Looking for reasoned discussion on Geert Vanden Bossche's ideas?

post by megabranflake · 2021-06-06T17:07:20.987Z · LW · GW · 15 comments

This is a question post.

Considering the current covid hysiteria and censorship on social media platforms I'm finding it hard to find reasoned discussion of Geert Vanden Bossche's ideas. They seem to be centered around vaccine immune escape and original antigenic sin. If you have anything to contribute please do. Thanks

Answers

answer by Dentin · 2021-06-06T18:51:25.312Z · LW(p) · GW(p)

The core issues I had with it are that the scenario he's envisioning just isn't playing out in the real world.  He has a mostly coherent model he's working with, and he's making the valid claim that "for some set of parameters and constants, terrible things happen!"  It's just that in real life, the parameters and constants are nowhere near what's needed for the badness he's claiming.

Specifically:

  • His scenario requires a much higher mutation rate than we're seeing;
  • His scenario assumes vaccine immunity isn't very strong, but what we're seeing is incredibly strong immune responses;
  • His scenario assumes that natural immunity (from being infected) is significantly stronger than the vaccine generated immunity, which doesn't appear to be the case.

Basically, none of his assumptions are valid, and so his final prediction is for a reality that isn't ours.

answer by Lukas_Gloor · 2021-06-06T19:46:19.696Z · LW(p) · GW(p)

I found this video interesting and quite concerning. 

Vanden Bossche makes two arguments: 

(1) The ongoing mass-vaccination campaigns are poorly timed. We started vaccinating right about when lots of concerning new variants were showing up independently in different locations, suggesting that SARS-Cov-2 is quick at evolving. The vaccines are targeting outdated variants, and some vaccines are already only partly efficient. This creates the perfect conditions for further viral evolution. Therefore, we should expect immune escape really soon. Booster shots may help temporarily, but that's not a good solution because you're always a step behind, and if the outbreak isn't under control at any point, you just keep pressuring the virus to evolve and you thereby make it better at evading antibodies.

(2) There are two types of antibodies: 'innate immunity,' which is based on undiscriminating antibodies, and acquired immunity, which you get from the vaccines (or from having had the virus previously). Innate immunity is why young people do very well against the virus. Now, when you give people specific antibodies from the vaccines, those antibodies will still bind to the virus, but they won't neutralize it. They will be useless, but they'll crowd out the less discriminating antibodies from innate immunity, the ones that would actually work against the virus. This way, vaccinations could end up harmful. 

My impression is that his points in (1) seem undoubtedly accurate and pretty scary, but I think it's plausible that update vaccine shots will be made and distributed quickly enough to at least keep things under control (similar to Influenza each year). Besides, I don't see a good alternative. (Given that trying to eradicate the virus globally requires an unrealistic degree of willingness and coordination abilities.) 

I lack the expertise to judge his arguments in point (2), but there's something at 1:08:20 in the video that Vanden Bossche says that makes me think his mind is ideologically clouded. He talks about 'natural immunity' in this hyped way and suggests that 80%-85% of people "don't get any symptoms." I think that's just false. Asymptomatic infection is <50% with Covid. So given that his entire argument rests on understanding innate immunity, and given that he gets a central fact about it wrong in a way that suits his biases, makes me think he may not be right about these concerns. 

Of course, people can be wrong about some details and still be right about the general picture. I do think the mechanism he proposes sounds at least plausible to my lay ears. In particular, I think the situation "mass vaccination campaign during a global pandemic against a fast-mutating virus" is quite unprecedented, so it's not crazy to think that policy makers may not be thinking about virus evolution and immunity mechanisms in fine enough detail to realize that they're creating a dangerous mix of circumstances. 

One thing I'm skeptical about: If his concern with working antibodies being crowded out were correct, wouldn't we see instances where anti-flu vaccines end up harming people, because they'd also crowd out antibodies from innate immunity? But this is basically never the case, no? If you gave an outdated flu vaccine to a young person, they wouldn't do worse against the current flu virus, would they? That's another reason why I I'm skeptical, but I don't understanding anything about the specifics of the immune system.

Similarly, what about previous infection? If someone got infected by the original Covid variant in 2020 and then reinfected with some future evolved Covid variant that's very good at evading previous antibodies, it seems like Vanden Bossche's model would predict that they're going to do worse than if they had never had a previous Covid variant. Would we actually see that in reality? So far, antibodies seem to always be good to have. 

comment by Lukas_Gloor · 2021-06-06T21:21:35.730Z · LW(p) · GW(p)

At 1:40:22, he claims that we see young people without risk factors getting severe Covid for basically the first time only now, because they get infected in the time window right after vaccination when their antibodies are immature and only serve to crowd out innate antibodies. 

That claim sounds dubious to me! Firstly, there's always been a (small) risk for young people to develop severe Covid. The way both he and Weinstein talk about "young people are already immune" seems a bit dumb to me. Secondly, if getting infected right after vaccination increases a young person's risk, that would show up in the data. But no one is talking about this yet. Am I missing something? 

comment by Dentin · 2021-06-06T20:22:54.607Z · LW(p) · GW(p)

#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.

Replies from: ChristianKl, Lukas_Gloor
comment by ChristianKl · 2021-06-06T21:01:33.146Z · LW(p) · GW(p)

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. 

comment by Lukas_Gloor · 2021-06-06T20:49:04.361Z · LW(p) · GW(p)

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.) 

Replies from: SDM
comment by SDM · 2021-06-06T21:23:02.920Z · LW(p) · GW(p)

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.

Replies from: Lukas_Gloor
comment by Lukas_Gloor · 2021-06-06T21:51:45.141Z · LW(p) · GW(p)

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.

Replies from: Dentin
comment by Dentin · 2021-06-06T23:33:21.889Z · LW(p) · GW(p)

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.

Replies from: Lukas_Gloor
comment by Lukas_Gloor · 2021-06-06T23:57:37.066Z · LW(p) · GW(p)

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. 

comment by ChristianKl · 2021-06-06T19:57:29.504Z · LW(p) · GW(p)

Booster shots may help temporarily, but that's not a good solution because you're always a step behind

mRNA technology would give you a turn around of two weeks from identifiying a new strain and vaccinating people against it if we could convince our governments that COVID-19 is a problem that not only requires lockdowns but also serious actions. 

While we are talking about vaccinating against new strains, RadVac currently has room for funding and if you think that you will want to vaccinate yourself against new strains this fall and the government doesn't change their policies RadVac does give you a fast way to vaccinate. Them having done as much research before that point might be important (and thus a good donation target at this point in time).

Replies from: gbear605, stuart-anderson
comment by gbear605 · 2021-06-07T00:47:44.172Z · LW(p) · GW(p)

Note also that the FDA has already approved that shots for alternate strains would be able to have much more limited testing, just for safety, which would take about two months. Slower than ideal, but given that production and distribution takes a while anyway, it's not too bad, and (judging by the response to the current vaccines) the additional testing will be important for getting people to actually take the vaccine.

 

Two months behind isn't great, but it's short enough that I'm not worried.

comment by Stuart Anderson (stuart-anderson) · 2021-06-07T04:11:22.337Z · LW(p) · GW(p)

-

Replies from: ChristianKl
comment by ChristianKl · 2021-06-07T10:38:05.577Z · LW(p) · GW(p)

If this was truly an emergency 

What does truly mean? The word points to the No true Scotsman-fallacy. Why would highly political governments which structures that don't lend themselves to truth finding have a better idea about whether it's truly an emergency then we do? 

Where does your belief in governments being very competent come from?

Replies from: stuart-anderson

15 comments

Comments sorted by top scores.