Class switch towards non-inflammatory IgG4 antibodies after vaccination

https://www.science.org/doi/10.1126/sciimmunol.ade2798

by SQL2219 • 4 years ago

51 31 4 years ago

I found this paper to be less than objective in its introduction and commentary. Statements were made that had nothing to do with the research itself, and therefore did not relate to supporting data and were superfluous. I really don’t like reading papers like this because my initial reaction is always “why do they say this, and who reviewed the paper that allowed them to pass?”

kuhewa• 4 years ago

E.g.?

phtrivier4• 4 years ago

ELI5 : what does it mean in practice for vaccine and booster schedules ? Are we heading towards "no less than one booster every year" ? Or the contrary ? Would it change the frequency / severity of side effects with successive boosters ?

Basically, is it "good" news, "bad" news, or just, news ?

(To clarify in case that's what caused the downvotes : I'm not writing "bad" news because I think vaccines are "bad". If we really need to get boosted once a year, so be it - but it would arguably be a worse outcome than "not needing it")

ergonaught• 4 years ago

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."

bitL• 4 years ago

"Since Fc-mediated effector function could be critical for viral clearance, an increase in IgG4 subclasses might result in longer viral persistence in case of infection."

phtrivier4• 4 years ago

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 of "more sick people" is, well, "bad" news ? Again, maybe there is a silver lining here, and I don't know enough about the topic.

Or maybe it's just a "Burn After Reading" thing.

"I guess we learned not to do it again" ? (except, no, we'll have to do it again, and FSM knows what would have happened if...)

[1] https://youtu.be/SlA9hmrC8DU

michaelrpeskin3• 4 years ago

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 mucosal membranes when you breathe in something foreign. In the context of COVID, we'd expect to find IgM antibodies in people exposed to the virus because the mucosal membranes of the respiratory systems are the first places exposed to a respiratory virus.

2) IgG3 - this is created in your blood and is the main killer of a foreign object. This is what you think of when your immune system is fighting a virus. It also drives the inflammation which is what you generally recognize as the "flu-like symptoms".

3) IgG4 - this is created in response to what we recognize as allergens. For example, if you breathe in a bunch of pollen in the spring, you may have an IgG3 response and feel terrible. Or you body may recognize that that foreign object really isn't a big deal. In this case it will create IgG4 which basically tells your body to ignore the object until it's cleared. It's kind of the opposite of IgG3: rather than ramping up inflammation to fight the object, it's ramps it down and just says "nothing to see here" so you don't waste resources fighting something harmless.

What they found is that vaxxed and boosted people have a ton of IgG4 floating around and little to no IgM and IgG3.

So what does that mean? Here's where people are going to get spun up because we have to create hypotheses and test them. But even stating some hypotheses will cause the political machine to get mad.

1) IgM is really good at stopping viruses early. From this we'd expect that unvaxxed people exposed to COVID to be more resistant to future infections because the first exposure will create IgM and the virus will be stopped/attenuated in the nose. I don't know the state of the research on this, but it's a hypothesis to test.

2) IgG4 is a bad thing in the context of a replicating virus. If you have IgG4, it's telling your body to ignore the virus because it's "just an allergen". That's fine for pollen which will be cleared out of your system, but it's bad for a replicating virus because it can replicate unfettered. The hypothesis to test here is if people who are more vaxxed have more (re)infections of COVID. Another thought is that the infection may never go away and flare up occasionally (long COVID?). Again, I don't know the research, we need to test these hypotheses to understand it.

But it is one piece of the puzzle and a plausible explanation for this (https://www.medrxiv.org/content/10.1101/2022.12.17.22283625v...) where we see a nearly linear increase in vaccine doses and COVID infection. Again, these are just hypotheses and we need to test them without getting political about the vaccine.

This may also be a plausible explanation for COVID related OAS (Original Antigenic Sin) and ADE (Antibody Dependent Enhancement) that some researchers claim they see.

At a minimum we can say that the more vaxxed and boosted a person is, the more "non-standard" (compared to other vaccines) their immune response is, and that's worth further investigation.

bzmrgonz• 4 years ago

Very thorough ELI5, thank you. I wonder how difficult/expensive it is to test for IgG4? I ask because I do routine 7 day water fast every 3 months, and in theory, the body is suppose to repair and expel foreign substances. More importantly, it is also suppose to renew the immune system. I'd like to test the amount of IgG4 in my body.

phtrivier4• 4 years ago

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 causing the reinfections ?

At this point, I'm looking forward for someone saying "it's more complicated than that", which is not a great sign :/

sterlind• 4 years ago

thanks for the explanation. I'm really curious though, how do we know this is unique to the mRNA vaccines, or covid vaccines in general? could infection with SARS-CoV-2 in unvaccinated people also lead to IgG4 production?

