Class switch towards non-inflammatory IgG4 antibodies after vaccination • Hacker News Board

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#21

Post by michaelrpeskin » Tue, Dec 27, 2022, 5:16 PM UTC

phtrivier wrote: post #16

michaelrpeskin wrote: post #8

Earlier quoted context omitted.

Here's my ELI5 attempt. Disclaimer: the immune system is very complex, even experts really don't understand it as much as we think we do. This is a very simplified view of the system, but I think captures a very large fraction of the story. Let's focus on three types of antibodies - the things your immune system creates in response to a foreign object in your body - for this story: 1) IgM - this is created in your mu…

Thanks for the explanation. Although, as I understand it, I do not see how it can be anything else than a worst case scenario ? When someone inevitably spins it as "they sold you vaccines that will let you catch the disease _more_ often, we told you so, subscribe to my podcast / buy my book / vote for me / etc...", what is the counterargument ? That we need more data to confirm ? That there can be other factors causi…

There may have been nefarious intentions, and a lot of smart people I follow go that way. But I'm still more charitable than just about everyone I know. I call it the "entropy of ignorance". When dealing with a novel rapidly spreading pathogen that we have no experience with, there are more ways to make a wrong decision than a right decision. A wrong decision then opens up more choices where another wrong decision can be made. A purely statistical argument would show that we'd get the outcome wrong.

In non-emergency cases, we have some random people that follow the right path and that message gets amplified and we find a solution. In this case, that didn't happen (or maybe I should say "hasn't yet happened"). We are seeing with the latest twitter files that some people who were more right then wrong were silenced. The bias towards a more right answer was taken away. Why were they silenced? Could be something as simple a trying to make an easy message "anything that promotes vaccine hesitancy is bad" because good people truly believed that the vaccine would get out of it and they didn't want any confusion.

Back to your comment about "worst case scenario." Yes this is bad, if the vaccine (and in particular the boosters) are actually destroying the immune system, we have a problem. Typically we would have tested this for a long time to see this effect (which is not unknown in the immunology community) but for some reason "we didn't have the time" and we rushed it into millions (billions?) of people. That is bad. Can it get worse? Yes! What if the latent IgG4-enabled virus evolves in vaccinated people and we get another outbreak of a worse virus?

You can probably imagine more bad scenarios. I was a co-author on a paper about significant more (1000x) pregnancy and fertility adverse events after the COVID vaccine compared to the flu vaccine. So we're talking generational effects!

Anyway, not to be too doom and gloom here, but I think you're right "it's more complicated than that" and "we need more data" we just need to collect everything we can, make hypotheses, test them, and learn. That requires lots of open communication.

Extra info: earlier this summer I started to put together a figure to illustrate the "entropy of ignorance" It's outdated, I've learned more since then, but this was my best understanding this summer. You can see how it's easy to have a bad decision keep compounding into more bad decisions. And they can easily happen randomly, it doesn't take nefarious reasons.

https://imgur.com/YZKu3Wn

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#22

Post by anon291 » Tue, Dec 27, 2022, 5:44 PM UTC

hoc wrote: post #19

Before everybody from the more esoteric communities chines in with some new reason why we all should immunize "naturally", let's not oversee that breakthrough infections were triggering the same effect. Also, in general you don't want your immune system to be more aggressive/destructive than necessary when you consider having to rebuild tissue afterwards, which also might include more risks the older you get. In the…

Why is naturally in quotes? Do you deny the immune system exists? I'm vaxxed, but this sort of conspiratorial writing and discourse coming from the vaccine pushers is harmful to science and flies in the face of reality. The immune system exists. The human immune system is capable of learning

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#23

Post by phtrivier » Tue, Dec 27, 2022, 6:05 PM UTC

michaelrpeskin wrote: post #21

phtrivier wrote: post #16

Earlier quoted context omitted.

Thanks for the explanation. Although, as I understand it, I do not see how it can be anything else than a worst case scenario ? When someone inevitably spins it as "they sold you vaccines that will let you catch the disease _more_ often, we told you so, subscribe to my podcast / buy my book / vote for me / etc...", what is the counterargument ? That we need more data to confirm ? That there can be other factors causi…

There may have been nefarious intentions, and a lot of smart people I follow go that way. But I'm still more charitable than just about everyone I know. I call it the "entropy of ignorance". When dealing with a novel rapidly spreading pathogen that we have no experience with, there are more ways to make a wrong decision than a right decision. A wrong decision then opens up more choices where another wrong decision ca…

> Typically we would have tested this for a long time to see this effect (which is not unknown in the immunology community) but for some reason "we didn't have the time" and we rushed it into millions (billions?) of people

Well, in all fairness, the "some reason"s were thousands people dying _every day_ in western countries, overloading health systems. Anyone playing the "let's wait two more years, just to be sure" card had a _very_ hard sell.

