vaccine-elicited and infection-elicited neutralizing antibody against E84K, should there be any concern about the vaccine other than to speed up its use?
There may be several concerns. For example:
This being said, until now, it is true that things seems to go well, as the post below shows, and this is good news.
For an N of only 3, those titers are remarkably consistent, so I would bet that if you titered the sera of 100 other vaccinated people, 70% would fall within that range. Keep in mind that the titers from infected people are all over the place.
You do realize that the immune response is not limited to neutralizing antibodies, don’t you? They’re just the easiest to measure.
Which is why everyone around the world needs to be vaccinated ASAP.
I do, however, dispute your assumption that ADE is in any way a result of escaping neutralization. They could occur simultaneously, since the antibody response is polyclonal.
So…this is the kind of thing I think that makes national news. How far up the chain is the government aware? It seems that this could have a huge effect on not understanding the variants correctly, which in turn affects public policy.
I don’t think it’s quite that serious – most groups that are sequencing will look for known worrisome mutations in their own data. And we have let the CDC know and are spreading the word among sequencers.
I think there ought to be some action on the part of the mods to tamp down on the covid misinformation in here.
This conversation has run it’s course.