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The good part about ‘waning’ immunity

In early March, Deepta Bhattacharya, an immunologist at the University of Arizona, celebrated a milestone: reaching the point of full vaccination two weeks after receiving his second Pfizer recording. Since then, he has seen the number of antibodies against the coronavirus in his blood slowly but surely decrease.

The drop wasn’t abrupt, but it’s definitely happening — regular checkups have shown his antibody levels, known as titers, drop from spring through summer and now into fall. The slump fits in with the story where countless reports have been sounding alarm bells for some time: in the months after vaccination, our antibodies are peace out, a trend often described as a “decreasing” by immunity, and proof that we all urgently need reinforcements to fortify our defenses.

It all sounds, frankly, like a tragedy. But as Bhattacharya and others assured me, it really, really isn’t. “All we hear about is titers,” said Stephanie Langel, an immunologist at Duke University. That fixation “misses a whole nuance”.“Antibodies are” supposed become extinct; that’s why they always do. Still, even if our antibodies decline in absolute terms amount of, these scrappy molecules improve their quality, continue to replace itself with new versions that remain improve their ability to get the virus under control. Months after vaccination, the average antibody found in the blood simply has a higher defensive appearance. “That’s why I hate the word” diminishingJennifer Gommerman, an immunologist at the University of Toronto, told me. “The antibody levels are declining, but something good is also happening: the immune response is evolving.”

The focus on antibody count alone actually does a disservice to our understanding of immunity, experts told me. Like a block of wood cut into a sharper blade, vaccinated immune systems can hone their skills over time. Part of diminishing certainly means: less. But it can also mean better.

A few weeks after vaccination, a group of immune defenders called B cells begins to massively pump out antibodies. But many of these early antibodies, as Bhattacharya told me, are “really worthless” in their work. Their raison d’être is to be sticky — the Y-shaped molecules hook their ends onto a specific piece of SARS-CoV-2’s anatomy and stick around for life. The better they are at glomming, the more likely they are to avert the threat. Sometimes it’s a solo act: Only antibodies can take hold so tightly that they prevent the virus from entering a cell, a process called neutralization. Or they use the stems of their Y’s to defeat other members of the immune system in a destructive aid.

But that’s the best-case scenario. Most of our B cells, or the antibodies they produce, don’t respond at all to SARS-CoV-2, or any vaccine that looks like it. That’s because our bodies are always randomly producing B cells, repeatedly mess with their genetics so that they will make a diverse set of antibodies –billions or trillions in total— who collectively can recognize just about every microbe they could ever see. However, this process is random and imprecise: When B cells are born, “they don’t have a specific pathogen in mind,” Gabriel Victora, an immunologist at Rockefeller University, told me. Rather than clinging tightly to the surface of the virus, many antibodies can simply “bounce on and off,” giving the pathogen plenty of time to tear itself free, Bhattacharya said. It’s the best defense the body can beat in the short term, as it has never encountered the bug before. Early antibodies are kind of the best of the immune system guesses on defense – the immunological equivalent of throwing spaghetti against a wall to see what sticks – which usually means we need a lot of it to really hold the pathogen in place. They are also vulnerable. Most antibodies don’t linger for more than a few weeks before breaking down.

Such thin fighters are not very good long-term investments. So as the undersized antibodies fight it out on the front lines, the immune system will send a contingent of young B cells to a training camp, called a germinal center, where they can delve into the coronavirus. What is happening in these training camps is a miniature royal battle as the cells crowd and struggle desperately for access to the resources they need to survive. Their weapons are their antibodies, which they brandish frantically in an attempt to cling to chunks of dead coronavirus while a panel of other immune cells assess them from afar. Only the most combative among them – those whose antibodies are most firmly entrenched in the coronavirus – advance to the next round, and the losers die in defeat. As Gommerman put it, “If they suck, they die.”

The harrowing cycle repeats itself over and over and only gets more grim. Surviving B cells will xerox themselves and intentionally introduce errors into their genetic codes in the hopes that some of the mutations will increase their antibodies’ chance of attaching themselves to the virus. The whole process is downright “Darwinian,” like a super-accelerated form of natural selection, Victora said. The weak are wiped out, leaving only the sharpest and strongest. It’s bad too long lasting. Researchers such as Ali Ellebedy, of Washington University in St. Louis, have found that these cull tournaments are still at least 12 to 15 weeks after people get their COVID-19 vaccine, maybe longer.

When this all gets a little too much squid game, consider the much brighter result: at the end of this process, our bodies are left with some truly primo antibodies, well poised to take on the mantle of protection as the first waves of mediocre defenders begin to fall away. Here’s what happens in the immune systems of those vaccinated months ago: an initial burst of antibody activity, followed by a gradual decline, as the body returns to baseline. “Immune reactions can’t stay in your blood forever,” Langel told me. If they didn’t decrease, we wouldn’t have room or resources for the body to mount another defense, against another threat — and our blood would be nothing more than a useless antibody sludge.

There’s another way to think about the dip in antibodies after vaccination: taking out the trash. Early-acting B cells are so messy in some cases that they’re not that worth keeping around. Evolution has also discovered the benefits of this pattern, which is perhaps why the B-cell victors are not only of higher quality, but also last much longer. While the first B cells to collect after vaccination may only live for a few days, the cohort that beat their peers in training can remain in the bone marrow or blood for months or years. Some will continue to squeeze out antibodies for the long haul, while others wander in silence, ready to resume their defensive duties when called upon again. “What’s seen as a ‘loss’ of antibodies is actually the slow decline of the lesser, transient response,” Victora told me. And when antibodies are needed, such as when the actual virus infects us, veteran B cells shall they produce again, in gigantic quantities. Antibodies themselves don’t always stick around. But the ability to create them usually does.

There is definitely a limit to how much quality can outweigh quantity – one antibody, no matter how bad, can’t do the job of hundreds. Experts don’t yet know how many antibodies (good, meh, or “crappy”) people must have in tow to be considered well-protected against COVID. Rishi Goel, an immunologist at the University of Pennsylvania, told me that his work has shown that six months after vaccination, the number of neutralizing antibodies in human blood decreases noticeable from its peak. But he and others have also discovered that there are small difference in how much neutralization? the body can– a strong indication that superior antibodies have since come to the plate. Again, antibody levels always drop. That does not mean that the immune protection (which is about more than just antibodies) disappears.

The slow trudge toward self-improvement can also be a reason not to rush into a booster shot. Boosting reminds the immune system of a threat it has seen before. But offering that refresher too often or too soon can be pointless, even somewhat counterproductive, if active germination centers are still doing their thing. Waiting a little longer can help ensure that the best possible B cells are revived to make new antibodies. So immunity is much less about what’s around now, and more about what’s nearby when it is needed; it’s okay if those defenses aren’t always visible, as long as they spring back into action when called forward.

All this means that a delay in the production of antibodies can be seen in a sense as: comforting. It’s a sign of an immune system allocating its resources wisely, rather than constantly panicking itself. Bhattacharya, for instance, isn’t at all impressed with what’s happening to his antibodies, which, nearly eight months later, still look pretty damn good despite the numerical dips — because they still seem to exorcise the virus when he puts them on. test in his lab. According to Langel, that is standard. When she sees that the antibodies ‘decrease’, she shrugs. “I say, ‘Look,'” she told me, “‘that’s the immune system, doing what it does.'”