Doom, gloom and IgG4 boom

Dr. Geert vanden Bossche who is our ultimate guide for attempting to predict SARS-CoV-2 pandemic outcomes has released more material, specifically focusing on how the IgG4 antibodies fit into the current state of the pandemic and its future. In case you are not familiar with his prognostications, Dr. Bossche predicts that eventually, the pandemic will become more deadly. Even more deadly than what he had seen before the vaccines were available, in the first year of the pandemic.

We do not necessarily want to agree with that prediction but we do admit that Dr. Bosshe’s theory successfully predicted outcomes before (the immune escape by the virus where everyone started to get infected or re-infected) and can scientifically explain what we have seen all along. So careful attention is given to Dr. Bossche’s published information.

In the meantime, Merogenomics has been obsessed about IgG4s, as seen by our growing number of videos dedicated to the topic: a topic we deem absolutely crucial to the well-being of mRNA vaccinated!

We know that these IgG4s show up almost entirely in mRNA vaccinated who have not been infected first. If they have been infected prior to being vaccinated, it appears they will be fine.

And all of this fits Dr. Bossches overarching theory and he already started fitting IgG4s into the picture when his book on the current pandemic came out (which we reviewed here). So when he released a big update on IgG4 in relation to immune escape pandemic theory of his, we dove deep!

As in previous writings, admission needs to be made from the start that we barely can hold on with understanding the theory, it is that complicated. It involves many moving parts that are perhaps natural and simple to understand, but if you cannot connect the dots together, it is like learning a new language!

Keep that in mind as we start this article.

Disclaimer: this article could be very upsetting to read, especially for mRNA vaccinated. Remember, when discussing the future, everything is just a theory. Anything discussed might not turn out to be real. Due to the desire to abide by precautionary principles, we discuss this upsetting information to learn about solutions in a scenario where the upsetting theory does come true.

First, the take home message: his theory remains intact. Thus, expect the pandemic to lead to more pathogenic variants of the virus that will become very deadly. mRNA vaccinated especially are expected to be in jeopardy. IgG4s are a contributory factor toward that outcome, and their current observation in mRNA vaccinated individuals signifies that virus evolution is proceeding in that direction.

It also signifies that as a population, our immune systems are becoming less sensitive towards recognition of foreign invaders while becoming hyper sensitive towards recognition of self. It creates a bizarre sounding situation where disease symptoms are not apparent (reduced sensitivity to foreign invaders means less inflammation), while cancer and autoimmune conditions could be on the rise (due to cloaking of cancer from recognition, or recognition and destruction of healthy own cellular targets that should not have been targeted, respectively).

Yeah, we warned you, his stuff is dark. Again, please proceed with caution.

Omicron - the great divide

To start recapping a bit, the pandemic can be divided into two phases.

Pre-Omicron and post-Omicron emergence.

Pre-Omicron phase lasted about two years, with the first year dealing with a natural pandemic, and the second year marking the mass vaccination. Since the end of 2021, we are in the Omicron era, where the Omicron with its mysterious evolutionary history resulted in immune escape, where the virus changed enough to be able to escape antibodies of both the vaccinated and those who had natural immunity from prior infection.

Since the Omicron, everyone and their dog got infected it seems, but the severity of the COVID-19 disease practically disappeared in comparison to what was seen pre-Omicron.

It seems, the current preferred dogma of the scientific and medical authorities appears to be that we have reached herd immunity, thanks to all the vaccinations and infections, and the virus entered an endemic phase characterized by its more benign state. Along the way, we keep seeing constantly new variants popping up (without explanation as to why we see so many, so that remains a mystery), and to remain protected against these emerging variants, boosting with vaccines is recommended. Boosting appears to provide good protection short-term, and data after data appear to support this. Unfortunately, this protection is really short lived (antibodies disappear really quick, also without explanation as to why, so that also remains a mystery), so frequent boosting is needed. The entire situation with SARS-CoV-2 starts to look like dealing with influenza on a yearly basis, although SARS-CoV-2 looks more like it is on evolutionary steroids in comparison to influenza. Since hospitalization and deaths are waaaaaaaay down (thank goodness!), the situation looks stable so we are not deviating from this approach and reasoning.

