#1 is where I would hinge a lot of objection. Specifically:
“The vaccines are targeting outdated variants, and some vaccines are already only partly efficient. This creates the perfect conditions for further viral evolution.”
Yes, the vaccines are targeting outdated variants, and yes, the vaccines are only partially efficient. But the mRNA vaccines, even partially efficient, are still hugely overkill. From previous posts here on LW, even partially effective mRNA vaccines likely cut transmission by a factor of 100 between the reduced infection rate and reduced infectiousness when infected.
On the other hand, “perfect conditions for viral evolution” require a much, much weaker vaccine response, one that barely keeps up with the spread of the virus. For maximum evolutionary pressure, you’d want a continuous rate of infection, with a spreading factor very near 1.0, so even slight changes in the virus can be strongly selected for. And it just so happens that this is exactly what we were doing prior to vaccine rollout.
Of course, even the mRNA vaccines aren’t a guarantee that we’ll eradicate the virus. There’s a handful of marginally effective vaccines out there (Sinovac anyone?) which will be much easier for mutations to overcome, and there’s areas which will be infection hotbeds for years, and there’s antivax communities which will likely be infection centers forever. But by broadly rolling out strong vaccines, there’s every reason to believe that the ‘nightmare scenario’ of Bossche will be less likely, not more.
There’s a handful of marginally effective vaccines out there (Sinovac anyone?) which will be much easier for mutations to overcome
When it comes to Sinovac it’s worth noting that given that it’s a inactivated-virus vaccine it creates different selection pressure then all the spike protein vaccines.
And it just so happens that this is exactly what we were doing prior to vaccine rollout.
I agree, if all of this was only about argument (1), then it’s clear that the ongoing mass vaccinations are best.
But Vanden Bossche wants us to look at both arguments together, (1) and (2). His point is that having the antibodies from an outdated vaccine will soon be bad for you, because the types of antibodies set off by the vaccine will “get in the way” of innate antibodies.
Are you specifically saying that it takes too long for viral evolution to escape vaccine-generated antibodies so much that they go from “suboptimally useful” to “actually harmful because they get in the way?” I think that’s plausible based on the observation that every vaccine in circulation so far is overwhelmingly net positive to have, and we’ve already vaccinated 50%+ of the population (at least in some fortunate countries) and could continue “keeping up” with booster shots. So all of that makes sense and makes me feel reassured.
However, I wonder if we’re maybe underestimating the selection pressure from “virus evolves in unvaccinated population” and “virus evolves in population vaccinated by an outdated vaccine.” The Delta variant evolved in India where only few people were vaccinated. Somewhere there (or in the vicinity, e.g. Nepal), it apparently acquired a mutation that’s been studied in the Beta variant, which gives the virus better immune escape. This looks like somewhat fast virus evolution already, and the selective pressures will get even stronger. The UK has the Delta+ (“Nepal”) variant already, and is reopening the economy. The selection pressure will strongly favor mutations that make the vaccine-generated antibodies less useful. Vanden Bossche is saying that the antibodies are targeted at the virus in a fragile way, so that once you dial up the selection pressure for vaccine escape, it could happen quickly. Therefore, I worry that the argument “virus evolution has been too slow so far” is not watertight because the selection pressure for the specific thing that he’s most worried about (vaccine-generated antibodies becoming a hinderance soon enough) is going to be much stronger in the near future than it ever was. Did you consider all of that in your assessment?
(Even if it’s true that selection pressure will increase, it seems like Vanden Bossche can’t be confident that the increase will be strong enough. So what he describes is only a possibility that depends on parameters of virus evolution.)
According to this article (https://www.deplatformdisease.com/blog/addressing-geert-vanden-bossches-claims) - the key claim of (2), that natural antibodies are superior to vaccine antibodies and permanently replaced by them, is just wrong (‘absolute unvarnished nonsense’ was the quote). One or the other is right, and we just need someone who actually knows immunology to tell us
Principally, antibodies against SARS-CoV-2 could be of value if they are neutralizing. Bossche presents no evidence to support that natural IgM is neutralizing (rather than just binding) SARS-CoV-2.
