GGeert_Symposium_March2022.md 18 KB
We are now going to take a deeper dive in hte vaccination topic that was heavily debated nowadays
I am worried about mass vaccination inevitably driving immune escape - force the virus to escape the immune respon ethat is actuall induced by those vaccines. Of course, I will come to this in a moment. I think the slide of the publication is just illustrating that basically this has already been documented in th eliterature. If you vaccinate animals with a vaccine that prevents disease but doesn't prevent infection, you force the virus to select mutations that enhance its infectiousness.
We are no longer dealing with the natural course of a pandemic. Interventions nad mass vaccination on a massive global scale. None of this existed in teh previous pandemics, such as the WW1 pandemic wththe influenza pandemic, where we observed the natural course of a pandemic.
This is a complex interaction between the virus and the immune system, and if you dnot' understand this phenomenon, if you don't understand the natural course fo a pandemic, then I think you have no right whatsoever to intervene in that course hoping that you will shift this into a kind of course that will be more beneficial for human kind. I will show you that it is exactly the opposite that we are doing now.
In simple words, the first wave is easy to understand. The virus is new to the opopulation, nobody has antibodies. But, some people, and actually a large part of the population, has a strong innate immunity. I will come back to this and explain why this works. What we have witnessed how, for example, elderly people, people with underlying diseases that are otherwise immune compromised, are more vulnreable to getting the disease. tHis is something that has been very obvious from the beginning of the pandemic. These people get the disease, majority will survive, some will die. But then there is an interesting thing - if you are dealing with a complex thing like a pandemic, and you don't understand all the observations made - and some things are mysterious - you cannot intervene. You cannot afford to leave any stone unturned, because the second wave,f or example, the second wave of that pandemic was hitting the younger population. The second wave was a severe wave, and it was very focused on making young people ill. This was a huge problem in WW1, of course, because more soldiers died of influenza in the trenches than there were dying of wounds or injuries from the war.
So, how can you explain this? How can you explain that these people, I was just saying because of their strong innate immunity, were protected during the first wave, and then all fo a sudden they get massively hit by disease during the second wave. And then there is a third wave, and then we see that the pandemic is transitioning into what we call an endemic phase where you can have flare-ups, but basically you get a notion that we are all aware of - the ultimate goal also of the vaccination - herd immunity.
Let me explain how that works. The fact that we have, essentially, the second wave hitting younger people.
BEfore we get to this, we should first have an understanding of a phenomenon that is not well understood. All the pulications still say that COVID remains mysterious and that we don't have an understanding the pathophysiology. There is a need to understand this better. But, again, how can you proceed with immune interventions if you don't even understand how the virus is interacting with the immune system. Where is the science that allows us to intervene when we don't understand this?
What is happening is the virus comes in, at the upper respiratory tract, and you have epithelial cells that are susceptible to the virus, and then the virus can neter into this cells by docking on on a receptor. Once the virus gets into the cell, it can start to replicate, it will dstroy the cell, the virus will be released, and when the virus further propagates to the lower respiratory tract, for example, and to the lungs, there you can get more severe disease and we all know that that is the place or the piont in time where you may get cytokine stormes or heavy inflammatory symptoms where people need to be hospitalized.
But there is another interesting phenomenon - and if there is one thing in the whole covid pandemic and the understanding of the pathogenesis o the disease then it is the situation and the cycle of the virus in people that don't get symptoms. So why are people getting symptoms and others are not?
Well, it's innate immunity - but how does that work? And how can you basically explain that the vast majority of the population, and not just youngers - even some elderly can be perfectly protected by their innate immunity - and we don't understand exactly how that is working and that is a major shortcoming. The arm of the immune system that has been completely neglected in the whole consideration of how this pandemic spreads amongst the population is the innate immunity. The immune system has two arms - the innate and the acquired immune system. The acquired immune system these are teh specific antibodies that the body will build once we have gotten a disease and you build antigen-specific antibodies - and those will prpotect you. But we have the other arm, which is the innate immune response - this is not antigen or variant specific it is not even corona specific. It can cover a large amoung of different viruses - certainly all corona viruses - all variants of covid. How does that work?
It works through Natural antibodies. The natural antibodies are already present at birth. Especially children have a strong reservoir of natural antibodies. These natura lantibodies are secreted by certain immune cells that are very-well presented in the young immune system.
These natural antibodies - what do they do? Well, they can complex with the virus. They can recognize the virus and build a complex with the virus and then this complex is, in fact, internalized intow hwhat we call antigen-presenting cells.
