IF YOU ONLY HAVE TIME TO READ ONE POST I POSTED TODAY, READ THIS ONE.
You don't have to understand all the science (I surely don't), but keep reading past what you don't understand so you get the general picture. Radagast is reaching the same conclusion Geert reaches, although I'm not sure if their way to get to that conclusion is the same because the science is over my head and I don't have the patience to try to figure it out like I used to do with Geert (I don't try anymore with him either, I realized after hours listening and figuring out the science after a lot of concentration that it doesn't matter if I follow it all to get the gist of what they're saying). It's worth reading even if we don't understand all of the nitty gritty. I would love if Phillip McMillan would interview both of them together and get a discussion going! (and break it down so we can all understand all of it)
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(fair use applies)
Hey look, serotypes!
Radagast
April 16, 2024
I have to point this out. About half a year ago, I said that
you’re probably going to end up with SARS2 serotypes, simply because it was unlikely by now that something new that emerges would be superior enough to completely eradicate the XBB lineages. Immunity would first be reoriented against the new serotype and that would then create a landscape within which the old serotype could re-emerge.
Well guess what happened. It turns out there’s an
XBB lineage with a weird insertion at 212 that emerged in Canada and spread around the globe. So now you have two versions of the virus, both with insertions in different parts of the NTD. They’re both going to be under pressure to change the NTD in different ways. For JN.1 it’s straightforward to start deleting stuff around the first loop, due to the insertion at 16. We
see it happening in multiple JN.1 lineages, a deletion at 31, just after the first immunogenic loop and a bit after the insertion, that allows a new glycan to be added at 30. But this XBB variant would have more of an incentive to delete chunks further along in the NTD.
Remember, it’s when deletions and new glycans emerge in the NTD, that the last antibodies that neutralize the virus in most of the population are going to fail. You will end up with very fusogenic variants, that spread by moving from one cell into another, without ever being in reach of the antibodies. The antibody response against the RBD is already pretty much useless by now.
The important thing to keep in mind is that once you have multiple of these highly fusogenic serotypes circulating in the population, you can’t vaccinate anymore. Most of the population already has high concentrations of antibodies, vaccination under these conditions won’t improve the population’s protection, it will merely favor one serotype at the cost of the other. By now it’s clear that the BA.2.86* Spike doesn’t do a clean sweep: It
stays stuck around 93%, so it doesn’t completely wipe out the other lineages.
There are probably other serotypes out there too, we just don’t see them because sequencing is down by 99%. There’s a
weird one in France, but nobody knows how widespread it is. There’s also a
derivative of the original Omicron still circulating in Nebraska, infecting multiple people.
I know you’ve probably seen it argued there will be some sudden new doomsday variant this summer that leads to overnight vaccine failure. I don’t think this is likely, although it is inherently impossible to rule out.
In the coming weeks we can expect S:R346T, S:F456L, S:S31del to grow globally dominant.
Right now, adding the whole thing together suggests
a 117% growth advantage.
What seems far more likely to me unfortunately, is that we’re gradually going to see different serotypes emerge: XBB lineages and BA.2.86 lineages, along with lineages based on whatever else is still out there.
Those lineages will undergo deletions in the immunogenic loops of the N-Terminal Domain, facilitated by the rare insertions they tend to develop in the NTD. These deletions will increase fusogenicity and thereby increase the intrinsic virulence of the virus.
That ultimately results in a virus that behaves more like the original SARS.
The reason this is happening
So why did this happen? Well, allow me to show you something.
There is a notable difference by now between vaccinated and unvaccinated people, in regards to the regions their T cell receptors look for. This has been studied, in people who were infected in the first half of 2022.
Among the unvaccinated, they found
strong overrepresentation of the S673-699 epitope. On the other hand, among the vaccinated, they found strong overrepresentation of these four regions:
S135-177, S264-276, S319-350, and S448-472.
The first of these four is easy to understand: It’s the N3 loop of the NTD. The other three regions are also in the NTD, but don’t correspond neatly to any of the known immunogenic loops.
But here’s the whole picture, which tells the story in my opinion:
I would argue it’s pretty obvious what’s going on here. The unvaccinated adaptive immune response tends to focus on regions in S2. The vaccinated adaptive immune response tends to focus on the N-Terminal Domain. We also see it strongly preferentially focuses on the region around 180, which is
an infection enhancing site. The N5 loop also seems to be preferred.
So it seems straightforward, to expect that the NTD is going to undergo radical changes now, now that antibodies against the RBD have become useless. As the loops in the NTD grow shorter, by deletion mutations, you end up with a virus that behaves more like SARS1.
The
entire Spike protein is covered by glycans, with the exception of the receptor binding domain. But now that the RBD evades the antibodies, we’re reaching the point where the antibody response depends on those last few regions of the NTD not covered by glycans, where antibodies can still bind to neutralize viral particles.
You also have to keep in mind: As more and more of the Spike protein becomes inaccessible to the T-cells, whether due to evolution to resemble our own proteins, deletions, steric hindrance, or glycans that are added, you’re going to see people’s lungs populated by an increasingly homogeneous population of T-cells.
With every breakthrough infection, the immunological abnormalities further escalate. That’s why you now see a very different antibody response against JN.1, when comparing vaccinated and unvaccinated people, as the vaccinated keep recalling antibodies against recessive epitopes in the NTD. This is what leads to the current situation, in which people suffer constantly elevated levels of respiratory disease. A lung environment populated with T cells looking for SARS2 has little room for other T cells looking for unrelated respiratory pathogens.
