Trained innate immunity: The only way to prevent a pandemic of ever more virulent SARS2 variants

In light of India reviving its corona hospitals and novel variants now emerging with a 132% growth advantage in highly vaccinated regions of the world, I feel a moral obligation to explain what has me worried. I’ve already offered my best advice on how to respond to the problem here. By explaining what has me worried, I hope to motivate people to take my advice seriously. This is not a pleasant topic, but I feel obliged to address it. We don’t solve problems by pretending not to notice them.

This is a long post, but I think it’s the best one I’ve ever made on this subject and I expect you’ll learn a lot from it. I have tried to make this post useful and informative for individuals, as well as for academics and policymakers. I strongly encourage anyone who can further improve upon my work here to make it useful for a professional audience to do so, you can take all the credit yourself.

The idea that led people to endorse the SARS2 vaccine was that simply vaccinating everyone above 18 would push society beyond a herd immunity threshold. This is part of the reason the cost-benefit analysis never made sense for young adults: It didn’t need to make sense. Young adults were expected to risk their own health, for those who were at risk from the virus. It was thought that for the population as a whole this would be a net benefit, as the young would no longer infect the elderly.

The harder it proved to achieve the elusive herd immunity threshold, the more hostile society became towards the unvaccinated. Then finally Omicron emerged, leading public health officials to throw in the towel and concede herd immunity would not happen. The reduced virulence then led people to move on with their lives.

The problem of course, is that the virus itself has no clear obvious incentive to reduce its virulence in humans, at least not on a timescale of years. Hence why Alpha was more virulent than the original variant and Delta was more virulent than Alpha. The reduction in virulence seen for Omicron appears to have been a side-effect, caused by its origins in rodents. With reduced interferon suppression it won’t kill its rodent host (SARS2 is very lethal in rodents), the price it pays is a reduced infection length in humans, as our immune system figures out more rapidly that there’s an infection.

In relatively young populations with relatively strong natural immunity like India, what you witness is that Omicron variants are eventually suppressed as the population no longer sheds the virus in substantial amounts, it approaches local extinction. This is generally not seen in Western nations, where we see constant levels in sewage.

When the population’s immunity is strong and there is no easy path to avoid the population’s neutralizing antibody response, what you see is that changes emerge that interfere with the earliest steps towards triggering an immune response: The interferon response. Suppress the interferon response and the virus can spread in a population with strong immunity. The price humanity pays for that is increased virulence.

In India XBB.1.16 has accomplished this. It became better at suppressing interferon and as a result manages to spread again in a population that had built up a wall of immunity. You can read for yourself here that it doesn’t show superior antibody evasion to the other XBBs. In other words, its massive growth advantage would seem to be from the changes to non-Spike genes.

An important change seen in XBB.1.16 is eye inflammation. What this suggests to me is increased neurovirulence. It has been found in the past that eye inflammation is linked to higher severity. The authors of this study wrote:

An open issue is if conjunctivitis is a sign related to the route of entry of the virus in the human body or, more interestingly, occurs during a later phase of infection as suggested by previous studies showing that many conjunctivitis are detected after the onset of COVID.^4,8 If so, conjunctivitis could represent a sign of a systemic disease and a warning sign of poor outcome consequent to the systemic inflammation. This hypothesis may be supported by the multisystem inflammatory syndrome (Kawasaki disease) in children with COVID-19, where conjunctivitis has been described as a sign of a storm of cytokines and inflammatory molecules⁹ independently from COVID-19 infection.

People are now figuring out the pandemic is not over, we haven’t reached an endemic phase. We’re still stuck with a virus evolving towards increased virulence. This means we’re stuck with a looming problem. Natural Killer cells have receptors that detect viral glycoproteins, these receptors look a bit like the sort of receptors that viral proteins normally use to enter cells to infect them. If these NK cells approach a cell infected by a virus, these receptors are activated and the NK cell figures out it needs to kill the cell.

