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Comment by bvaldivielso | Hacker News Reader

As far as I understand (I don't have any background in biology), mutations will happen regardless of whether people are vaccinated or not. There might be mutations that make the virus circumvent some vaccine protections, but those mutations would take place even if we weren't vaccinating people. Nothing about the vaccines "guides" the virus towards specific mutations. Mutations are random. If this is correct, why would not vaccinating people be better than vaccinating them? (In fact, the fewer people that get infected, the less room for the virus to mutate).

Is my understanding correct? Can anybody point out where I'm wrong?

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Mutations are random, but the factors that result in a mutation leading to improved reproductive success are not. An organisms environment helps select for beneficial mutations.

I get that. I just don't see why an environment where half the people are vaccinated would lead to worse outcomes, even if mutations take place that can bypass the vaccine's protections.

derbOac explains it here:

https://news.ycombinator.com/item?id=27822773

It's not so much that vaccination is iatrogenic, it's that when you have a sizable percent vaccinated, but a sizable percent not, you're kind of in this worst of all possible worlds from an evolutionary standpoint.

If worldwide vaccination rates were very high, it would drive viral transmission down to negligible levels and effectively slow the rate of evolution by decreasing the viral population size to something very small.

If there were no vaccine, we'd be back where we were, but there would be no vaccine to evolve against as a selection pressure.

When you have, say, 50% vaccination, you have a sizable population to evolve in, and the vaccine as a pressure selecting random mutations.

If the vaccine is very effective in preventing asymptomatic transmission as well as symptomatic infection, it might not be such an issue. This might be why the delta variant seems to not be doing much in vaccinated individuals. But it seems vaccinated individuals do still transmit the virus asymptomatically at some nonnegligble rate, and then you have a sizable nonvaccinated population.

What I'm worried about now isn't so much the current state of the delta variant, it's where things are headed. Specifically, how this evolves in (1) the unvaccinated populations, and (2) what the future might hold for vaccine resistance in the future.

It's one reason I'm sort of angry with the FDA for playing this power game about approving a booster vaccine. It's not their job to evaluate the need for the booster, it's their job to evaluate the safety and efficacy of it. By the time they change their minds about need, it might be too late.

> It's not so much that vaccination is iatrogenic, it's that when you have a sizable percent vaccinated, but a sizable percent not, you're kind of in this worst of all possible worlds from an evolutionary standpoint.

How is this any different from natural immunity? The immunity conferred by vaccines won't put any more selective pressure for escape mutations than natural immunity would. And the only alternative here is for no one to get vaccinated, and therefore letting the virus run rampant through the population indefinitely. You aren't wrong about a sizeable portion of the population not being immunized quick enough may possibly result in escape mutations. But the only possible alternative fixes none of those issues, while also leaving the entirety of the public at risk.

You might be right about natural immunity as an alternative. I think implicitly the idea is there's something incomplete about the vaccine antigen (however it gets presented) that might create a bigger "possibility surface" for mutations to develop that would retain the core functions of the virus but allow the virus to escape detection. As opposed to naturally acquired immunity, where your body has been exposed to the entire thing (but then has been exposed to the functional virus).

Let's say I tell you to look for a suspect. You say "ok, what do they look like?" In one case, I show you a picture of their face. In another case, I introduce you to them and let you inspect them completely and take whatever photos or do whatever 3d scanning you want. It's probably easier for the suspect to develop a disguise in the former case than the latter? Maybe not, but I think that's the general idea.

It is interesting to think about resistance evolution in the context of the specific vaccines that are available vs natural immunity. I seem to recall reading that the choice of viral components to target in the vaccines was done in part so as to leave little wiggle room for mutations, so you might be right about evolution of resistance relative to natural exposure. But theory and reality are always different.

FWIW, I'm not trying to imply people shouldn't get vaccinated, or that vaccines are somehow causing problems. There's just reasons to think that if vaccination rates aren't high enough, it's easier for the vaccines to become ineffective over time than if almost everyone were vaccinated.

It depends if the vaccine is sterilizing (destroys the virus) or leaky (symptoms are prevented but virus is not destroyed).

Leaky vaccines do change evolutionary pressure and increase the likelihood of escape variants.

For a case study in the worst case outcomes of leaky vaccines, see Marek's disease [1].

It seems like the mRNA vaccines are at least partially leaky, so there have been concerns raised and alarms sounded by researchers.

[1] https://en.wikipedia.org/wiki/Marek%27s_disease

If the argument is "we shouldn't use vaccines because of escape variants" then I don't see why we should fear escape variants more than we do any other kind of variants.

If the argument is "we should build up a big inventory of vaccines and infrastructure to deploy them to the population in a very short timespan" then I see some logic to that but it's not at all obvious that the math works out.

You are correct. Mutations are random. The only even remotely valid point made by those fearing vaccination effects is that vaccines may cause selective pressure where the random mutatations that escape vaccine-induced immunity become more dominant. But even that point doesn't mean vaccines shouldn't be employed because

1. The same selective pressure exists for natural immunity 2. The implication is that we shouldn't get vaccines, because we may get variants that get around our vaccines. This is like asking the fire department not to put our a raging house fire because it might cause water damage to the home.

Its also worth noting that none of the major variants observed so far came about after vaccines began being used on the population at large, and the above point about selective pressure at vaccine immunity is only an issue when large swaths of people aren't getting vaccinated, allowing the virus a large number of "shots on goal" to mutate in a way that eventually provides escape capabilities.

There is absolutely no logic to these arguments about vaccines causing mutations.

As far as I understand, and I don't understand much. Also I am not endorsing vanden Bossche because I don't understand much. Furthermore, just as everyone else, he is just trying to sell his vaccine over others'.

The issue is selective pressure. Yes, the virus will mutate. But under an mRNA vaccine, only the spike protein needs to mutate for the vaccine to be render useless. In other words: mutating the spike protein will give the virus access to very broad unimmunized population.

Up to that it makes perfect sense to me and my limited evolutionary knowledge. I can't tell wether is right or wrong. But it makes sense.

He goes further saying that antibodies from vaccines are more affine to the virus, even with mutated spike protein, this compromises the natural immune system, given it will try to fight off infection with useless vaccine-learnt antibodies rather than with natural antibodies. This will make the virus more deadly.

This seems off to me. I can't see the logic, but I will be happy to be corrected. How can something be ignored by the virus and be more affine to it?

Again, he says that all these issues are solved with his vaccine, once he finishes it.

> The issue is selective pressure. Yes, the virus will mutate. But under an mRNA vaccine, only the spike protein needs to mutate for the vaccine to be render useless. In other words: mutating the spike protein will give the virus access to very broad unimmunized population.

> Up to that it makes perfect sense to me and my limited evolutionary knowledge. I can't tell wether is right or wrong. But it makes sense.

The issue with this is that the spike protein has to mutate enough for vaccine induced immunity to fail to recognize it, but the spike protein is critical for the virus actually entering and infecting cells, and therefore there isn't a whole lot of mutating it can do while remaining functional.

On the other hand, there is some evidence that vaccines targeting more than just the spike protein (as well as natural immunity) may potentially be more at risk for the "antigenic sin" trap, in which the immune system fails to respond to mutated versions of a virus as well as it does to the original version it encountered.

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