With so much information – and misinformation – around the COVID-19 pandemic, it can be easy to get overwhelmed. “COVID-19 will likely be with us forever,” reads one headline, while another tells us that eradication of the virus is possible. Booster shots are counterproductive and selfish, but also might become an annual tradition. And on top of all that, there’s the constant barrage of memes, rappers, and good old-fashioned innocent misunderstandings that tell us – against medical and scientific advice – not to get vaccinated.
One reason it can all get confusing is simply because COVID-19 is such a new illness – we don’t know as much about it as other diseases, because we simply haven’t had enough time to study it long-term. But now we’re a couple of years into the pandemic, there’s a new term entering the discourse: antibodies, you may have heard, are “waning”.
Some people have even gone so far as to suggest that vaccination is pointless because of it – something that, if true, would probably deserve to be on every news channel across the country. After all, the government spent billions on these shots – what a waste that would be if they simply ran out of juice after a while. So, is it true – do our antibodies from vaccinations really “wane”?
But here’s the thing: that happens with every vaccine. In fact, it’s kind of the whole point.
“Things wane,” explained Nicole Doria-Rose, an immunologist at the US National Institute of Allergy and Infectious Diseases, in Nature. The fact that our antibody levels are sky-high after a vaccine and then taper off over the next few months is just “how vaccines work.”
To understand why, we need to take a closer look at how the immune system works.
When a pathogen gets into the body, the first immune cells to step up and face the challenger come from the innate immune system – the part of the immune system we’re born with. The innate cells are kind of like the droids in Star Wars – they’re always alert, always ready to rush into a fight, and frankly, not very likely to make it to the end of the movie in one piece.
After the innate cells have fended the pathogen off as best they can, in steps the adaptive immune system – the bit that grows and changes throughout our lives as we are exposed to various germs and viruses. The big hitters in this category are B cells and T cells: the former are responsible for antibody production to guard our cells against infection; the latter go one step further by seeking out already-infected cells and forcing them to self-destruct.
Should a pathogen make it past the innate immune cells, then, it’s the B cells and their antibody arsenals next. Now, these cells are smarter than the innate immune cells – they work using intel from their ill-fated innate brethren to tailor antibodies to the pathogen, for instance. However, they’re not that much smarter, at least not at first: a whole bunch of the first squadrons of antibodies are “really crappy” at their job, University of Arizona immunologist Deepta Bhattacharya told The Atlantic. They are sent out into the world with one objective: find pathogen cells, grab them, and don’t let go – yet many just “bounce on and off,” he explained.
That’s why antibody levels immediately after vaccinations are so high: our bodies are basically playing the law of averages. Throw everything you have that might work at the new invader, our B cells decide, and something is bound to stick. The antibodies that do stick, we can make more of, and the antibodies that don’t – well, they won’t stick around for long.
It can take up to three or four months of cut-throat natural selection for our immune systems to weed out the weaklings from those first antibodies, and sure, that can give the impression of our immunity “waning” as our antibody levels drop. However, the antibodies and white blood cells that survive the vaccination boot camp come out stronger and smarter than before.
And here’s the good news: our antibodies may be waning, but our immunity probably isn’t.
“What is seen as a ‘loss’ in antibodies is actually the slow waning of the less-good, short-lived response,” Gabriel Victora, an immunologist at Rockefeller University, told The Atlantic. Think of it like an immune system karate tournament (or even better, fat bear week): as time goes on and fights are won or lost, the number of competitors goes down – but the ones left are really, really good.
“That’s why I hate the word waning,” explained Jennifer Gommerman, an immunologist at the University of Toronto, also speaking to The Atlantic. “Antibody levels are declining, but something good is happening too: The immune response is evolving.”
There’s a good reason immunologists caution against putting too much emphasis on antibody counts. The little Y-shaped proteins are definitely important parts of the body’s defense system, but they’re not the only part – and “constantly measuring the level of antibodies in your blood isn’t what will tell you if you are protected or not,” said Natália Pasternak, head of the Question of Science Institute, in The Guardian last month.
“What will tell you if you are protected or not is if you have memory cells [and] a sufficient cellular response,” she explained. “You don’t measure this with a simple antibody test.”
And by that measure, vaccines – and our immune systems – seem to be doing their jobs. Six months after vaccination with an mRNA (i.e. Pfizer or Moderna) shot, our bodies have more memory B and T cells than ever. When it comes to long-term immunity, that’s a better metric than raw antibody numbers: these B and T cells are specialized white blood cells that hang out in the bone marrow and thymus, keeping an eye out for the specific viruses they’ve been trained against. If a stray pathogen happens to wander in, even decades later, these cells can mount an immediate search-and-destroy operation to wipe it out.