To follow your analogy, this is probably a situation where there is vastly more wrong decisions to make, and the right ones require the benefits of 20/20 insight, which, well, GPT-42, maybe ?

To roughly quote a former PM from that period: "my job these days is to arbitrage between bad decisions".

This is were the scientific method of searching for the truth clashes with the politics of managing a human society. Not a particularly new debate, I suppose...

For "laughs" : I almost wish we'd go the complete opposite road next time, keeping the vaxxes in the lab as long a possible, just to see the opposition parties everywhere spread conspiracy theories about the "secret vaccine that the government does not want you to take", etc... Just, for a change.

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#24

Post by adamredwoods » Tue, Dec 27, 2022, 7:24 PM UTC

michaelrpeskin wrote: post #21

phtrivier wrote: post #16

Earlier quoted context omitted.

Thanks for the explanation. Although, as I understand it, I do not see how it can be anything else than a worst case scenario ? When someone inevitably spins it as "they sold you vaccines that will let you catch the disease _more_ often, we told you so, subscribe to my podcast / buy my book / vote for me / etc...", what is the counterargument ? That we need more data to confirm ? That there can be other factors causi…

There may have been nefarious intentions, and a lot of smart people I follow go that way. But I'm still more charitable than just about everyone I know. I call it the "entropy of ignorance". When dealing with a novel rapidly spreading pathogen that we have no experience with, there are more ways to make a wrong decision than a right decision. A wrong decision then opens up more choices where another wrong decision ca…

>> Extra info: earlier this summer I started to put together a figure to illustrate the "entropy of ignorance"

Wow, that's heavily biased. "Create a culture of fear and weakness -> Enforce useless mask-mandates"? That's extremely biased (and ignorant in itself).

Also, it does not follow potential ramifications of some major decision, for example, "lockdown -> no" ends there, failing to illustrate outcomes when observing current spread rates, mutation rates, and death rates of a virus.

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#25

Post by bjtitus » Tue, Dec 27, 2022, 7:38 PM UTC

amluto wrote: post #11

IMO, this illustrates a major problem with the current approach to Covid vaccine research. With most vaccines on the market, the effect of vaccination according to the recommended schedule is tested for real: actual disease outcomes are studied and the vaccine schedule is determined accordingly. For example, people who get both measles vaccine doses largely don’t get measles (and largely is quantified). People who ge…

> Studies on actual infections rates seem to be almost completely absent.

Numerous studies have been presented to ACIP over the last few years covering asymptomatic infections, symptomatic infections, and hospitalizations. From the 2021 meeting covering Pfizer-BioNTech, there were 5, [1] 17 [2], and 13 [3] of these studies, respectively. There are similar sets for Moderna [4]. From what I've seen of the ACIP meetings, those are the results they focused on the most.

I don't have much knowledge of medical research but I don't see how this could possibly be "completely absent". Would love to hear more about what's missing from these and the dozens of other studies which have been done since.

1: https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-pfizer...

2: https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-pfizer...

3: https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-pfizer...

4: https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-pfizer...

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#26

Post by arde » Tue, Dec 27, 2022, 8:33 PM UTC

henearkr wrote: post #20

arde wrote: post #17

Earlier quoted context omitted.

Some argue that precisely that mechanism generates evolutionary pressure for the virus to mutate so as to avoid being attached to by the antibodies but still being able to enter the cell (maybe through a different receptor, and there exist some viable candidates for this). The fact that such a large population has been vaccinated with mRNA vaccines, it is thought, has created a huge reservoir for the virus to attempt…

Interesting, however the emergence of new strains would happen anyway and is not tied to the validity of this hypothesis (thus you could not e.g. use the appearance of new strains as a confirmation of it). But did you mean "strains that are not using the spike protein anymore to enter cells"? In which case, why do you think it would be harder to tackle than the original virus? In my opinion, the same work (developing…

It's the spike protein that would mutate so as not to be attached by antibodies, but it would still attach to cell receptors (probably different ones).

Yes, new mRNA vaccines could be produced and distributed, thereby generating even more tolerance as this article shows and making things even worse for people's immune systems if so. The point is these vaccines are generating resistance to the virus but at the same time, unlike traditional ones, they are making the immune systems tolerant of the virus. The infection is incompletely suppressed, symptoms are mild or imperceptible, but the virus is getting passed on despite being partly suppressed.

The emergence of new strains is favored when there is a large medium (the reservoir population of people, tolerant but infected and shedding) where the virus can proliferate (thus plenty of viral code copying, where mutations happen) and where there is selective pressure (i.e., an advantage to the new strain such as being able to enter cells even more effectively because of the lack of interference compared to the current strain) for a mutated virus to thrive.

It would be harder to tackle because it would be even more infective than the current strain (given the tolerance that has been introduced in the population) but at the same time more aggressive (because more cells being entered would mean more damage to the body) and maybe with different kinds of damage (because it could trigger autoimmune responses, they say, although I'm not sure how that argument goes).

