Cross-reactive natural immunity between bird flu and SARS2

So, as we see the first cases emerge of humans infected with bird flu, with mammals as an intermediary step, you may have found yourself wondering how the experience of the past four years will impact this development. Are people better prepared for the eventual jump into our species, thanks to our SARS2 experience? Or are we merely worse off, with immune systems that have been damaged?

To answer that question, we first have to look at what these two viruses have in common. Both are single-stranded RNA respiratory viruses. Both viruses have also developed a polybasic cleavage site, that allows them to infect endothelial cells (the cells lining your blood vessels), which they would normally not be able to do.

“Polybasic cleavage site” means these two viruses have a site right in the place where they bind to receptors (doors on our cells used to enter), that is composed of multiple basic (the opposite of acidic) amino acids (the building blocks of proteins). Such a site can attract enzymes, that have the effect of cutting the protein up into the right sized bits that allow it to do its job and take over the cell. This is why these polybasic cleavage sites often show the effect of allowing a virus to take over cell types it could otherwise not infect.

Under normal conditions in nature, such polybasic cleavage sites do not evolve, at least not in influenza. They look weird to the immune system, unlikely any chain of amino acids your own proteins contain. Birds that were infected by influenza with such a site and managed to survive it would be expected to develop antibodies that concentrate on this weird polybasic cleavage site (although such antibodies are insufficient on their own to prevent infection). As a result, they can still catch and transmit influenza, but they will be less likely to transmit influenza with a polybasic cleavage site anymore.

In nature, geese live for multiple decades, traveling around the world, getting infected by influenza, spreading influenza, developing immunity against it, then getting reinfected by other influenza strains that look different and transmitting those. In our chicken farms, the average life expectancy of a chicken is 42 days. In other words, our birds can not discriminate against these very deadly strains of influenza, as they die before they ever get reinfected.

Older wild birds on the other hand make sure that influenza stays a mild virus, both for their own species, as well as for mammals like humans. Our own elderly did the same job for us after the 1918 pandemic. They lived out the rest of their lives, with antibodies that specifically prohibit the 1918 virus from spreading, without really stopping other influenza viruses from spreading. Unfortunately for us, those elderly who had such excellent immunity have died by now.

Your body has a wide range of different tools that it uses to protect itself from viruses. The big divide is between adaptive immunity (which includes the antibodies) and innate immunity. With inactivated vaccines, not based on a live virus capable of actually infecting cells, we mainly stimulate adaptive immunity. This has resulted in the situation in which people who were vaccinated against SARS-COV-2, rely more on antibodies to deal with future infections from that virus, than people who were not vaccinated against it. You can see this difference reveal itself whenever you compare vaccinated and unvaccinated people’s response to new strains of that virus.

Here you see antibodies in unvaccinated adults against SARS2:

Here you can see the response in vaccinated adults, who received two shots of mRNA:

You can see that vaccinated adults have some neutralizing antibodies that are on stand-by against the virus, that also bind to the newest versions of the virus. The adaptive immune system has simply taken on a bigger role in preventing reinfections in vaccinated people, than it has in unvaccinated people.

Natural immunity against SARS2 is not a free lunch, it would be dishonest for me to argue that. What I have always argued instead, is that it results in a better outcome for people in the long run, that is, over a period of multiple years. It means that endothelial cells will be infected. This means surrounding endothelial cells will respond by going on high alert, along with the infected endothelial cells (if they survive it). Studies suggest an increased risk of cardiovascular events after a SARS2 infection, particularly among the unvaccinated. That risk is of course concentrated among people who already had poor cardiovascular health.

But what I have always said, is that humans settled on deploying the wrong tool for the job, which will reveal its impact in the long run. They are forcing people’s bodies, to deploy a lot of adaptive immune capacity, against a single respiratory virus. This comes at the cost of their lungs ability to deal with other respiratory viruses. That’s why you can see a gradual rise in respiratory problems in the Dutch population, as growing numbers of people go to their doctor, complaining of a cough that just won’t go away:

Whether we will see a sudden unexpected failure of the adaptive immune response against SARS2, because of a sudden mutation to the virus, is something that is hard to predict. I have explained some mechanisms through which this could suddenly happen here.

But I want to answer instead, what this experience will mean for the eventual bird flu pandemic our species will have to face.

It has been known for a long time, that exposure to unrelated respiratory viruses, can help dampen influenza pandemics. The 1918 influenza pandemic had the worst impact on isolated islands in the Pacific. Whereas on Hawaii just 0.4% of the population died, on Samoa 22% died.

In the above image you can see why this is. Alveolar macrophages are altered by the experience, memory NK cells establish themselves in the lungs (which I have told you about many times before). On the other hand, in isolated communities, a whole bunch of influenza specific T-cells are deployed against the 1918 flu, that suddenly trigger a very aggressive immune response, damaging the lungs and thereby allowing bacteria to join the party too.