The receptors that seem most relevant for SARS2 are called NKp30, NKp44 and NKp46. They appear somewhat redundant, in that you need to block all three of them to allow SARS2 to proliferate. Any of the three is sufficient to allow the NK cells to destroy infected cells.

If the Natural Killer cell has one of these receptors stimulated and then also detects damage associated patterns (DAMP) and/or Pathogen associated patterns (PAMP), it will kill generally the infected cell. Because it has performed its job it will typically proliferate, leading to immunity through tissue-resident NK cells.

When you vaccinate someone with mRNA or the Adenovirus vaccines, you cause healthy cells to express a novel protein on their surface and in the MHC molecule. This triggers an antibody response and a CD8+ T cell response. You don’t expect it to trigger a substantial Natural Killer cell response, as the DAMP and PAMP relevant to SARS2 should not show up in a transfected cell, at least not in the mRNA transfected cells.

The problem is that during every subsequent infection, the antibodies are then recalled. Those antibodies will bind to Spike protein expressed by infected cells. This prevents the NK cells from finally learning to join the fight: With antibodies stuck to the Spike protein on an infected cell, the NK cells receptors can’t bind to the Spike protein expressed by these transfected cells.

This turns into a problem once interferon suppression increases through mutation, as the antibodies and CD8+ T cells that did the job of suppressing the virus are then no longer recalled.

There is another problem you run into. When you vaccinate with influenza peptides, you provoke regulatory T cells, which can then suppress immunity during subsequent influenza infections by different influenza strains. As a result the body struggles to clear the influenza virus. However, the regulatory T cells also impact the natural killer cells. Regulatory T cells can prohibit the proliferation of NK cells. I will return to this topic later on in this post.

The immune system is characterized by constrained immunological space. This is something many people sadly fail to understand. Different branches are in competition with each other, for the same limited amount of space available. Excessively provoking one particular type of immune response, will come at the cost of other forms. The immune response needs to be well-matched to the threats in your environment, so vaccines need to very closely match the pathogen they are supposed to protect against. It’s not like an operating system, where you can just endlessly dump new software as long as you have disk space.

Specifically, the evidence we have available suggests that we interfered in a massive way, prohibiting the proliferation of NK cells that express the NKp30, NKp44 and NKp46 receptors in the proper tissues where SARS2 shows up. This is a problem in the long term, because the NK cells with these receptors don’t require interferon to do their job.

The reason we have NK cells with these receptors is because this allows us to deal with a wide variety of virus families, that all tend to have similar characteristics. This is variant independent immunity. Over time you would also expect successive infections to trigger the proliferation of NK cells with adaptive traits, as different genes are hypermethylated or hypomethylated, allowing the population of NK cells to specialize for a particular job.

When NK cells take up residence in your organs, they tend to adjust to their situation. They become less trigger-happy, they don’t murder infected cells as often as circulating NK cells do. However, they do continue to release large amounts of interferon gamma whenever they notice a cell they think is infected by something nasty. They’re also able to release other signaling molecules, some of which serve to tell stem cells to produce large amounts of eosinophiles, subsets of which are very competent at breaking down viral particles and can release ribonucleases which will break down viral RNA in infected cells.

The interferon gamma is very important. Whereas other interferons are released by any sort of cell infected by something nasty, interferon gamma is an interferon released only by immune cells in response to a cell being infected. It’s an interferon that doesn’t just tell your adaptive immune system to kick into action, it tells cells exposed to it to activate all their innate defenses against viruses. In addition, it is a directly antiviral protein itself, it interferes with viral replication in numerous ways.

It’s good to have your NK cells take up residence in your tissues and stick around there to deal with nasty viruses like SARS2. You could have CD8+ T cells take up residence in your tissues too, but in organs like the brain that seems undesirable, as unlike the NK cells they seem to stay trigger-happy. You probably can’t afford to have cytotoxic lymphocytes attempt to control infection by killing your infected brain cells.

