In a r/askscience , there was a report that they are also working on a surface identifying vaccine, which doesn’t mutate (as much?), instead based on the spike protein. They didn’t earlier because it takes a longer time to develop and is harder.

vaccines don't "mutate" ?? Are you saying they're developing more broadband vaccine that can handle more mutation by the virus?

Not OP, but I think what was meant is identifying a vaccine that targets proteins(s) on the surface of the virus rather than only the little "spikes" that protrude from it. Early vaccine development latched onto the idea that the spike proteins are critical to the virus' ability to infect humans, so mutations would likely/hopefully/maybe make the virus less dangerous to humans anyway.

But, it would be ideal if we could also find proteins on the surface of virus that are less likely to mutate (than other proteins in the virus) that we could teach our immune systems to look for.

It sounds like you might be a good person to review and give your thoughts on this interview between Bret Weinstein, an evolutionary biologist, and Geert Vanden Bossche, a virologist, who discuss this in length and detail it for layperson? https://www.youtube.com/watch?v=BNyAovuUxro

Skimmed it, seems like its a lot of bullshit wrapped up in plausible sounding science.

The H1N1 pandemic is an interesting historical model, and the more deadly later waves indicate that more virulent variants were produced in that pandemic as well. He seems to be arguing that vaccines are causing the variants and that natural herd immunity is better, which is bullshit.

First of all the vaccines are 80-90% effective, even against variants, which greatly reduces the number of people that the vaccine can use to mutate new variants. When there are vaccination failures the vaccines prevent symptoms, prevent viral load and shedding and transmissibility. That cuts down on the production of variants as well.

There's also considerable cross protection in the human immune system since immunity isn't binary like an on/off switch. As a historical example the people born before 1957 were exposed to H1N1 and had cross reactive T-cells to the 2009 H1N1 pandemic. So after mutating in pigs for 50 years the human immune system still recognized the H1 envelope protein sufficiently to take the edge off of that pandemic to make it essentially nothing. And we vaccinated younger people (with I.M. flu vaccines) and didn't see the emergence of hugely virulent H1N1 variants.

The variants are arising now because there's a decreasing fraction of the population which is 100% susceptible to infection and the virus is chasing after that decreasing fraction by increasing transmissibility, viral load and virulence. The vaccines will be effective at taking people out of that 100% susceptible pool even though they're not absolutely perfect. The virus will eventually run out of that 100% susceptible pool and will have to start optimizing for costly immune escape variants which will lower its virulence in order to try to get around vaccinated and recovered individuals immune systems.

This right now, with the evolution of more virulent variants is the WORST time to be playing the natural herd immunity card. Everyone needs to get vaccinated to protect themselves and to put the virus under more pressure to make costlier mutations than it has been able to make so far. Spreading this idea that the vaccines are producing the more lethal variants is literally going to get people killed by having them skip vaccinations and wind up contracting one of the most lethal variants the pandemic is likely to produce. That is optimizing for the worst possible roll of the dice for yourself.

So yeah, he should be banned off of social media and you're killing people by spreading this misinformation.

Cheers.

The COVID-19 vaccine is less effective against the variants, and arguably unknown if immunity developed from dead-virus based vaccines would provide higher effectiveness against variants and reduce potential for escape.

You're arguing to ban critical thinkers having a conversation, perhaps instead you should be ban off social media for wanting to censor intellectuals/critical thinkers?

Especially since you're seemingly giving a well-thought out response but you immediately admit you skimmed it, and then wrongly claim they're pushing for herd immunity.

You also reference cross immunity, however those weren't using mRNA vaccines afaik, and so the mechanism and spread that the immunity will cover for variants won't be the same.

I was wrong, you're not as rational or thorough of a person I thought you might be based on your initial explanation that I responded to.

If mutations are random events, how does a virus know it is under more pressure because randomizing events occur less often?

> the more it'll have to make those costly evolutionary choices and become less virulent

Why would evolution select for less virulence in a virus like this? Given covid doesn't rely on symptoms to spread like the common cold seems to, it would seem like the evolutionary pressure would be the opposite. Rather than moderate symptoms, instead jack up viral loads in the host as quickly as possible to spread before the immune system gets involved.

/not a biologist

That is what it is doing right now.

But it is doing that in response to evolutionary pressure because when a good fraction of the people are recovered or vaccinated then an R0 of 3.0 doesn't work as well when its chasing after those remaining susceptible people.

There'll be an upper limit to how much it can increase its binding to ACE / viral load / R0 though. Once you hit that point infections should fall off a cliff. Then the virus will start to come under pressure to achieve immune escape.

To really achieve immune escape the virus should have to make costly mutations. It shouldn't be able to pick the most optimized spike conformation, it'll have to pick a spike conformation that immune systems don't recognize.

It can't be ruled out that the virus has so much "room" to mutate on the spike protein that high virulence total escape mutants could be formed, but probably not. There are estimated to be 20 epitopes on the spike that the immune system recognizes and to really escape it needs to mutate sufficient to change all of them. Some of them are likely to be expensive to the virus. And if we get booster shots like I said to box it in more, then it should run out of room and start to mutate more towards stealth and less towards virulence.

And there's historical parallels to 1918. At first the H1N1 virus came back in waves that became more virulent. Then once more than half the world had been infected it started to come back as seasonal influenza and spread endemically in humans until 1957. Some of that is likely partial immunity from previously infected individuals, some of that is probably that the virus stated to favor evolving to escape detection and not for virulence and transmissibility.

