Always an interesting and at times amusing readSomething wickedthis way comes (and by something, I mean mRNA immune system dysregulation)
Why the paper reporting an explosion in IgG4antibodies after the mRNA boosters is so unsettling - in a hopefully easy tounderstand Q+A
Jan 2
Hope youenjoyed the last week of 2022… and now back to business.
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Time for astory in Q+A format. Why?
By now,you have probably heard about the Science Immunology paper showing that people who have received mRNA Covid vaccines produce more of an unusual antibody called IgG4 over time. A number of mRNA skeptics, including me, wrote about it last week.
But thereasons why the paper is so troubling may still not be clear. So here’s a (withluck) digestible explanation, starting with what is probably the most importantquestion: what’s the worst-case scenario?
1: What’s the worst-case scenario?
Glad youasked.
Theworst-case scenario: the mRNA shots lead to a doom loop, robbing vaccinatedpeople of a crucial immune system tool against the coronavirus in a way thatworsens with each newinfection.
Thus, overtime, the average severity of Covid infections will increase. People will takelonger to get better once they’re infected. Hospitalizations and deaths willrise. The health-care system will come under worsening strain.
Oh, andsome people may suffer nasty autoimmune side effects too, includingpancreatitis, kidney disease, and even aneurysms.
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2: Is that all?
Not quite.The truly worst-case scenario would come if those changes combine with a new,more dangerous Sars-Cov-2 variant that our weakened immune systems cannotclear.
3: Seriously? How likely is all that?
Yes,seriously.
Howlikely? No one knows. The good news is that we are probably relatively safefrom a more dangerous variant as long as Omicron subvariants predominate. SinceOmicron first appeared in late 2021, it has gone through many mutations butremained less dangerous than the original or Delta variants.
As for the“doom loop?” It is probably not very likely, but does “not very” mean 3 percent chance? 20 percent ? 40 percent? Anyone who claims to know is lying. We know much less about the immune system than we pretend, and even less about how these specific changes might affect people in the long run.
As theresearchers who found this anomaly noted, it has not yet been proven to cause worse disease in the people it affects. But it hasn’t been disproven either. Researchers simply have not looked at real-world outcomes in enough people who have these changes to know.
4: So what are the changes again?
Our immunesystems make antibodies against “antigens,” invaders like the coronavirus.Those antibodies attach to the antigens and play two crucial roles - they“neutralize” them by keeping them out of our cells, and they recruit otherparts of the immune system to destroy them.
Vaccinationslike the mRNA shots accelerate this process by pre-exposing people to theantigen, so that our bodies know how to respond to it before they are infected. The mRNA shots do so by causing our cells to make a part of the coronavirus called the spike protein. They are very effective at making us make spike proteins. In response, our immune systems make very high levels of anti-spike protein antibodies.
5: That’s good, right?
Well, yesand no. We clear those vaccine-generated antibodies much more quickly than“natural” antibodies we make in response to infection. This fact became clearwithin months of the original two-dose vaccination series. Thus the push forboosters, which (briefly) cause another rise in antibodies.
But the Science Immunology paper showed something else, something unusual and unexpected. People who have received mRNA shots make more of an antibody called IgG4, which doesn’t try very hard to destroy the invaders. That process accelerates sharply in people who have received a booster, a third shot.
Itaccelerates further in people who are infected after being jabbed. Thus the potential doom loop, leaving vaccinated people with only these IgG4 antibodies.
6: And then they would totallyunprotected from the coronavirus?
No. IgG4scould still offer some protection through their ability to “neutralize” theSars-Cov-2 viral particles - preventing them from entering our cells andreplicating. (Unlike bacteria, viruses cannot reproduce on their own - theyneed our own cellular machinery to do so.)
Theproblem is that the Omicron coronavirus spike has a different shape than thespikes of earlier coronavirus variants. The anti-spike protein antibodies wegenerate - either after infection or vaccination - already have a harder time neutralizing it.
So wecould be facing a double whammy; our immune systems would have antibodies thatwould still attach to the virus, but they would do a bad job both destroying itand keeping it from entering our cells.
7: That sounds bad.
It is. Wewould still have protection through our T-cells, which form a final line ofdefense. But other research has shown that T-cells don’t match up as wellagainst Omicron as against earlier variants, though they lose their potency relatively slowly compared toantibodies. Research has also shown that additional boosting doesn’t help the T-cell response.
8: So if boosters don’t help T-cells, andthey cause this IgG4 issue, and the antibodies disappear in a matter of months,and they don’t work very well against Omicron anyway, we have absolutely no reasonto give anyone more mRNA shots?
Bingo.Correct. Yes. (Except for vaccine company profits.)
At thispoint, the long- and medium-term downsides clearly outweigh whatever short-termincrease in antibodies boosters provide.
9: So what can vaccinated people do, ifmore shots are off the table?
Mask up!
I jest. Atthis point, vaccinated people do not have any real options to stop the IgG4process. However, being infected with Sars-Cov-2 could provide some protection-
10: I thought you said that was part ofthe doom loop?
Hold on!
- byhelping the immune system create antibodies to another part of the virus called the nucleocapsid. These anti-nucleocapsid antibodies will not stop future infections, but they may help stop severe disease. (Yes, more infections might both help and hurt. The immune system is tricky.)
11: Do you have any good news?
Since thepaper came out, certain aggressive anti-vaccine writers have offered horrifyingscenarios, for example claiming the IgG4 changes might hurt our ability to fightthe flu and other viruses. Those theories are vanishingly unlikely. But thereal issues are plenty serious.
12: But this is all speculative, right?
Yes.Except that it explains the growing divergence between the countries that usedmRNA and those that did not in the last few months. China aside, the mRNAcountries have performed far worse than the the rest of the world since early 2022. The mRNA countries have had huge numbers of Covid infections and reinfections that seem divorced from any seasonality. Covid hospitalizations and deaths have been relatively low, but those are now rising too. And overall excess mortality has been stubbornly high.
13: So scientists and health authoritiesand the vaccine companies are now going to launch an all-hands investigation tofigure out how serious this finding might be?
You’refunny.
14: Seriously -
Seriouslyhas anything in the last two years suggested such an investigation is coming?
15: Right. Okay. Speaking of thecompanies, shouldn’t they have known about this IgG4 stuff?
Yes. Thisfinding is vitally important, and should have become part of the discussionaround boosters more than a year ago.
16: Did they? Did they say anything?
Did they?It’s not clear. They certainly didn’t say anything publicly (as far as I cantell). Did they privately tell regulators? Probably not, because even the mostindustry-captured regulatory agency would have had to make this informationpublic.
17: What now?
Hopefullysome independent and honest academics will investigate both the changes thatare occurring on the cellular level and how they may be impacting people’sresponse to the virus. And we all wait and hope that the ugly trends thatcountries like Japan - which is very highly mRNA vaccinated and just had itsworst month for coronavirus deaths since the epidemic began - do not continue.
18:Wait? That’s the best yougot? Wait?
Not waiting - wantingmedicine at Warp Speed - is what got us into this mess to begin with
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