I’ll try to avoid repeating what we already addressed in the previous two articles on this subject. After mRNA vaccination the immune response against Spike is shifting to IgG4, which is how your body responds after repeat exposure to stuff it needs to tolerate, like bee venom, pollen or peanut proteins.
First the big chart, of what you want to see after a SARS-COV-2 infection:
Left you see who does the neutralization, right you see what percentage of total antibodies they are. Despite being just 3% of your antibody mass, IgG3 is carrying out 42.2% of the neutralization.
IgA is busy in mucus dealing with this virus, IgM responds to the infection by bringing the viral load down, IgG3 then joins the fight and tags any remaining hide-outs this virus has, so that your body doesn’t end up tolerating this nasty sarbecovirus in the background.
If it wasn’t obvious yet, for whatever reason our bodies do seem to be tolerating the spread of this virus through our population. Look at what’s happening to my poor little country:
Levels of this virus in sewage are back to record heights. Clearly the population isn’t learning to force this virus into the background.
The death toll is rising in unison with the viral load, because the excess mortality is not a direct product of the vaccine, it is an indirect product of the vaccine interfering with our response to this virus:
We have a big wave of deaths in march 2020, then we had two deadly winters, so excess mortality is now supposed to be negative. We already “ran out” of the people who would die during the flu season. Yet 27% more people died than you would expect last week. That’s supposed to worry people with an IQ above room temperature, but they just call it “unexplained” and try to ignore it.
I point this out to you, because I’ve been arguing on Twitter with one of the authors of the study we’re going to look at, who insists that his findings, which fit the other teams whose findings I reported on in the past two posts are “unexpected”, but “nothing to worry about”. I honestly somewhat doubt he genuinely believes this. I want to explain here why the findings are worrying, so let’s start by looking at their findings and what is actually new.
You already know the story: After the second shot, IgG4 begins to show up. This gets worse with the breakthrough infections, then it gets worse again with the third shot. Now we have updated findings from breakthrough infections after the third shot. And this will shock you, but it gets worse again:
On average, the four who had a breakthrough infection after their booster are now at 42.45% IgG4. The cohort as a whole is at 19.27%, up from just 0.04%, so the ones who haven’t had a breakthrough infection yet will end up at a similar position: A response that is entirely IgG4 dominated.
The one useful new thing these guys and gals did was to ask the obvious question: Is this normal for other pathogens we’re commonly exposed to? So they looked at another virus, the virus causing misery for a lot of kids right now, RSV. They saw we don’t respond to RSV with an IgG4 response:
Nobody showed this response to RSV and it’s not even really seen after constant tetanus vaccination.
You just don’t want to see an IgG4 response to a respiratory infection. Out of the IgG’s, it’s mainly IgG3 and some IgG1 you want to see. One of the authors claims that it doesn’t matter that they’re switching to IgG4, because the antibodies don’t just matter for triggering phagocytosis (your immune cells eating the virus particles), they also matter for neutralization.
This is nice and well, but you run into two problems:
- The virus evolves. It rapidly evolves to avoid the most neutralizing antibodies. Neutralizing potential against XBB and BQ.1 is basically gone.
- IgG4 isn’t really meant for neutralization. Out of the IgG’s, IgG3 is the excellent virus neutralizer. What IgG3 does in the case of SARS2, is that they have their tails bind together. This means that out of all the four subclasses, IgG3 is showing 50-fold stronger neutralization than the other three subclasses against SARS2.
And now it’s time to drink, because have a look at what happens to IgG3 after three shots:
There is some IgG3 left in some people after the second shot, but by the time they get the third shot, they’re all universally down to a flat zero.
If you’re wondering how we end up with these fancy graphs:
It probably has something to do with us ridding our bodies of the most competent IgG antibody against this virus, replacing it with one we use to tolerate stuff like pollen, peanut proteins or bee venom.
This has never happened before. There are now the known unknowns, like whether the body ends up tolerating persisting infections due to this completely IgG4 dominated response, along with the unknown unknowns, questions we should be asking ourselves that most people haven’t even realized we need to be asking ourselves.
Here’s the big question I run into: So your experiment failed, you created an IgG4 dominant antibody response in soon to be billions of people. The IgG4 antibody response is homogeneous, it’s the same epitopes that everyone is learning now to tolerate.
Are you ready for this one?
What does it mean for other viruses?
That’s the big painful question. If you told me everyone has a different immune response to different regions of Spike, but everyone now deploys IgG4 antibodies to those regions, that would be bad enough for our relationship to SARS-COV-2.
But bear with me, as I pull up this old chart again:
You see the unvaccinated immune response in A at the bottom. You see that it’s pretty different in everyone.
You see the immune response of the vaccinated at the top. You see it’s rather similar in everyone, with distinct regions that receive the strongest response.
For some of those regions the virus doesn’t mind our antibody response, so those regions tend to stay the same. In other regions the antibody response is interfering, so the virus mutates to change those regions. This means that after a while, the IgG response is recalled for a shrinking subset of these regions, so you get a strong IgG4 response for a handful of epitopes, BUT THOSE EPITOPES ARE THE SAME FOR BASICALLY EVERYONE!
What I’m trying to say, is that there are now certain non-self amino acid chains that billions of human beings around the world are suddenly learning to tolerate. RNA respiratory viruses all work with pretty similar building blocks.
Some of these amino acid chains that we now tolerate in the case of SARS2, are chains that also show up in other respiratory viruses. And there will be respiratory viruses, that don’t have those chains yet, but can mutate themselves, to incorporate them in positions where they now currently have to deal with potent IgG3 antibodies.