Antigen-presenting cell is a cell of the immune system that is going to internalize a foreign body - a virus - and is going to digest that virus and then present the pieces of that virus - the epitopes - on its surface of the antigen presenting cell - and that is basically required in order fo rthe immune system to well-recognize the pathogen. The pathogen is cut apart in pieces, presented ion the surface of those cells, and can then be recognize by the immune system.
But what is very interesting with COVID is that in asymptomatically infected people - people who get infected but who don't develop the disease - these patterns on the surface of the antigen-presenting cell are recognized by NK cells. NK cells are innate immune cells - part of the innate immune system - that have the capability of recognizing molecular patterns that are extremely conserved - phylogenetically conserved patterns on the surface, for example of antigen presenting cells. These natural killer cells do not recognize, in contrast to, for example, the typical antibodies - also generated by vaccines or natural infection - those antibodies recognize a specific part of the virus, like the spike protein. In NK cells, they od not do this. They recognize molecular patterns that are shared among several different variants.
When you have an antigen-specific antibody - this antibody will recognize a very specific part of the virus. When we have a lot or variants that have another or a differetn contellation of this spike protein - then these antibodies will no longer recognize them or will only partially recognize them.
With NK cells, they don' tcare. The natural antibodies - the don't care. What they recognize is a molecular pattern on the surface of the pattern that is shared amongst several different variantts of covid, an dis even shared maong all coronaviruses.
So what happens? NK ccells get activated and at a very early sate og infection these patterns are expressed on the epithelial cells that are susceptible.
The virus infects the cell, as I was saying, enters into the cell, and immediatel yat an early stage of infection these patterns are presented and the NK cells have been mobilized and sensitized to recognize those patterns and they immediately kill the infected epithelial cell. This is the reason why asymptomatically people will be infected ,may spread the virus for maybe a week - definitely the concentration of the virus shed is certainyl not as high as in people who do get the disease and it is certainyl short lived. The virus gets eliminated after a few days. The infection gets completely abrogated. The virus gets kicked out and the asymptomatically infected person is completely free of virus. That is a different situation, of course, hten when you don't have these antibodies, or when these antibodies are only present in low quantities or in people who are not in good health. That is documented in the scientific literature.
It is proven that people who are not in good health have poor natural antibody prdouction and so they cannot drive the virus into this killing pathway. The virus is going in a direction that will cause severe disease, which is the most interesting situation for the virus. In asymptmatica the virus is shed for a short time in a local situation. But if you are symptomatic then you shed in high concentrations and for a long duration.
The only thing that is a little bit complicated, but so important to understand, what happens is that when people who are asymptomatically infected clear the virus, what we see is that all of a sudden a surge in antibodies. A surge in antibodies that is not extremely high the antibody levels rae not as high as in people who get sympatomatically infected and the surge is also short lived.
So what does that mean?? It means that after the infectiong ets cleared, people develop antiboides, but in 6 to 8 weeks these antibodies are no longer detectable.
Well taht is an interesting observation, but how does that go? What is the purpose of this? BEcause these antibodies dont' play any role in eliminating the virus.
The NK cells take care of this, and on top, these antibodies come at the point in tiem when the virus has already been elkinated. So it can't be thaot these antibodies are responsible for eliminating the virus.
Again, if you think that during thousands or millions of years of evolution, and coronaviruses being established in all sorts of mammalian populations - this is a phenomenon that must make sense. If it wouldn't have any significance, then evolution would not conserve it.
This is the poitn where I am saying, if you study this and you don't undestand what this means, then stop it. Or, do your homework and try to find out what is going on here. One thing is certain - this phenomenon got conserved through the co-evolution of the pathogen. Find out what the meaning is thereof.
What is the meaning? You have to realize that antibodies that are specific - for the spike prtoein fo r example - they have always a higher affinity for the spike protein then the natural antibodies. The natural antibodies, they recognize the virus as one antity - the antigen specific antibodies specifically recognize spike protein, so they have higher affinity for the spike protein.
So when it comes to binding to the spike protein, of course the specific antibodies will always have a higher affinity then the natura lantibodies.
Specific antibodies induced by vaccnation or infection - these are going to bind very strongly to the original virus. The original viral strain? The kind of strain that was initially responsiblef or the pandemic at the beginning. If now you have a variant - changes in the spike protein - doesn't look any longer exactly as the spike protein on the original virus - because these antibodies are very specific - they can no longer recognize the variants as well as they recognize the original virus. But, nevertheless, they still have a relatively high affinity for this virus because they are still directed to the S protein. And, even though they have lowe raffinity to the variants, they will still be able to out-compete the natural antibodies for binding to the very same virus.