In general we can say that the immune system just has immune cells that evolved to deal with complex persistent viral challenges it has to struggle against. The NK cells play a dominant role in that response, they can often detect a cell displays signs of infection long before a CD8 T cell can and then they make a complex cost-benefit analysis of sorts before deciding whether to kill an infected cell, .

We don’t want to interfere with the NK cells learning how to deal with this virus.

As the tissue resident NK cells become less murderous over time, you can expect there will be viral proteins that continue to be produced by infected neurons and endothelial cells, with the interferon gamma released by these NK cells serving to prevent their assembly into active viral particles. This poses a potential problem, in the form of spike protein accumulating in the skull.

The best solution I have seen to this problem is for people to eat Natto high in Nattokinase, which degrades the spike protein. I will warn all of you again, you want to start addressing problems like spike protein accumulating in your skull, before you start noticing the symptoms. You need to be able to hear the Natto sizzle when you stir it, otherwise it’s low in nattokinase.

It’s important to understand however, that immunity is not just a job limited to your white blood cells. Every cell in your body has its own little immune system, that is responsible for helping it deal with exposure to various pathogens. To deal with RNA viruses, all your cells have receptors they can deploy internally, that look for RNA different from their own RNA.

Specifically, for SARS2 we have a receptor called MDA5, which is good at detecting large chunks of RNA. The SARS viruses produce large chunks of RNA, that for many of your cells look unlike anything they themselves produce. Your endothelial cells, the cells SARS2 preferentially infects, adjust through repeat exposure to viral RNA, by increasingly proactively producing the right receptors to recognize whether they’re infected by SARS2 viral RNA. This means receptors like MDA5 are produced more rapidly and in greater amounts. There’s no signs of tolerance over time either, two exposures to alien RNA makes the cells more aggressive to subsequent influenza RNA exposure than just one exposure.

It’s a mistake to believe that SARS2 infection is virtueless: It trains the innate immune system. And with more virulent varieties of SARS2 characterized by more potent interferon suppression ahead, we will be happy that people have already been exposed to less virulent varieties.

If the infections are constantly abrogated by IgG antibodies provoked by vaccination however, training of the innate immune system will lag behind.

It’s clear that vaccination hasn’t worked to end the pandemic, as the deployed antibody repertoire rapidly becomes mismatched to the dominant circulating strains. In fact, throughout 2022 excess mortality has continued mainly in highly vaccinated Western nations, increasingly affecting not just the oldest elderly, but younger age groups as well. The only European nations showing negative excess mortality in recent months have been Bulgaria and Romania, which happen to have the lowest vaccination rate.

However, we still haven’t seen the full impact of the collective mistake that has been made. The reason is because SARS2 is still evolving. The first stage has been evasion of the neutralizing antibody response through mutation of the Spike protein. We’re now entering a new chapter, where activation of the adaptive immune response is increasingly suppressed altogether.

When you compare SARS1 to SARS2, what you’ll notice is that SARS1 is more virulent.

However, what’s important to understand is that SARS2 is learning some of the tricks that SARS1 had available to it. Both XBB.1.9 and XBB.1.16 share Orf9b:5T. XBB.1.16, now responsible for such a massive surge in India, also has 55S in this gene. Now have a look at how SARS1 looks in this gene:

You can see these mutations make the gene look like it does in SARS1. Other mutations seen in chronic infections also make the gene look like it does in SARS1.

When the population has a homogeneous antibody response that imposes narrow selective pressure on Spike, the virus can survive by mutating its Spike protein. Once the antibody repertoire in the population diversifies through waves of variants infecting parts of the population, antibody evasion through Spike mutation as a survival strategy runs into limits.

That’s the point we’ve reached now. The rate of Spike mutation appears to be slowing down and there is now growing pressure on non-Spike genes to evolve in a manner that prohibits triggering an antibody and CD8+ T cell response altogether, with enhanced interferon suppression serving as a potent strategy to accomplish this.