There's physical limitations on what it can do, basically.

Every mutation runs the risk of reducing its binding affinity to ACE receptors to get inside cells - or might impede cell entry functions.

Given the amount of infection out there, whatever "easy" mutations might've been available to it clearly haven't been very useful in increasing its rate of spread - and haven't touched anything the vaccines target.

So it's quite likely that whatever needs to happen to evade the vaccines is otherwise deleterious to its virulence.

I’m curious, what is your education background in?

Do you have some sort of medical education or this is a regurgitation of some sources you’ve read as a hobbyist?

I ask this because you seem to talk from a place of authority and fact and i respect that but typically thought of Ycomb as a place comp sci folks usually congregate.

Maybe you should ask for sources instead. Authority is the wrong thing to trust in science

However, isn't this how Bayesian thinking works? You give a higher prior to your believe depending of the source.

That's why we ask for sources. If one doesn't trust lamontcg to know what they're talking about, we shouldn't trust them to be honest about that fact. We're often more likely to have Bayesian priors about a primary source than the people who refer to them.

Yes, but in this case authority would be your prior, and a source would be the data to update that prior. If you are only relying on authority, you are solely going off of your personal biases, which while potentially informative, isn't as useful as actual data.

A perfectly reasonable approach; but then it is easier to ask people you trust rather than reading HN. Anonymous internet people are inherently unreliable.

Authority is constantly used as an effective source of trust in science.

As an effective shortcut but it's still the wrong thing, ultimately, to trust.

A scientist who doesn’t use sources effectively and accurately themselves is not to be trusted as either an authority or as a scientist. It is the greatest sin for a researcher.

What is the alternative? Everyone grabs postdoctorate degrees in everything that might come up?

Your question shows why it is a shortcut.

Heuristic might be a better term.

There is also a massive reproducibility crisis in science, and the two points are not not unrelated.

The “reproducibility crisis” is largely overblown. Individual scientific papers have always been close to junk on average. Look at a wide swath of papers from say the 1950’s or even 1850’s and you see not just poor methods but also outright fraud.

It absolutely isn't overblown, and "individual scientific papers have always been close to junk on average" is a pretty damning indictment.

Meta-studies have found that, depending on the field, up to 70% of published papers can't be reproduced. I'm not sure its possible for considering that a crisis to ever be "overblown".

Even 30% of papers being reproducible is orders of magnitude better than random chance. That’s the signal that pushes science forward.

As to old papers, go back to the 1950’s and plate tectonics was still being debated. What do you think the other geological papers where based on? When you read a specific older paper it’s generally because it stood the test fo time, but that’s just selection bias.

I completely agree... in principle. That being said, I actually think we tend to underestimate the value of trusting experts. Often times the sources out there that one could be quoting espouse conflicting and ambiguous conclusions and it ironically takes an expert to be able to parse through them all. If we could all trust experts a bit more and, rather than ask for sources, instead ask our experts to explain their reasoning to us, I think we'd all be better off in the long run in that we'd actually be learning from them rather than trying to constantly bootstrap becoming experts ourselves.

Unless you have a background in immunology the sources are probably not terrible useful to you.

Probably, but not definitely. The only thing preventing you from understanding the sources yourself is some effort. It's not as hard as it is sometimes imagined.

One problem with that is that any individual study should be read in the context of other published literature, if you want to form an informed opinion. The only alternative is authority - either looking at the journal where it was published, the authority of the authors, or the authority of someone who recommended the paper.

Otherwise, it's easy to find plausible-sounding papers that have failed to reproduce in subsequent studies, that use too low samples compared to similar studies with different conclusions, that were later retracted etc.

Oh, they will be, but in the opposite way to what GP seems to want. That is, I'd look at the sources as further sources of authority :). E.g. a bunch of papers from multiple teams, with some published by high-profile journals or authored by well-known researchers, indicates it's relatively safe to trust their conclusions. A bunch of papers from the same few people who seem to want to push their pet theory indicates low trustworthiness and need for independent verification.

Unless you've studied the domain in question in depth, it's not like you could use the citations in any other way. Trust, as a heuristic, is fundamental to advanced research as much as it is for everything else in society.

They could be useful to somebody else, and that's a good enough reason to have them.

I've been reading HN for over a decade and I've seen comments from people with a huge variety of backgrounds. Many people switch fields later in life or they might just be interested in technology/startups.

> or this is a regurgitation of some sources you’ve read as a hobbyist

I'm sure it's not your intention, but this phrase might be mistaken for an offensive, negative critique of the OP's abilities, which may make the OP hesitate to respond, or respond defensively.

If you are purely seeking information, without prejudice, then your question would be more effective if you ended it before the 'or'.

I’ve no knowledge regarding that commenter, but there are large amounts of diverse experts in various fields on here. It’s one of the reasons I like it so much here

>but there are large amounts of diverse experts in various fields on here.

Yeah, and they mostly keep their mouths shut except to confirm what everyone is already saying because trying to correct the narrative or dispel a popularly held belief on a site with a voting mechanism is an exercise in futility. Nobody will read your comment when it's dead so why bother.

I'm sure plenty of people here enable showdead. I do at least.

HN has tons of users with training in bio and medicine, including a surprising number of practicing physicians and academics. This is a big community. People's mental image of it tends to be much smaller and less diverse than it actually is. It's a lot more than "comp sci" folks, which is good, because it's not supposed to be limited that way.