I'm not an expert on this so I cannot elaborate further, but that's the idea as far as I grasp it. We'll see, I guess.

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#27

Post by amluto » Tue, Dec 27, 2022, 8:34 PM UTC

bjtitus wrote: post #25

amluto wrote: post #11

IMO, this illustrates a major problem with the current approach to Covid vaccine research. With most vaccines on the market, the effect of vaccination according to the recommended schedule is tested for real: actual disease outcomes are studied and the vaccine schedule is determined accordingly. For example, people who get both measles vaccine doses largely don’t get measles (and largely is quantified). People who ge…

> Studies on actual infections rates seem to be almost completely absent. Numerous studies have been presented to ACIP over the last few years covering asymptomatic infections, symptomatic infections, and hospitalizations. From the 2021 meeting covering Pfizer-BioNTech, there were 5, [1] 17 [2], and 13 [3] of these studies, respectively. There are similar sets for Moderna [4]. From what I've seen of the ACIP meetings…

All that is great but out of date. For the bivalent booster, we have:

https://www.cdc.gov/vaccines/acip/recs/grade/covid-19-bivale...

Which seems to be entirely lacking in efficacy data. MMWR just has immunogenicity and speculation, too:

https://www.cdc.gov/mmwr/volumes/71/wr/mm7145a2.htm

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#28

Post by busymom0 » Wed, Dec 28, 2022, 3:21 AM UTC

phtrivier wrote: post #18

ergonaught wrote: post #4

Earlier quoted context omitted.

It isn't news. It's science. "Further investigations are needed to clarify the precise immunological mechanisms driving this response and to evaluate whether an IgG4-driven antibody response affects subsequent viral infections and booster vaccinations. This is not only relevant for potential future vaccine campaigns against SARS-CoV-2, but also for new mRNA-based vaccine developments against other pathogens."

Well, it's science because it's the result from a study published in a respected peer reviewed journal. However, it's also "news", because the hypothesis that getting boosted could make you _more_ sick is pretty, well, say, novel. (Hypothesis still to be confirmed, I get it, but if I understand the other comments correctly,that's the jist of it ?) Also, in médecine, pretty much anything that goes into the direction o…

The flu shots have shown a similar problem during the 2009 pandemic which was first thought to be happening only in Canada but was later on confirmed in other countries too and also confirmed in ferrets

> "seasonal flu vaccination almost doubled the risk of infection with pandemic flu":

https://www.cbc.ca/news/health/flu-vaccine-paradox-adds-to-p...

> "Canadian researchers noticed in the early weeks of the pandemic that people who got a flu shot for the 2008-2009 winter seemed to be more likely to get infected with the pandemic virus than people who hadn't received a flu shot."

> The ferrets in the vaccine group became significantly sicker than the other animals, though all recovered. "The findings that we show are consistent with the increased risk that we saw in the human studies," Ms. Skowronski said.

https://www.theglobeandmail.com/life/health-and-fitness/heal...

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#29

Post by busymom0 » Wed, Dec 28, 2022, 5:40 AM UTC

phtrivier wrote: post #23

michaelrpeskin wrote: post #21

Earlier quoted context omitted.

There may have been nefarious intentions, and a lot of smart people I follow go that way. But I'm still more charitable than just about everyone I know. I call it the "entropy of ignorance". When dealing with a novel rapidly spreading pathogen that we have no experience with, there are more ways to make a wrong decision than a right decision. A wrong decision then opens up more choices where another wrong decision ca…

> Typically we would have tested this for a long time to see this effect (which is not unknown in the immunology community) but for some reason "we didn't have the time" and we rushed it into millions (billions?) of people Well, in all fairness, the "some reason"s were thousands people dying _every day_ in western countries, overloading health systems. Anyone playing the "let's wait two more years, just to be sure" c…

I think an objective look at the data clearly showed that the people dying or getting hospitalized were either elderly or had comorbidities. So vaccinating the 60 or 65+, obese, and those with comorbidities should have been enough while doing long term testing for the rest. Instead, we got mandates.

Re: Class switch towards non-inflammatory IgG4 antibodies after vaccination

#30

Post by busymom0 » Wed, Dec 28, 2022, 5:43 AM UTC

hoc wrote: post #19

Before everybody from the more esoteric communities chines in with some new reason why we all should immunize "naturally", let's not oversee that breakthrough infections were triggering the same effect. Also, in general you don't want your immune system to be more aggressive/destructive than necessary when you consider having to rebuild tissue afterwards, which also might include more risks the older you get. In the…

> let's not oversee that breakthrough infections were triggering the same effect

Source? And why are the non-mRNA vax not showing this effect?

> that still keeps me from being hospitalized over being nakedly exposed like we were in the early days of that pandemic

Unless you were elderly (over 60 or 65) or have comorbidities, it should have at least been a choice to take it or not take it. Instead we got mandates and sold the dream of the vax ending the pandemic.