The NK cells are prepared for this. The NK cells have natural cytotoxicity receptors that allow them to detect a cell is infected, even if the cell does not release interferon and does not display viral peptides in its MHC molecule. And so what you want to see, is that our population now has tissue resident NK cells after multiple infections, that have learned how to deal with viral infection and are not very trigger-happy anymore in all the relevant tissues, focusing more on releasing interferon gamma and other signaling molecules, tolerating SARS2 infection if the cell does not show severe signs of distress.

Unfortunately, we seem to have undermined the buildup of such innate immunity. This is why I worry that novel variants with improved interferon suppression will prove to be much more dangerous in highly mRNA vaccinated nations than in nations like India where they emerged.

The general tendency is also for viruses with improved interferon suppression to be more virulent. If it’s harder for the immune system to detect infected cells, it can spread further before the immune system goes on high alert, thus resulting in a more severe disease course. Most very deadly bat viruses are known to have very potent interferon suppression strategies.

A question you might have is “why doesn’t this apply for influenza, why doesn’t influenza vaccination screw up our immune response”? The answer to that question is that the coronaviruses in general and the Sarbecoviruses in particular just intrinsically have much more potent Interferon suppressing genes than influenza does, hence their general high level of virulence. Even hospitalized influenza patients show an interferon response that hospitalized COVID patients just don’t show.

Trying to protect people against a new virus by inducing an antibody and CD8+ T cell response, when that virus has the evolutionary capacity to learn how to suppress the interferon production that would recruit the adaptive branches of the immune system, is a dangerous idea.

The manufacturers of the vaccines people received treat this virus as if it were a kind of influenza, that simply changes its receptor binding domain every once in a while and thus necessitates an updated antibody repertoire for us to remain protected against this virus. But that’s not the case. This virus is going to increase its fitness and improve its ability to suppress interferon, so that your plasma B cells and your T cells don’t know that a particular cell is infected. They will either require your NK cells to recruit them to the fight, or they will respond late after an infection has been established.

But the NK cells, as explained earlier in this post and here in my previous post, would be expected to suffer interference from the adaptive branch of the immune system after vaccination.

So what you would expect, is that the increasingly virulent interferon suppressing strains constantly recall an antibody response that kicks in increasingly late. By then binding to Spike glycoproteins expressed on the infected cells surface and encouraging CD8+ T cells to kill the infected cells, they continue to interfere with NK cell proliferation and adaptation to the tissues they’re supposed to take up residence in.

But it’s worse. As I mentioned earlier, vaccination with peptides can lead to expansion of regulatory T cell populations, which are anti-inflammatory CD4+ T cells that prohibit an overexuberant inflammatory immune response. Those regulatory T cells prohibit the proliferation of canonical NK cells, only adaptive NK cells escape this interference.

In line with the general pattern where the mRNA vaccines appear to provoke a tolerogenic immune response I have explained many times on my website by now, we see that whereas the Adenovirus vaccines suppress the regulatory T cell population, the mRNA vaccines have been found to increase the regulatory T cell population.

And you can tell the authors of this paper are genuinely upset and worried. They explicitly write:

This pilot study is very preliminary, suffers from important limitations and, frustratingly, very hardly can be refined in Italy because of the >90% vaccination coverage. Thus, the provocative perspective that BNT162b2 and MOGm1Ψ may share the capacity to promote expansion of Treg cells deserves confirmatory studies in other settings.

And they’re not being very subtle here either:

Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that induces in mice robust expansion of antigen-specific regulatory T (Treg) cells. The Pfizer/BioNTech BNT162b2 mRNA vaccine against SARS-CoV-2 is identical to MOGm1Ψ except for the lipid carrier, which differs for containing lipid nanoparticles rather than lipoplex.

