Immunity to COVID-19 could last longer than you'd think

All around the world, there seem to be signs that immunity to SARS-CoV-2, the coronavirus that causes the disease COVID-19, doesn't last very long after you're vaccinated.

Israel is now having one of the world's worst COVID-19 surges about five months after vaccinating a majority of its population. And in the U.S., health officials are recommending a booster shot eight months after the original vaccine course.

So, how long does immunity last after two doses of the vaccine? Six months or so? And at that point, how much protection is left over?

It all depends on which type of immunity you're talking about, says immunologist Ali Ellebedy at Washington University in St. Louis. Six months after your vaccine, your body may be more ready to fight off the coronavirus than you might think.

"If you were vaccinated six months ago, your immune system has been training for six months — you are better ready to fight a COVID-19 infection," says Ellebedy.

A series of new studies, including two led by Ellebedy, suggests that mRNA vaccines like those from Pfizer-BioNTech and Moderna trigger the immune system to establish long-term protection against severe COVID-19 — protection that likely will last several years or even longer, Ellebedy says.

To understand what he's talking about, let's say you received the second Moderna or Pfizer vaccine six months ago. Right away, your immune system got to work and began making antibodies.

These antibodies are a bit like archers outside the moat of a castle. They set up in the lining of your nose and throat, ready to shoot down (aka neutralize) any SARS-CoV-2 particles that try to enter the moat (aka your nasal tissue).

These antibodies can prevent an infection, says bioimmunologist Deepta Bhattacharya at the University of Arizona. They stop the virus from entering cells and setting up shop. They are the body's front-line defense.

But right after vaccination, this initial round of antibodies has a few problems. The antibodies are a bit wimpy. They're not that well trained at killing SARS-CoV-2, and they're not very durable, Bhattacharya says.

About a month after the second mRNA shot, the number of antibodies in the blood reaches its peak level and then starts to decline. The antibodies themselves degrade and the cells that make them die, a study published in the journal Nature reported in June.

This happens with every vaccine, whether it's for COVID-19, the flu or measles, Bhattacharya says. "In every single immune response, there is a sharp rise in antibodies, a period of sharp decline, and then it starts to settle into a more stable nadir."

Some news articles have largely focused on this decline of antibodies as the cause of "waning immunity." And it's true, Bhattacharya says, that this decline in antibodies, combined with the high potency of the delta variant, which began dominating many countries this year, is likely increasing the rate of infection in fully vaccinated people.

"If you get a big dose of delta, as the variant often gives, the virus can slip past the initial wall of antibodies," he says. "So I think we may be seeing some signs of that. But the [level of breakthrough infections] is probably not as dramatic as I think it's being made out to be."

Why? Because many media organizations have largely overlooked several key facts about the antibodies present eight months after the vaccine. For starters, they're more powerful than the original ones triggered by the vaccine, Bhattacharya says.

While the first round of archers (antibodies) was out guarding the moat of your castle (respiratory tract), the immune system wasn't just sitting around idly, hoping those soldiers would be enough. Instead, it was busy training better archers — and a whole bunch of foot soldiers too.

After your second shot, the immune system sets up a training center in the lymph nodes to teach special cells how to make more powerful antibodies, the Nature paper from June reported.

"The quality of the antibody improves over time. It takes far fewer of those new antibodies to protect you," Bhattacharya says. "So I think that worrying about antibody decline is not something that's productive," he adds.

At the same time, the cells that make these souped-up antibodies become souped up themselves, he adds. In the training center, they learn how to make a huge amount of the highly powerful antibodies.

"These cells are remarkable," Bhattacharya says. "They're estimated to spit out something like 10,000 antibody molecules per second." So you don't need many of these cells to protect you against a future infection.

"We've done some back-of-the-envelope calculations to figure out how many of these cells are needed to protect a mouse from a lethal infection. It's three," Bhattacharya says. "Of course, we're bigger than mice. But you get the sense that it doesn't take many to offer good protection."

On top of that, these cells learn something remarkable in the training center: how to persist. "They're essentially given the gift of eternity," says immunologist Ellebedy.

He and his colleagues have found that by about six months after vaccination, these antibody-producing cells go into the bone marrow, where they can live for decades, perhaps even a lifetime, studies have found, and continue to produce antibodies the entire time. In one 2008 study, researchers identified antibodies that could neutralize the 1918 flu in the blood of people who were exposed to the virus 90 years earlier.

"We looked in the bone marrow and have seen these cells in people previously infected with SARS-CoV-2," Ellebedy says. "Now we are finishing research that shows these cells appear in the bone marrow after vaccination as well."

Called long-lived plasma cells, these cells will likely pump out antibodies into the blood for decades, Ellebedy says, giving people some sustained, long-term protection against SARS-CoV-2. (There is a caveat: If the virus changes too much, these antibodies won't be as effective.)

"The antibodies are maintained at very low levels, but they're the first line of defense against an infection," Ellebedy says. "If you're taken by surprise by SARS-CoV-2, these antibodies will slow down the replication of the virus" — until reinforcements come along.

And reinforcements will likely come!

On top of training up better archers (antibodies) and factories to create them (plasma cells), the immune system has also been training up the equivalent of foot soldiers, several studies have found. These foot soldiers are called memory B cells and memory T cells, and they largely serve as a surveillance system, looking for other cells infected with SARS-CoV-2.

"They're patrolling all over," Ellebedy says, checking to see if a cell has SARS-CoV-2 hiding in it. "It's almost like going through the neighborhood, house by house, and just making sure it's clean."

These foot soldiers can't prevent an infection from initially occurring, but they can quickly stop one once it occurs, says immunologist Jennifer Gommerman at the University of Toronto. "Because of the vaccine-generated 'memory' of the SARS-CoV-2 spike protein, you get a very brisk cellular immune response."

OK. So now we've got all the information to understand what's going on with the COVID-19 vaccine and immune durability.

About six months after the shots, the antibodies in the blood have fallen — as expected. They're also a bit less effective against the delta variant. "Together, that means there are more symptomatic infections as we go further out from the vaccination rollout," Gommerman says.

But in vaccinated people, these infections will most likely be mild or moderate because the immune system isn't starting from scratch. In fact, it's the opposite. It has been training cells and antibodies for months.

"You still have all this immunity inside of your body that will then say, 'OK, we've had a breach, and it's time to bring in the cellular immunity and respond to this threat,' " Gommerman says. "And because of vaccination, you have cells that can do that really quickly."

And so, overall, you'll be less sick than if you weren't vaccinated and be much less likely to end up in the hospital, she says.

"That's really what the vaccines were designed to do — to teach the immune system to deal with this invader if an infection does occur," Gommerman says. "And the vaccines do that remarkably well."

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