Through vaccination, you put abnormal antibody pressure on the Spike protein. This abnormal antibody pressure leads to affinity escape (escaping low affinity antibodies by increasing ACE2 affinity). But now that the abnormal antibody pressure is so strongly concentrated on the NTD, you’re encouraging the immunogenic loops of the NTD to grow shorter, which is known to dramatically increase fusogenicity. In other words, you are selecting more virulent variants.
It’s very simple: You want to see a small number of high affinity antibodies, against select regions of the Spike protein, in people who suffered severe infections. Those antibodies will be against regions that are associated with virulence. As a result, people will gradually offer a selective advantage to variants of this virus that are less virulent. What you don’t want to see, is this yellow line in the whole population:
This is what happened to the four hCovs in our species: We had a pandemic long ago (including one in the 19th century), a bunch of people died, then it gradually grew less virulent. But here’s what’s happening to SARS2:
It has been gradually growing more virulent since the first Omicron, but we don’t really notice it yet, as the most vulnerable people have already died by now. This happens, because the population is unable to select against virulence, because there is an antibody response against regions of the Spike protein that would normally not be targeted.
The previous failed vaccination experiment
I think this is just genuinely going to escalate dramatically.
Why?
Well, we can look at the attempt to vaccinate chickens against influenza in Asia. These vaccines began selecting new variants, they ended up breeding versions of influenza that are extremely deadly and focus on infecting the brain rather than the lungs. Those versions have now spread around the world and killed millions of wild birds, entire species have had more than half their population die in a single season.
SARS2 is happily proceeding along the same path, with vaccine resistant versions emerging that are getting better at infecting the brain and
increasingly competent at fusing cells together. In both cases we’re dealing with a virus that has an abnormal polybasic cleavage site, allowing it to infect endothelial cells.
If we’ve tried the exact same experiment of vaccinating against rapidly mutating respiratory viruses in another species and ended up breeding deadly viruses that decimate wild bird populations, wouldn’t you expect that performing the same experiment in our own species also results in deadly viruses that decimate our population?
You might argue to me that people now have immunity against proteins other than Spike too. But I don’t think it’s going to be very relevant, because you can only neutralize viral particles through Spike.
Immunity from interfering defective viral particles
So what about the unvaccinated? Well, I have explained most of the puzzle a few times.
But there’s one element I’ve never addressed:
interfering defective viral particles. This is not difficult to understand. When a cell is infected with the virus and does not get killed, but tries to get rid of the virus on its own, it will contain defective viral proteins or viral RNA. When it then gets infected again later on with a new variant, it will produce defective viral particles, that stimulate the immune system without being able to complete the viral cycle. These defective particles interfere in the normal particles replicating.
NK cells are aggressive upon a first infection, destroying infected cells. Upon subsequent infections however, they tend to prefer telling infected cells to solve the problem themselves. They have receptors they can use, to detect large chunks of weird RNA, which they will then delete. This means you end up with some persistent broken RNA in those cells, only activated again upon reinfection.
That’s a normal part of how immunity is supposed to work. It has a small protective effect on unrelated viruses, but a major protective effect on closely related viruses. Once you vaccinate people,
you tend to break this immune mechanism, as the cells capable of producing defective viral particles will get killed.
Once you make the antibodies and T cells do the job of dealing with this virus, you set the immune system up for failure, relying entirely on these two mechanisms that are very vulnerable to the effects of mutations to the Spike protein. Such failure could come very suddenly and unpredictably, as changes to cysteine bridges can cause the whole NTD to fold differently, thereby evading most antibodies.
So all these studies, arguing that the virus never leaves your body, are not discovering something shocking. They’re just discovering how the immune system works: It encourages infected cells to store broken genetic material of viruses, that interferes with their replication next time the virus shows up.
Sometimes this means the virus fails to spread in your own body, sometimes it means you pass on versions of a virus with reduced fitness. Vaccinate everyone with inactivated vaccines and you break this mechanism.
Solving the problem
The tragedy is that the immune reprogramming after vaccination is effectively permanent, it is merely recalled with every subsequent infection. The antibodies that bind to new versions of the Spike protein prohibit NK cells and other elements of the innate immune system from learning to properly do their job during subsequent infections. You can look at the antibody response to the newest JN.1 strain here:
Adults with two shots of mRNA:
Unvaccinated adults:
The immune system is still stuck with an abnormally elevated antibody response to this virus. As a result, the virus continues to be under pressure to shorten its immunogenic NTD loops and increase its fusogenicity.
In contrast, the innate immune system will have to do the job among unvaccinated adults. These are mechanisms that select against virulence.
The situation we’re dealing with, is one where the intrinsic virulence of this virus will continue to rise, until the antibody pressure exerted by the vaccinated is diminished.
Everything I’m saying here is a natural outgrowth of how the immune system works.
The main purpose of antibodies is to exert selection against virulence associated epitopes. That’s why
survivors of the 1918 influenza pandemic have antibodies that react with the 1918 pandemic, but not with modern influenza strains. These people who built up natural immunity, with antibodies against select virulence-associated epitopes, are the reason the 1918 strain of influenza was replaced over time by more benign strains: Their immune systems would only pass on more benign versions of influenza.
We broke that mechanism for our own short-term self-interest and made a handful of people billionaires in the process.