Well, they should be frustrated. If these vaccines have triggered a tolerogenic immune response, that also interferes with the proliferation, tissue-residence and adaptation of NK cells that recognize the earliest signs of infection, then that’s going to cause massive trouble, as the virus evolves to learn to get better at suppressing the interferon response produced by infected cells.

And this is not the only route we have to worry about. Let’s say the vaccines actually do the job they’re supposed to do, they succeed at abrogating infections, so that the virus never takes up residence in the brain, never takes up residence in the kidneys, it shows up in the upper respiratory tract and the adaptive immune system immediately kicks it out. That’s nice, until you’re faced with variants against which the antibody response has grown useless, that also have increased virulence. That means the rest of the body has received no training against milder versions of SARS2.

More than half of the 30 genes SARS2 is endowed with are linked to Interferon suppression in one form or another. You can be pretty sure that it hasn’t exhausted its potential yet. It will get better at suppressing interferon. And as it gets better at suppressing interferon, its intrinsic virulence will increase.

It’s important to understand the following principle:

The more the population’s immunity against SARS2 depends on the adaptive branch of the immune system (antibodies + T cells), the more selective pressure there is to increase Interferon suppression, because Interferon is necessary to alert the adaptive branch of the immune system.

Improved interferon suppression leads to increased virulence, regardless of whether infected people happen to be vaccinated. It seems to consistently lead to increased cytopathy for the infected cells too.

IN CONTRAST, we find that NK cells select AGAINST VIRULENT INFLUENZA STRAINS. Strong trained innate immunity, characterized by proliferation, migration and adaption of NK cells to the tissues they take up residence in would be expected to select AGAINST VIRULENT VARIETIES OF SARS-COV-2. And this makes perfect intuitive sense, if you remember: NK cells do not just check for signs of infection, they have a complex cost-benefit analysis to make, so complex the literature has only just begun to explore it, before deciding whether to kill an infected cell. They kill an infected cell if they see signals suggesting the cell is distressed. If the cell is not distressed they will not kill it, thereby selecting against strains that damage the cells they infect.

How did the 19th century coronavirus outbreak and the highly virulent 1918 pandemic influenza ultimately result in viruses with low virulence? The most sensible explanation to me is that NK cells selectively tolerated persistent infections by mutated viruses characterized by reduced cytopathic effects. The interferon suppressing genes also tend to damage all sorts of machinery in your cells, so selection against cytopathic variants would be expected to reduce interferon suppression too.

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Looking towards the future

What we really need right now, in an effort to solve this, is the most difficult thing to get. To figure out what you screwed up, you want to know what the NK cell population in tissues of mRNA vaccinated and unvaccinated naturally immune people looks like. But you can’t very easily take slices of organs out of healthy living people and examine this. You would have to look at dead people. You can’t just take samples from people’s blood and observe this, as that’s not where these mature well-adapted cells live. They’re known to take up strategic positions in our organs, in the exact places in those organs where a virus would first be expected to show up.

Once you know what the NK cell population is supposed to look like, then you can start looking towards ways to fix the problem you created. Maybe if you suppress the antibody response and get rid of the interfering regulatory T cell population, NK cells can get another chance at proliferation, migration and adaptation upon exposure to a live attenuated virus. This is something that would have to be studied.

And I will say this again, you want to fix the problem you created, because your vaccine didn’t work, there’s no denying it at this point. We have consistent excess mortality, increasingly showing up in younger age categories and concentrated in nations with high mRNA vaccination rates. And in contrast to India, where viral RNA in sewage is suppressed near zero outside of waves, viral RNA in sewage in the Netherlands looks like this:

What you see here is a population failing to rid their bodies of a sarbecovirus, with even the depths of SARS2 waves generally exceeding the heights of pre-vaccination waves.

This is not acceptable. It doesn’t just mean that you created a situation where the population constantly gets reinfected. It means that you created a situation where numerous people stuck with a tolerogenic immune response are host to persistent infections. Some of those persistent infections will suffer fitness reducing mutations, but other infections will learn to get increasingly better at suppressing the immune response.