Like, the mRNA vaccines are basically doing the first few steps of what the real virus does: attaching to ACE2 receptors with Spike and producing viral proteins from mRNA. It's hard for me to see where the immune system could get led down a different path.

carry_bit• 4 years ago

To the degree it's news, it's not "good" news, but further research is needed to see just how "bad" it is.

The concern here is if the worse-case scenario turns out to be true: that the mRNA-based vaccines, and especially the boosters, end up training the immune system to tolerate the infection rather than clear it. That would mean a significant fraction of the population are at risk of outcomes ranging from persistent COVID to death, and becoming breeding grounds for more variants in the process.

Hopefully further research rules out that scenario.

henearkr2• 4 years ago

Fwiw non-inflammatory antibodies could still incapacitate the virii when they attach to their spikes, if they are enough concentrated in the blood.

So, what about it? Is this effect powerful enough to be helpful?

arde2• 4 years ago

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 such a mutation because all those people get infected and shed the virus while being mostly asymptomatic or experiencing mild symptoms. New strains should soon appear if this is correct, and some other dire predictions are made in that case (see Geert Vanden Bossche).

henearkr2• 4 years ago

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 again mRNA vaccines etc) could also apply to any other receptor, couldn't they?

amluto3• 4 years ago

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 get two doses of the chickenpox vaccine don’t get chickenpox [0].

With the Covid vaccines, for some reason public health authorities are okay with flying blind. The effect of, say, bivalent boosters on their recipients’ blood neutralizing viruses and virus-like imitation viruses are studied in the lab (but even the studies of this effect by the vaccine makers are barely public and seem to consist mostly of press releases). Studies on actual infections rates seem to be almost completely absent.

And now we have this study, which at least gives a plausible mechanism by which repeated mRNA vaccination could fail to improve actual immunity or maybe even reduce it.

What we need is a real study of whether vaccine recipients on different schedules get sick and how sick. And these need to be well designed, ongoing, and public.

For what it’s worth, IgG4 production is observed in allergy patients receiving immunotherapy, which consists essentially of very frequent repeated vaccination against allergens.

[0] The chickenpox vaccine is incredibly effective against chickenpox — it makes any of the Covid vaccines look pathetic. But, to be fair, the effect of chickenpox vaccination on shingles seems to only slowly coming in to focus by real studies. But to give the FDA credit, figuring this out takes multi-decade studies.

tinus_hn• 4 years ago

With the Covid vaccines, for some reason public health authorities are okay with flying blind.

The worst part is with politicians who are okay with forcing the general public to trust the sight of these blind public health authorities.

bjtitus• 4 years ago

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...

amluto3• 4 years ago

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

orbifold2• 4 years ago

Ok, well then it might turn out that some of the fringe scientists were right all along. A healthy young male like me would probably have been far better off to not receive any kind of vaccine, I only got Covid after a third booster and I don’t think I could have had it any worse.

amluto3• 4 years ago

A healthy young male like me would probably have been far better off to not receive any kind of vaccine

If you mean “might” instead of “would probably”, then maybe I’d agree that you’re on the right track.

I don’t think I could have had it any worse.

You’re alive and you haven’t described severe disability lasting at least a year, so this part is just not correct.

Being healthy and young reduces the risk of severe outcomes, but not to zero.

orbifold2• 4 years ago

It’s all hypothetical at this point, I reluctantly followed the guidance, more or less because I didn’t want to be inconvenienced too much. You are right I could have suffered worse, but then again I have absolutely no risk factors and statistically my chance of death or serious outcome was very close to zero regardless of vaccine status.

There was a clear indication from the data in Israel that nothing was working as it was advertised in Europe. Now high profile publications are coming out that confirm some of the worst fears, so who knows maybe at some point these people will have to take some accountability.

hoc• 4 years ago

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 case if an infection not seeming life-threatening to your body, a softening of the overall reaction might actually just be the right path to persue. The question is whether we want that in this case or whether we want to further move that towards a more protective optimum in the future with these insights.

For the "I knew it" and "we should have waited" discussion, I personally prefer an early protection, even with a lower reaction, that still keeps me from being hospitalized over being nakedly exposed like we were in the early days of that pandemic. We might have forgotten about this with the current "mild" Omicron variant.

I would love to see the study include severe breakthrough infections, if there are any, to see if the dampening effect and antibody distribution would be different in these cases.

anon291• 4 years ago

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

busymom03• 4 years ago

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.

Class switch towards non-inflammatory IgG4 antibodies after vaccination

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