"You have this reserve,” University of Pennsylvania immunologist John Wherry, lead author on a recent study into long-term immunity against COVID-19, told Nature. “Circulating antibodies may be declining, but your immune system is capable of jumping into action once again.”
If the memory B and T cells are the immune system’s elite snipers, antibodies are more like its untrained infantry troops: sure, having a gazillion of them is probably an advantage overall, but there’s going to be quite a few who don’t know what they’re doing, and any direct hits on the enemy are likely as not going to be coincidental. In the long term, in other words, they’re not what a successful defense campaign should be relying on – maintaining those high levels of antibodies, Bhattacharya told The Atlantic, “would require so much energy – I don’t even know where you’d keep all those cells.”
This hits at an important point when it comes to using antibody levels as a judge of immunity: in the absence of any virus cells, your antibody levels will be low even if your body is well protected.
“From an immunological standpoint, plasma neutralising antibody titres [effective concentrations] are expected to decay eventually following vaccination,” explained epidemiologists Jake Scott, Aaron Richterman and Muge Cevik in an editorial for the BMJ. “But robust and long lived plasmablast and germinal B cell responses have been shown after mRNA vaccination, and memory B cells have been shown to increase over at least six months, improve functionally, and provide cross-variant protection.”
In other words, those initial waves of antibodies that our body sends out after vaccination? Experts expected them to wane – they always do. “Cellular immunity is what’s going to protect you from disease,” explained immunologist Jennifer Gommerman in Nature: those memory B cells trained by vaccination to build the best possible antibodies as soon as they spot a stray COVID-19 virus particle, and the memory T cells that can take care of cells which are already infected.
So what does this mean for booster shots? One tentative estimate from July put the vaccine-induced immunity period for COVID-19 at around one or two years, meaning booster shots may become a regular necessity. Indeed, some richer countries like the UK and USA are already prepared for nationwide booster shot rollouts.
However, some experts think the arguments for boosters are still shaky, regardless of any “waning antibodies”. That’s partly because of the huge lingering disparity between richer and poorer countries’ vaccine access – “In my view,” evolutionary epidemiologist Katrina Lythgoe told Nature, “apart from people who are particularly vulnerable, efforts should be directed to getting people, globally, vaccinated.”
It’s also because the numbers on the supposedly declining immunity levels just, well, aren’t that bad. It’s true that the number of breakthrough cases – people getting sick with COVID-19 despite being fully vaccinated – are on the rise, but that’s in a large part just because so many people are vaccinated now. A better thing to look at is how severe those breakthrough cases are compared to cases in unvaccinated people – and there, the evidence is compelling. One study, published in the New England Journal of Medicine in July, found that breakthrough cases were less likely to come with a fever, were less severe, and lasted a shorter time overall.
“We gave these vaccines to some of the highest risk groups in this country – doctors, nurses, and first responders,” study co-author Sarang Yoon explained in a statement. “These are the people who are getting exposure to the virus day in and day out, and the vaccine protected them against getting the disease. Those who unfortunately got COVID-19 despite being vaccinated were still better off than those who didn’t.”
Now, nobody’s saying we know everything about how COVID-19 immunity is going to play out in the long-term – “We’re on new territory here,” explained immunologist Andrew Read in Nature. But so far, vaccines are holding out: some of the benefits may have been slightly “eroded,” he said, as the virus has evolved, but tweaks in vaccine design have been able to counter that.
When we see antibodies “waning”, we shouldn’t necessarily panic: “that’s the immune system, doing what it does,” immunologist Stephanie Langel told The Atlantic. And while “waning (neutralizing) antibody levels in patients previously infected with SARS-CoV-2 might render them susceptible to reinfection again,” vaccinologist Benjamin Meyer wrote in a commentary article for The Lancet, “the induction of a robust memory immune response makes it entirely plausible that the majority of these patients are still protected from severe COVID-19 disease.”
So are “waning antibodies” a thing after vaccination? Yes, absolutely. But does it mean vaccines are useless or ineffective? Absolutely not – it’s not a sign that vaccines are failing us, it’s a sign they’re doing their job.
“Yes, we should be concerned,” immunologist Ali Ellebedy told The Atlantic. “But I think we should also be optimistic.”
“Over time, our antibodies just become better.”