Nice, that’s reassuring. I assumed that claim (2) was basic immunology because he was talking about it so confidently, but at the same time, I noticed confusion about the lack of precedents where outdated antibodies (from previous infection or outdated flu vaccines) cause complications. It seems like immunologists think his view on (2) are outlandish – in which case, “case closed, nothing to see here.”
Edit: On the other hand, reading this blogpost makes me think that the mechanism Vanden Bossche proposes is plausible at least in theory. But also, the Nature blogpost discusses that targeting the spke protein in particular was a good idea:
Targeting the Spike protein is another big benefit that we got from the earlier SARS work; which suggested that (for example) targeting the Nucleocapsid (N) protein was riskier. With the Spike, you put the virus in an evolutionary tight spot: evading the antibodies while trying not to lose the ability to bind to the human ACE2 protein. So far, that looks like too narrow a path for the virus to stumble through.
So far, that all seems right and the vaccines continue to be functional enough to neutralize even the most vaccine-resistant variants.
Yeah, his second claim is bogus. That’s not how it works, and that’s not what we’ve been seeing with existing mutations.
As an example, look at E484K—this mutation changes the amino acid polarity, so that antibodies trained against the E variant will have a much harder time attaching to the K variant. If an antibody fails to attach, it doesn’t ‘crowd out’ anything.
In the case where an antibody attaches but doesn’t actually “inactivate” the virus due to a mutation, that’s because the virus’ attack surfaces are still present and exposed (otherwise, it would be inactivated.) Again, we wouldn’t expect to see “crowding out” of other antibodies.
And lastly, there’s the extremely unlikely scenario of sufficient mutation that existing antibodies give us Vaccine Enhanced Disease. This is both something vaccine designers explicitly focus on to minimize the risk of, and would require an extreme amount of change to enable.
As an example, look at E484K—this mutation changes the amino acid polarity, so that antibodies trained against the E variant will have a much harder time attaching to the K variant. If an antibody fails to attach, it doesn’t ‘crowd out’ anything.
That makes sense; I was wondering about this exact thing. It seems like VB is painting a worst-case scenario where a bunch of things go wrong in a specific way. Perhaps not impossible, but based on what you’re saying, there’s no reason to be unusually concerned.
Nice, that’s reassuring. I assumed that claim (2) was basic immunology because he was talking about it so confidently, but at the same time, I noticed confusion about the lack of precedents where outdated antibodies (from previous infection or outdated flu vaccines) cause complications. It seems like immunologists think his view on (2) are outlandish – in which case, “case closed, nothing to see here.”
Edit: On the other hand, reading this blogpost makes me think that the mechanism Vanden Bossche proposes is plausible at least in theory. But also, the Nature blogpost discusses that targeting the spke protein in particular was a good idea:
So far, that all seems right and the vaccines continue to be functional enough to neutralize even the most vaccine-resistant variants.
Yeah, his second claim is bogus. That’s not how it works, and that’s not what we’ve been seeing with existing mutations.
As an example, look at E484K—this mutation changes the amino acid polarity, so that antibodies trained against the E variant will have a much harder time attaching to the K variant. If an antibody fails to attach, it doesn’t ‘crowd out’ anything.
In the case where an antibody attaches but doesn’t actually “inactivate” the virus due to a mutation, that’s because the virus’ attack surfaces are still present and exposed (otherwise, it would be inactivated.) Again, we wouldn’t expect to see “crowding out” of other antibodies.
And lastly, there’s the extremely unlikely scenario of sufficient mutation that existing antibodies give us Vaccine Enhanced Disease. This is both something vaccine designers explicitly focus on to minimize the risk of, and would require an extreme amount of change to enable.
That makes sense; I was wondering about this exact thing. It seems like VB is painting a worst-case scenario where a bunch of things go wrong in a specific way. Perhaps not impossible, but based on what you’re saying, there’s no reason to be unusually concerned.