The body does not depend on T cells and B cells, to learn from previous respiratory infections. There are also alterations to lymphatic and vascular tissues. Tissues that were under severe stress in a previous infection, will have alterations that help them cope with future infections, similar to how muscles under stress during exercise get better vascular system to help them cope with future exercise.

Some people tell you that your body does not learn from viral infections. Those people are wrong.

The endothelial cells that are infected by both SARS2 and by bird flu, can effectively be thought of as immune cells in their own right. They are equipped with a wide range of innate immune tools. When they are infected by an RNA virus, they will learn to produce the sort of receptors within the cell, that allows a cell to check whether there’s a big chunk of strange RNA and deletes that RNA when necessary. These responses are recalled more rapidly next time they’re dealing with a virus.

Most important of all perhaps are the NK cells, that have migrated into the tissues where SARS2 showed up, at least in people who were infected before ever being vaccinated against SARS2. Those NK cells have receptors that allow them to recognize whether a cell is sick or healthy. They use those receptors, in combination with specific receptors that recognize the sort of proteins covered in sugar molecules, that viruses use to enter cells. Importantly, we know that the exact same receptors the NK cells use for influenza, are the ones they use for SARS2: NKp44 and NKp46 among others.

When NK cells see the same virus again in a cell, they are less aggressive against it: They prefer to release interferon Gamma, to let the cell solve it on its own, rather than killing the cell. On the other hand, when they see a different virus in a cell, they tend to be cautious again and kill the cell. This makes perfect sense of course, when you think about it.

Unfortunately, this has to be contrasted with adaptive immunity. The antibodies produced by the B cells and plasma cells in response to SARS2, are useful against SARS2. Some of those antibodies may bind to influenza too, but they’re not going to be very useful against it. Often they bind to a place on SARS2 that neutralizes the virus, but bind to a place on influenza where it doesn’t neutralize influenza. To make matters worse, these antibodies can then prevent the immune system from deploying a response against influenza that does work. They can even prevent an NK cell from recognizing what’s going on.

This matters a lot, because whereas most people are vaccinated against measles or polio and then never encounter these viruses during their lives, people who were vaccinated against SARS2 are constantly getting infected by different versions of SARS2, that force more and more T cells and B cells to populate their tissues to focus on this particular virus. This adaptive immune response interferes in the response to unrelated viruses, like Dengue.

For SARS2 to overcome the adaptive immune response induced by these vaccines, it needs a lucky monster: A strain that is radically different from the currently circulating strains. It’s hard to predict when and if that will happen, but it can happen very suddenly.

Unfortunately, for bird flu that’s just not true. Once it jumps into our species, it will inherently look very different, most of the T cells and B cells people’s bodies deployed against SARS2 will be of little use to it. Rather, they will be interfering in developing a proper response to bird flu.

If bird flu could immediately jump from birds into humans and spread through our species, we would have probably already seen that happen by now. Instead, it seems that it first needs to use another mammal, as an intermediary state before the big jump.

I’m not a genius with a crystal ball, I can’t tell you whether we’ll have bird flu pandemic a month from now, a year from now or a decade from now. But I can read studies. Those studies very clearly demonstrate: Natural infections with unrelated respiratory pathogens protect people against severe influenza viruses.

In contrast, an adaptive immune response, induced by multiple breakthrough infections after vaccination with inactive vaccines against a particular respiratory infection, has no such effect. Rather, it increases vulnerability to unrelated pathogens. People’s lungs are now filled with T cells and B cells, that are trying desperately to keep out SARS2.

That’s not my theory. It’s not Geert van den Bossche’s theory either. It’s simply what humanity knows, from the numerous studies that have been done on this subject.

We live in the pandemic era. That’s the logical consequence, of a number of things:

-Climate change forcing animals in contact that would normally never meet each other.

-Human overpopulation.

-Many millions of immunocompromised people kept alive with various therapies.

-Humans traveling around the world in airplanes, that can put you from London in Brazzaville within hours, a journey that would take our ancestors weeks.

-Human factory farms, full of inbred animals.

-The stupid decision to vaccinate the chickens in the factory farms against influenza.

Vaccinating people of all age categories with these inactivated vaccines, against a respiratory virus (SARS2) that killed less than 1% of people it infected, almost all elderly in poor health, is a luxury humanity could not afford. Yet they decided to do it anyway.

It did not work, it caused constant reinfections with waves of more infectious variants of the virus. The fortunate side-effect of that, is that unvaccinated people in good health have built up competent immunity that will help protect them against the bird flu pandemic.

We spent our ammunition on the wrong bug. We went into the woods at night and emptied our gun on a wolf, not realizing the bear approaching us from the back.