So, what is important to notice here is that the natural antibodies, and this is key, they have a broad binding capacity. They can bind as well without any difference to the original virus, as to the variants. They recognize aptterns on the surface of the virus. Those molecular patterns are conserved. BUt their binding strenght is always lower for the spike protein than antibodies that are specifically directed against the spike protein, no matter whether they are directed against the original or the variants.
What does that mean? Well the spike protein is so important - it is responsible for the interaction with the receptor. The spike protein is responsible for the infectiousness of the virus. So variants have a higher binding strength to the receptor than the original virus, hence why these variants have higher infectiousness.
So what counts, in terms of antibodies is always the binding strength of the spike protein, because that matters in terms of infectiousness of the virus. If you have specific antibodies, they will, in terms of binding, out-compete the natural antibodies. So I was just saying that the natural antibodies are enable protection against all those variants.
Now, we will recapitulate a little bit because I was talking abotu 2 waves in a natural course of the pandemic. In the 2nd wave, The people who had good innate immunity - what happen s- they get infected, they go tinfected during the first wave no problem no disease - but they started to develop a short-lived surge in antibodies with relatively low affinity, short-lived, not high concentrations. Normally that isn't a problem unless, at that moment where they have the surge, they get re-infected - because at that moment with these short-lived antibodies, they will be facing a suppression of their natural antibodies - they are outcompeted/bypassed. When the natural immunity is disappear, the youngsters become susceptible. Because they cannot rely on these antibodies - certainly not if there are variants - because of the low affinity. They bind to teh spike, but this binding does not prevent variants from binding to the receptor on susceptible cells. This is because the binding is very strong. These are highly infectious with a changed S protein so that they can bind more strongly to the epithelial cells.
First way - people get infected, spreading, infectivity rate in the population is increasing - more virus. The likelihood that somebody who happens to have a short-lived surge of antibodies becomes re-infected. So they suppress their own natural innate immune response - increasing infectivity. At moment of infection - surge in antibodies - causing them to be open for re-infection.
This allows the wave of disease and death to shift to younger populations without any need for the virus to become more infectious. These people get ill, and natural asymptomatic carriers (NAC were asymptomatic during first infection of an earlier wave). They become more vulnerable because of lower innate immunity.
Not only young people, also people who have the lowest innate immunity. Suppression lowers capability of natural antibodies to intervene, but there are still a number of people with sufficient antibodies to be protected against all variants. The reservoir of young people who have potential for disease decreases as the virus spreads in a population. That's normally not a problem, because it becomes increasingly difficult because the remainder is still having very good innate immunity and the virus is looking "how can I move to another population", and it can because those people who got infected in the first wave start to have declining antibody titers, so the virus can without a problem go back to these members of the population and infect some of them, btu what happens here is that a lot of these people have seen the virus, so they're immune system can be re-activated with antigen-specific antibodies - immunological memory - they can immediately bombard the virus with a huge raise and concentration of antibodies.
People getting infected a second time come up with a surge of antibodies that will diminish the spread of the virus, and that's how we ultimately get to this herd immunity. So the question now is what happens if we are seeing that a lot of young people get infected, more of them get disease, because that is the place where the virus is now causing disease, who were perfectly healthy, who are now on ventilation, and they had no underlying disease, but they had suppression of their innate immunity because of short-lived antibodies. This is important to understand because if you now consider that we are now massively implementing infection-prevention measures, then we are giving the virus a difficult time. If you look at pandemics that have been well-documented, we've never seen that all of a sudden a whole series of highly infections strains pop up all over the place - all of a sudden, the variants show mutations that all converge on that S-protein which is responsible for their infectiousness. Connect this with the fact that we have been trying to prevent infectivity of the virus, so the virus do? The virus is going to select mutations in the spike protein that enable it to counter this affect of infection-prevention. That is how we see all tehse mutations in receptor-binding domain. So people will disagree with me about this.
Virus escapes through selective immune escape. It concentrates itself to enhance infectivity via the spike protein. There is almost a law in vaccinology. If you put a living organism, and especially a living organism that has a high capacity for mutation, if you put such an organism under immunological pressure while still leaving the door open for that organism to replicate, well for sure that organism is going to select mutations to overcome the pressure you have placed on it. It's the same thing with antimicrobials.
At what point do we have such a situation where there is immune pressure that is sub optimal? It is exactly at that stage that people who got infected during the first wave, will have a surge in antiodies that are not fully mature, are short-lived, don't reach high titers, that are not responsible for elimination of the virus - this is a sub-optimal immune response, and when the virus enters you have all the conditions for immune escape. A sub-optimal immune response tha gets confronted with the virus...