Bossche says bollocks!

Along the way though there have been reported very strange observations, that also remain a mystery. There have been reports of an overall increase in all-cause mortality in our population, and there have been ongoing persistent rumours of increased rates of cancer (to Merogenomics prying eyes, unsubstantiated by science at this moment) and apparently lots of cases of infection.

So what is going on?

Before the Omicron, vaccines or natural infection induced neutralizing antibodies directed against the spike protein. At first, these were high quality antibodies, produced through assistance from T cells that were recognizing the same dominant spike protein targets (referred to as cognate T help).

But quickly virus was mutating and producing new variants. These variants when infecting the people were triggering recall of both T cells and antibodies to previous variant that started the pandemic. This is referred to as ‘original antigenic sin’ or imprinted immunity. As a consequence, these recalled T cells and antibodies were no longer the same high quality match against the new variants. Those who got infected could end up with even severe infection symptoms and provided grounds for the virus to evolve against the imperfect immune attack.

Since Omicron, the ‘original antigenic sin’ was no longer happening because while infections were taking place, the disease symptoms were now typically mild. Milder symptoms meant that less virus was produced, and hence recall of the previously neutralizing antibodies and T cells should have easily dealt with infections. Something else was afoot.

Rather, the presence of poor quality antibodies and recall of previously cognate T cells resulted in these poor quality antibodies actually masking the dominant areas of the spike protein. This masking of the dominant sites of the spike protein forced the immune system to produce antibodies against different areas of the spike protein. This is referred to as immune refocusing, and is different from ‘antigenic sin’. In essence, because new areas of the spike protein were now targeted, not the dominant ones, and the recalled T cells that were helping the B cells in the production of these new antibodies, they were no longer cognate help because these B cells and T cells were mismatched in what they were recognizing. This is referred to as non-cognate T cell assistance. Such non-cognate assistance leads to the production of weak antibodies. This in turn means infecting virus is not going to be dealt with properly, providing fertile grounds for the virus to survive the attack by the antibodies and evolve further away from them. Thus more immune escape by the virus. This also explains why these antibodies always showed short lifespans and quickly start disappearing post vaccination. Also, these antibodies were not targeting dominant areas, but rather sub-dominant areas that typically would not be under immune attack. Because these areas are typically not attacked, they also happen to be conserved among different coronaviruses, and can target many different variants as well (therefore these are broadly cross-neutralizing antibodies).

You may think to yourself, well, isn’t that good? This is probably what many scientists and experts in positions of authority are also saying. This is why everyone gets all excited for few weeks post booster because boosters trigger the production of massive amounts of these antibodies. But they appear to do a good job not on account of being high quality, but rather through a brute force approach of creating many poor quality antibodies. Along the way, we are duping ourselves that we got something that works, when it does not, and even contributes to harm.

On top of pushing the virus evolution, because these new target areas on the spike protein are conserved areas typically not targeted, they can also exhibit similarity to the shapes of molecules found in our body. Therefore immune refocusing also runs the risk of inducing the ability for the new immune response to also target new targets of our own body.

This phenomenon of immune refocusing was not observed in anyone who had properly trained innate immunity by a prior viral infection. Why? Because such training reduced the levels of the virus enough through the use of innate immunity to reduce the likelihood of observing immune escape. We get to more on that in a moment when we discuss antigen presenting cells.

This is finally where we are going to switch to IgG4.