If I thought this was just a shitty vaccine and SARS2 turned into another hCov I would’ve moved on with my life and stopped focusing on this. But that’s just not what happened. What happened is far worse. They damaged the immune response, in a manner that will force a virus to evolve towards greater virulence. They bet everything on the antibodies and the T cells, but that’s not how our bodies would normally deal with viruses of this nature.

And it’s not just me arguing this, the studies I cite are coming out on a regular basis now, arguing that the mRNA vaccines induced a tolerogenic immune response, but a handful of academics read them and everyone else would be left in the dark if I didn’t write about them. And I don’t benefit in any way from arguing this, I would benefit much more from these vaccines being genuinely effective, not just because most of my family and friends received these vaccines, but as it would mean I would cease to be constantly exposed myself as well. I have tried to the best of my ability since I first learned about these vaccines, to explain why they were a bad idea. I have tried to offer the best information and explanation I can.

Zinc and Vitamin D are useful to strengthen the innate immune response and suppress an overexuberant adaptive immune response. Natto is very useful, both for its vitamin K2 and its nattokinase content, as well as for the healing effect it has on the endothelium. You’ll have to make sure your natto genuinely sizzles when you stir it, otherwise the nattokinase content is very low. There is also consistent evidence that a plant based diet protects people.

But these are not lasting solutions and I wouldn’t argue such a thing. In the long run, there is just one solution: Reduction of the population’s adaptive immune response to this virus that is causing selection of virulent strains, in favor of strong trained innate immunity, which may result in herd immunity, or it may result in tissue resident NK cells in chronically infected people selectively tolerating the proliferation of attenuated SARS2 variants that do not cause distress signals to emerge from infected cells.

What would actually save lives is if people would look at how NK cell immunity has been interfered with through the mass vaccination program and then work on ways to address that problem. But almost nobody is interested in that. They went for the bizarre approach of trying to constantly maintain elevated IgG antibody titers through constant vaccination, when the evidence we had showed that natural immunity effectively protected people against reinfection without requiring constantly elevated IgG antibody levels. This isn’t just a bizarre approach, it’s also an unsustainable one, with the evidence now clearly showing T cell exhaustion after three doses.

What they need to do, is to compare people with natural immunity and vaccine induced immunity and figure out what elements of the immune response have been interfered with. The negative efficacy of these vaccines is no longer an obscure substack pipe dream. If your desire is to promote the public’s health, you need to start panicking when you get graphs like this:

If it was just my personal hobby to cook up some awful doomsday scenario, you wouldn’t be getting graphs like that in the scientific literature. If it looks like I’m trying to cook up an awful doomsday scenario, it’s because I’m trying to the best of my ability, to explain to you what is currently unfolding.

I’m still operating here from the framework that officials actually want to keep the general public healthy, which grows more doubtful by the day. To solve this problem, they need to come clean and admit that they screwed up, that they damaged the population’s immune response against a Sarbecovirus that’s now infecting people twice a year or more.

They need to do this to rewin the public’s trust, so that people will be willing to cooperate with therapies that would allow recovery of branches of immunity that have been damaged by the vaccination experiment, which might then bring about herd immunity. As far as I can tell, the constant lying and unwillingness to admit mistakes by virologists and public health officials is what got us into this situation in the first place. I expect that as long as that continues the crisis will just get worse too.

It’s possible that the innate immune response can be healed when people are exposed to a live attenuated virus that has had some of its ORFs deleted and/or suffered codon deoptimization. It’s possible, I don’t know, but the only way we’re going to find out is by people first ACKNOWLEDGING that this vaccine was a terrible, terrible mistake.

The longer it takes to acknowledge the vaccination program was an error that sidelined the innate immune response, the less time will be left to research, develop and deploy therapies before the virus reverts to high virulence.

In warning you about this, I have sought to fulfill my obligation to the best of my ability.