In other words: A homogeneous population-wide shift towards IgG4 for certain antibodies, can end up impacting our relationship to respiratory viruses other than SARS2 as well. You could expect for example, that vaccinated people may become better asymptomatic spreaders of other respiratory viruses, like RSV. We see evidence of cross-reactive antibodies between SARS2 and the human corona viruses. Do you want those to switch from IgG3 to IgG4? Probably not.
It seems a plausible hypothesis worth investigating to me, that the massive surge in RSV that Western nations are seeing, is a consequence of vaccinated adults now beginning to tolerate RSV, thus leading to a jump in infections in children, as they’re exposed to it more often. With children now getting these infections from vaccinated adults rather than from other children, the infectious dose they receive will tend to be higher. This could be sufficient to explain the higher virulence observed in children.
Immune damage in children from SARS2 infection is also a hypothesis worth investigating of course, but asymptomatic spread from adults is also possible.
You have to keep in mind: The complete IgG4 shift only happens after breakthrough infections after the booster shot. In other words, the non-SARS2 viruses have not had much time yet, to evolve to adjust to the brave new world we now live in, where everyone is stuck with a strange subset of IgG4 antibodies for certain epitopes.
The IgG antibodies mainly bind to regions about 5 to 6 amino acids long, although it varies quite a lot. If some other virus like RSV, Influenza or the human corona viruses has such a region, it may find itself very happy! One of those nasty IgG3 antibodies that made its life miserable is gone, now replaced with an IgG4 antibody that is not capable of binding its tail to the other IgG4 antibodies for enhanced neutralization.
And if it doesn’t have such a region yet, but it could eventually get there after swapping one amino acid for another, then in due time you may find yourself wondering why you now suddenly have a big influenza problem, or a big RSV problem, or a big problem with some other pathogen.
Again, I’m sorry that I didn’t fully understand this two years ago. I understood it rather basically. I understood the big important principle: You can’t go out and homogenize the population’s immune response to a respiratory virus, this is profoundly dangerous.
Look back at what I wrote long ago:
One of the factors required for our species to reach such high population densities as we have reached today is the diversity of our immune response from person to person.
If we had HLA genes with very little diversity, we would all have a very similar immune response to pathogens. The lack of diversity in their HLA genes is one of the factors that made Native Americans so vulnerable to the viruses introduced by European colonizers: These viruses could spread in an environment of a homogeneous immune response, which allowed these viruses to evolve to make optimal use of that particular environment.
If we had HLA genes with little diversity, pathogens would evolve variants that overcome that particular immune response. The diversity of our immune response prohibits this from happening: Any particular change can’t help a pathogen much, when everyone responds to the pathogen in a different way.
With the spike based vaccines, we have done the exact worst thing you could possibly do: We homogenized the human immune response, to a new virus that is rapidly becoming more genetically diverse.
It’s again just this same basic principle I outlined here above, but this time we’re zooming in on this class switch to IgG4. I wouldn’t be worried about the impact on other pathogens if we had some switch to IgG4 that differs from person to person. But everyone now has select amino acid combinations that don’t occur in our own body (that is, peptides that we would normally not tolerate and chase down with antibodies if they show up in our blood), that everyone is now learning to tolerate!
We intervened in something that we just don’t properly understand, at the scale of billions of people.
Allow me to give you an anecdote. Long ago, in the 19th century, a Swedish man named Arrhenius, related to an autistic Swedish girl you might have heard of, realized that we were changing the atmosphere. People thought this was pretty nice, as they assumed it would happen slowly. Eventually most people forgot about it again.
By the 60’s we realized we were now emitting quite a lot of this strange gas, it was changing the atmosphere. Again the experts were not worried. “The ocean will probably deal with it” was the consensus among very smart people, WHOSE SPECIALTY IT WAS TO STUDY THIS SORT OF STUFF. It was only really in the 1980’s, that basically everyone agreed we were dealing with a real problem.
In this context, I want you to have a look at the scientist who announced his findings on Twitter:
I’m an anonymous Dutch college dropout with a predilection for obscure psychedelics, he is a virologist with a Phd. I’d perfectly understand if you wish to believe him over me, that’s the response most people seem to have.
But what I see, is a scientist saying “eh, the ocean will deal with it”.
He is a virologist and things are not going well in the field of viruses. We have too many people dying. We have a sarbecovirus that is not going away. The hospitals around the Western world can’t deal with the burden of sick people anymore.
And most important of all: The children are getting sick.
Maybe you don’t want to endow billions of people with a similar looking IgG4 antibody repertoire targeted at an RNA respiratory virus. Maybe all sorts of respiratory viruses and other pathogens can use that as an opportunity.
You committed an unprecedented experiment with billions of people, our immune systems are now responding in an unprecedented manner to a respiratory pathogen and we now see unprecedented numbers of people sick from respiratory infections.
If you are a virologist, I think you’re supposed to be worried right now.
Update 1: A critique you might have of my warning, that a shift towards IgG4 may impact other respiratory pathogens too, is that cross-reactivity of antibodies may not be sufficient.
And yet, we already know there must be substantial cross-reactivity between SARS2 and a number of other RNA respiratory viruses, for a simple reason: Subunit influenza vaccines (ie not live vaccines) showed a clear 89% reduction in risk of a severe SARS-COV-2 infection.
If influenza antibodies impact SARS2, SARS2 antibodies impact influenza. And if SARS2 antibodies are shifting towards tolerance, that will impact influenza. The impact will merely get more relevant over time, as these other viruses adjust through mutation and natural selection to benefit optimally from this shift towards IgG4.