IgG4s are a calling card of the immune escape pandemic taking place

Because the immune refocusing took place, meaning new areas of the spike protein were targeted, and the resulting antibodies were not induced to be high quality (due to lack of cognate T cell assistance), the maturation of these antibodies was a prolonged process, and along the way, due to the extended period of time during which the B cells responsible for the production of these new antibodies were maturing, they kept encountering the spike protein again and again. With all that encountering of the spike protein, the B cells were induced to switch their production from IgG1 class of antibodies (used by immune killer cells to remove the insult but also cause inflammation) to IgG4 (which cloak the insult and remove the inflammation experience). You can think of the bee keeper analogy. There is no point to constantly experience inflammation from bee stings if they are going to be experienced again and again by the bee keeper, so the body switches antibodies to IgG4 kind of antibodies that now react to the bee sting, and protect the body from unnecessary frequent inflammation.

And IgG4 antibodies, with their broadened but weakened targeting of the spike protein, themselves induced a second round of immune refocusing! This means these IgG4s were responsible for pushing even further virus evolution towards even more and more infectious variants, exactly what we have been observing taking place for the last couple of years. Of course, with a second round of immune refocusing, it means the targets on the spike protein got even worse, targeting even less dominant sites (or sub sub dominant sites to what was originally targeted at the start of the pandemic). And once again, the production of these antibodies against another set of new spike protein targets was also achieved without cognate assistance from T cells, so another round of weak antibodies that once again led to IgG4s.

In essence, two immune refocusing events took place since the Omicron took charge of the world, both resulting in IgG4 antibody production. Along the way, due to the anti-inflammatory nature of IgG4 antibodies, the symptoms of infections that are taking place left and right are masked, and we are none the wiser about our merry spread of the virus all around.

And remember, with this second round of immune refocusing, going after even worse target sites of the spike protein, we are now targeting even more conserved sites of the virus shared between coronaviruses, and that means even more likely we are targeting sites that could be also now recognized in our bodies.

Thus IgG4s are a telltale sign of both immune refocusing taking place as well as immune escape taking place as a consequence of the immune refocusing impacting the viral evolution. And since we ended up targeting more conserved sites of the virus that would not typically be challenged, the IgG4 antibodies are also a sign of an expected rise in autoimmune diseases and cancers.

The likelihood of mRNA vaccinated individual who did not have their innate immunity trained (were not infected by the virus prior to vaccination) to develop the autoimmune disease or cancer will depend on how much time has elapsed since their second exposure to the spike protein (so either two mRNA shots, or one mRNA show followed by infection), and any additional spike protein exposure (either booster or infection) should enhance the possibility. The type of disease that might develop will depend on the virus variant involved in the process as different variants can exhibit nuanced differences in their spike protein shape, enough to result in differences in disease outcomes.

Along the way, we have been gifted with more and more infectious versions of Omicron variants (this is where we are now), and it is these super infectious Omicron descendants that are going to drive the evolution of the virus towards the more pathogenic state. And IgG4 will also play a role in that.

SARS-CoV-2 to become a monster?

These new highly infectious Omicron descendants are so darn good at infecting that they will no longer be able to induce another round of immune refocusing. Hence we are now on the path towards more pathogenicity. The reason for this, according to Dr. Bossche (if understood correctly, and remember, that is an important caveat), is that the super infectious virus now activates our antigen presenting cells to the max. These are the cells that present the pathogen fragments to the immune system to let the immune system know what to target. They also trigger the activation of cytotoxic T cells that kill infected or damaged cells in our body. And since antigen presenting cells are so super activated, this means cytotoxic T cells are also activated over time, so much so, that in the killing frenzy that ensues, they even start killing the antigen presenting cells themselves. Seems like anything with a hint of pathogen gets wiped out instantly. And with antigen presenting cells rapidly removed, there are no additional spike protein fragments presented to the immune system to induce the production of a new set of antibodies, and hence no more immune refocusing.

This also is why boosting with updated boosters will no longer work in terms of inducing new antibodies against the latest variants. Again, if antigen presenting cells are rapidly removed, there is no triggering production of new antibodies. No recall of helper T cells to induce B cells into antibody production.