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.
#1 is where I would hinge a lot of objection. Specifically:
“The vaccines are targeting outdated variants, and some vaccines are already only partly efficient. This creates the perfect conditions for further viral evolution.”
Yes, the vaccines are targeting outdated variants, and yes, the vaccines are only partially efficient. But the mRNA vaccines, even partially efficient, are still hugely overkill. From previous posts here on LW, even partially effective mRNA vaccines likely cut transmission by a factor of 100 between the reduced infection rate and reduced infectiousness when infected.
On the other hand, “perfect conditions for viral evolution” require a much, much weaker vaccine response, one that barely keeps up with the spread of the virus. For maximum evolutionary pressure, you’d want a continuous rate of infection, with a spreading factor very near 1.0, so even slight changes in the virus can be strongly selected for. And it just so happens that this is exactly what we were doing prior to vaccine rollout.
Of course, even the mRNA vaccines aren’t a guarantee that we’ll eradicate the virus. There’s a handful of marginally effective vaccines out there (Sinovac anyone?) which will be much easier for mutations to overcome, and there’s areas which will be infection hotbeds for years, and there’s antivax communities which will likely be infection centers forever. But by broadly rolling out strong vaccines, there’s every reason to believe that the ‘nightmare scenario’ of Bossche will be less likely, not more.
When it comes to Sinovac it’s worth noting that given that it’s a inactivated-virus vaccine it creates different selection pressure then all the spike protein vaccines.
I agree, if all of this was only about argument (1), then it’s clear that the ongoing mass vaccinations are best.
But Vanden Bossche wants us to look at both arguments together, (1) and (2). His point is that having the antibodies from an outdated vaccine will soon be bad for you, because the types of antibodies set off by the vaccine will “get in the way” of innate antibodies.
Are you specifically saying that it takes too long for viral evolution to escape vaccine-generated antibodies so much that they go from “suboptimally useful” to “actually harmful because they get in the way?” I think that’s plausible based on the observation that every vaccine in circulation so far is overwhelmingly net positive to have, and we’ve already vaccinated 50%+ of the population (at least in some fortunate countries) and could continue “keeping up” with booster shots. So all of that makes sense and makes me feel reassured.
However, I wonder if we’re maybe underestimating the selection pressure from “virus evolves in unvaccinated population” and “virus evolves in population vaccinated by an outdated vaccine.” The Delta variant evolved in India where only few people were vaccinated. Somewhere there (or in the vicinity, e.g. Nepal), it apparently acquired a mutation that’s been studied in the Beta variant, which gives the virus better immune escape. This looks like somewhat fast virus evolution already, and the selective pressures will get even stronger. The UK has the Delta+ (“Nepal”) variant already, and is reopening the economy. The selection pressure will strongly favor mutations that make the vaccine-generated antibodies less useful. Vanden Bossche is saying that the antibodies are targeted at the virus in a fragile way, so that once you dial up the selection pressure for vaccine escape, it could happen quickly. Therefore, I worry that the argument “virus evolution has been too slow so far” is not watertight because the selection pressure for the specific thing that he’s most worried about (vaccine-generated antibodies becoming a hinderance soon enough) is going to be much stronger in the near future than it ever was. Did you consider all of that in your assessment?
(Even if it’s true that selection pressure will increase, it seems like Vanden Bossche can’t be confident that the increase will be strong enough. So what he describes is only a possibility that depends on parameters of virus evolution.)
According to this article (https://www.deplatformdisease.com/blog/addressing-geert-vanden-bossches-claims) - the key claim of (2), that natural antibodies are superior to vaccine antibodies and permanently replaced by them, is just wrong (‘absolute unvarnished nonsense’ was the quote). One or the other is right, and we just need someone who actually knows immunology to tell us
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.
Do you still need proof that natural antibodies are superior to the Spike-focused vaccine-induced antibodies ?
There you go: https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1
https://www.nature.com/articles/s41586-021-03944-y
The article you cited is not science, it is a Bolshevik-style hit piece.