All we are going to achieve is a recall of the same IgG4 antibodies, once again, through ‘original antigenic sin’.

How are these IgG4s expected to help push the evolution of the virus toward more pathogenic variants?

Here is where Dr. Bossche is placing his bets on his seemingly unique knowledge: he believes that both mRNA vaccination, as well as reinfection with more infectious variants against the background of untrained innate immunity and weakly neutralizing antibodies, also leads to the presentation of the spike protein in an aggregate manner, either on the surface of cells that took up the vaccine, or due to clumping of too much virus released post infection. This aggregation presents the spike protein in a slightly different manner than it otherwise would be when present in lesser amounts and not having the opportunity to aggregate. This unusual presentation is what can trigger the antigen presenting cells to go bannanas and over-activate the cytotoxic killer cells we discussed already. But it can also lead to the production of antibodies that recognize this type of aggregate spike proteins pattern. These antibodies are produced by B cells even without any help from T cells, thus they are very short lived antibodies. He likes to call these poly-reactive non-neutralizing antibodies. These antibodies play a couple of key roles. First, they used to help the virus be more infectious because they helped the virus bind to our receptors even more, which they still can but the virus is now so infectious, this benefit is not as valuable as when Omicron first emerged. Second, they bind the spike protein in a place that previously was also being captured by immune cells (called migratory dendritic cells) that could inadvertently bring the virus from the upper respiratory tract to lower respiratory tract and lungs. As a consequence of these poly-reactive non-neutralizing antibodies, we had the benefit of reduced disease symptoms as well (because the infection was not spreading to the lungs where it had a chance to become seriously dangerous) but the virus became more infectious.

This paradox is another unexplained mystery by the authorities: how do you get a more infectious virus that is milder in outcomes?

Every mRNA vaccination or breakthrough infection of a vaccinated person would stimulate the production of these poly-reactive non-neutralizing antibodies due to the constant abnormal presentation of the spike proteins in these clumped arrays.

Now that we have IgG4 in the neighbourhood of the upper respiratory tract though, IgG4s can start to inhibit this clumping of the virus particles post infection. Why? Remember, IgG4s are made to hide something from being recognized by the immune system, and one way they achieve that is through their special design that diminishes clumping of what they bind to (antibodies like to clump their targets, so that they form a big bullseye for immune system recognition). And as we now have less and less aggregation of the spike protein into these clusters, there is now less opportunity to induce the production of poly-reactive non-neutralizing antibodies. But remember, these poly-reactive non-neutralizing antibodies happen to prevent the migration of the virus to other sites of the body, including the lungs. Therefore, as you reduce the level of poly-reactive non-neutralizing antibodies, now you give a window of opportunity for the virus to start evolving to completely bypass this protective effect of poly-reactive non-neutralizing antibodies. This would mean the virus will now be evolving back in a direction where it could be transported to other body sites. Once it achieves that, the outcome of infection will be a more serious disease than the milder version we have been seeing post-Omicron era. In other words, the virus will become more pathogenic.

How did those poly-reactive non-neutralizing antibodies achieve the reduced migration of virus particles via dendritic cells to other organs? Apparently, these dendritic cells (which by the way, are a type of antigen presenting cells) were latching onto sugar molecules adorning the spike protein, and poly-reactive non-neutralizing antibodies reduced that interaction simply by the nature of where they bound the spike protein. But Dr. Bossche now believes that as IgG4s reduce the protective effect of poly-reactive non-neutralizing antibodies with an opportunity to start reducing the protective effect of poly-reactive non-neutralizing antibodies by IgG4s, the virus through random mutagenesis will eventually produce mutations that will lead to new sites of sugar attachment on the spike protein. This new sugar pattern will re-establish the ability of migratory dendritic cells to grab virus particles and move them to other body sites.

Once that happens, we will be back to the previous scenario of infection potentially leading to serious disease. But this time around we are dealing with far far far more infectious virus than before, and on top of that, due to mRNA vaccinations, also untrained innate immunity in those who took the vaccine without being first infected by the virus. As a consequence, this will trigger a wave of severe disease that will be very dangerous to the vaccinated population.

He thinks this will be so catastrophic in its consequences that it will lead to such an enormous amount of deaths, that it will actually kill the virus from existence because the virus will no longer have enough hosts!

Yeah, you can see why no one is a fan of his theories, except the most bitter non-vaccinated people who took a moral beating during the pre-Omicron phase where everything in the world was blamed on the non-vaccinated.

But is there hope?

Vagus nerve to the rescue? Or rather, rescue the vagus nerve?

You bet! Here is where we depart from Dr. Bossche and Merogenomics has been on a quest to find loopholes to keep these hopes alive. Admittedly it is not easy when presented with such a complex scenario that can be barely understood. But let’s not succumb to that grim scenario that easily!

Before we go on, in case you were curious what mRNA vaccinated could do to protect themselves in case his doomsday scenario does come true, see Merogenomics review of Dr. Bossche’s book on the immune escape pandemic.

Here is where we extend the hope of his plotting missing some component that perhaps will lead to different outcomes. No way do we want to think that mRNA vaccinated will start dying en masse.

And the one missing component that is completely missing from Dr. Bossche’s universe is the vagus nerve!

As of late, Merogenomics has jumped on the vagus nerve bandwagon as a potential element that could justify the myriad of complex symptoms of long-lasting spike damage. This all started with our journey into pathology related to the spike protein, specifically, how the spike protein could be involved in the formation of abnormal amyloid clots that you can dive into below.

By the way, amyloid refers to assembling into an abnormal array, similar to what we discussed above with regards to spike protein invoking the production of poly-reactive non-neutralizing antibodies. What was intriguing about these studies of abnormal cots is that different virus variants had different capacities to induce these clots, and the Omicron variants had dramatically reduced capacity to trigger these clots in comparison to pre-Omicron variants.

The authors whose work was analyzed proposed a series of potential treatments (see the second to last video in the above series) and one of them was the vagus nerve neuromodulation.

Where it gets interesting is that the vagus nerve was suspected early on in the pandemic and computational modeling studies have been done on whether the spike protein could be binding to vagus nerve main receptors, the acetylcholine receptors. And it turns out there was a good match. But once the spike protein mutated to Omicron, that interaction was severely compromised, it was no longer a good match.

So this begs the question: could much of the symptoms related to spike injury be due to its interaction with the vagus nerve? And could the reduced pathogenicity of the SARS-CoV-2 virus be dictated at least to a degree by that interaction with the vagus nerve?

The reason why this is so appealing, apart from a potentially easy treatment option for the spike related injuries, is also that it adds a layer of complexity that might not be as easy to overcome on the path of virus increased pathogenicity as creating the sugar bridge for migratory dendritic cells that Dr. Bossche is talking about. Dr. Bossche has been warning about the imminent rise in deaths for nearly three years. Supposedly we are in the last stage of virus evolution towards enhanced pathogenicity. But what if it is not just the movement of dendritic cells from one body area to another? What if the vagus nerve needs to encounter the virus and that requires the spike protein to properly bind to acetylcholine receptors to see the same level of disease as we did before? Then Omicron is so far gone in its evolution from the early variants that perhaps such binding is not going to be seen again.

And perhaps along the way, there will be additional evolutionary events in the virus, or in immunological responses to it, that we will see SARS-CoV-2 become endemic without this doomsday scenario unfolding.

So yes, we want to cling to hope. Hope that there might be an easy solution for some to heal from injuries, and hope that more suffering is not on its way.

Time will tell how it all unfolds. But we prefer to cling on to that hope.

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