Some scientists have called it "superhuman immunity" or "bulletproof." But immunologist Shane Crotty prefers "hybrid immunity."
"Overall, hybrid immunity to SARS-CoV-2 appears to be impressively potent," Crotty wrote in commentary in Science back in June.
No matter what you call it, this type of immunity offers much-needed good news in what seems like an endless array of bad news regarding COVID-19.
Over the past several months, a series of studies has found that some people mount an extraordinarily powerful immune response against SARS-CoV-2, the coronavirus that causes the disease COVID-19. Their bodies produce very high levels of antibodies, but they also make antibodies with great flexibility — likely capable of fighting off the coronavirus variants circulating in the world but also likely effective against variants that may emerge in the future.
"One could reasonably predict that these people will be quite well protected against most — and perhaps all of — the SARS-CoV-2 variants that we are likely to see in the foreseeable future," says Paul Bieniasz, a virologist at Rockefeller University who helped lead several of the studies.
In a study published online last month, Bieniasz and his colleagues found antibodies in these individuals that can strongly neutralize the six variants of concern tested, including delta and beta, as well as several other viruses related to SARS-CoV-2, including one in bats, two in pangolins and the one that caused the first coronavirus pandemic, SARS-CoV-1.
"This is being a bit more speculative, but I would also suspect that they would have some degree of protection against the SARS-like viruses that have yet to infect humans," Bieniasz says.
So who is capable of mounting this "superhuman" or "hybrid" immune response?
People who have had a "hybrid" exposure to the virus. Specifically, they were infected with the coronavirus in 2020 and then immunized with mRNA vaccines this year. "Those people have amazing responses to the vaccine," says virologist Theodora Hatziioannou at Rockefeller University, who also helped lead several of the studies. "I think they are in the best position to fight the virus. The antibodies in these people's blood can even neutralize SARS-CoV-1, the first coronavirus, which emerged 20 years ago. That virus is very, very different from SARS-CoV-2."
In fact, these antibodies were even able to deactivate a virus engineered, on purpose, to be highly resistant to neutralization. This virus contained 20 mutations that are known to prevent SARS-CoV-2 antibodies from binding to it. Antibodies from people who were only vaccinated or who only had prior coronavirus infections were essentially useless against this mutant virus. But antibodies in people with the "hybrid immunity" could neutralize it.
These findings show how powerful the mRNA vaccines can be in people with prior exposure to SARS-CoV-2, she says. "There's a lot of research now focused on finding a pan-coronavirus vaccine that would protect against all future variants. Our findings tell you that we already have it.
"But there's a catch, right?" she adds: You first need to be sick with COVID-19. "After natural infections, the antibodies seem to evolve and become not only more potent but also broader. They become more resistant to mutations within the [virus]."
Hatziioannou and colleagues don't know if everyone who has had COVID-19 and then an mRNA vaccine will have such a remarkable immune response. "We've only studied the phenomena with a few patients because it's extremely laborious and difficult research to do," she says.
But she suspects it's quite common. "With every single one of the patients we studied, we saw the same thing." The study reports data on 14 patients.
Several other studies support her hypothesis — and buttress the idea that exposure to both a coronavirus and an mRNA vaccine triggers an exceptionally powerful immune response. In one study, published last month in The New England Journal of Medicine, scientists analyzed antibodies generated by people who had been infected with the original SARS virus — SARS-CoV-1 — back in 2002 or 2003 and who then received an mRNA vaccine this year.
Remarkably, these people also produced high levels of antibodies and — it's worth reiterating this point from a few paragraphs above — antibodies that could neutralize a whole range of variants and SARS-like viruses.
Now, of course, there are so many remaining questions. For example, what if you catch COVID-19 after you're vaccinated? Or can a person who hasn't been infected with the coronavirus mount a "superhuman" response if the person receives a third dose of a vaccine as a booster?
Hatziioannou says she can't answer either of those questions yet. "I'm pretty certain that a third shot will help a person's antibodies evolve even further, and perhaps they will acquire some breadth [or flexibility], but whether they will ever manage to get the breadth that you see following natural infection, that's unclear."
Immunologist John Wherry, at the University of Pennsylvania, is a bit more hopeful. "In our research, we already see some of this antibody evolution happening in people who are just vaccinated," he says, "although it probably happens faster in people who have been infected."
In a recent study, published online in late August, Wherry and his colleagues showed that, over time, people who have had only two doses of the vaccine (and no prior infection) start to make more flexible antibodies — antibodies that can better recognize many of the variants of concern.
So a third dose of the vaccine would presumably give those antibodies a boost and push the evolution of the antibodies further, Wherry says. So a person will be better equipped to fight off whatever variant the virus puts out there next.
"Based on all these findings, it looks like the immune system is eventually going to have the edge over this virus," says Bieniasz, of Rockefeller University. "And if we're lucky, SARS-CoV-2 will eventually fall into that category of viruses that gives us only a mild cold."
The original caption for this story stated: "An illustration of antibodies attacking a coronavirus particle." When antibodies attack, they aim the y-shaped appendage at the viral particle.
RACHEL MARTIN, HOST:
Researchers have identified a category of people who generate an exceptionally strong immune response to vaccines. Some scientists are calling it superhuman immunity. Here's NPR's Michaeleen Doucleff.
MICHAELEEN DOUCLEFF, BYLINE: For the past year and a half, Theodora Hatziioannou has been pushing the limits of what's possible in immunology.
THEODORA HATZIIOANNOU: No other virus has been studied to this extent. And no immune responses to a single virus have been studied in such detail in real time.
DOUCLEFF: Hatziioannou is a virologist at Rockefeller University. She's been following with excruciating detail how the immune system learns to protect a person from COVID - specifically, what happens to individual antibodies in people's blood after exposure.
HATZIIOANNOU: It's extremely laborious work, and it's extremely difficult to do. You can't do it with a lot of patients.
DOUCLEFF: But earlier this year, Hatziioannou started to notice something quite remarkable - some people mount this exceptionally potent response to mRNA vaccines.
HATZIIOANNOU: Those people have amazing responses.
DOUCLEFF: She says they generate high levels of antibodies. But that's not what's key here. Instead, it's about the type of antibodies. They're more powerful, more flexible, more diverse. They not only recognize and kill the original version of SARS-coV-2, but also all the variants they tested, including delta. And the antibodies don't stop there. They can also kill other SARS-like like viruses, ones found in bats and penguins.
HATZIIOANNOU: These people even neutralize SARS-coV, the first coronavirus that came 20 years ago, which is very, very different.
DOUCLEFF: Hatziioannou and her colleagues published these findings in the journals Nature and Immunity. So just who is capable of mounting this so-called superhuman immune response?
PAUL BIENIASZ: Individuals who were infected early in the pandemic and then sort of between six and 12 months later, they were then vaccinated.
DOUCLEFF: That's Paul Bieniasz. He's also at Rockefeller University and helped to lead these studies. He's talking about people who got sick last year and then received a Pfizer or Moderna vaccine this year. Bieniasz says that the natural infection is critical to this immunity because the virus may stick around in the body long after exposure.
BIENIASZ: While SARS-coV-2 infection itself is thought to be quite short-lived, it is likely that some viral proteins and possibly even some infected cells persist, perhaps even for months.
DOUCLEFF: This may give the immune system extra time to optimize and diversify its antibodies, so the antibodies can recognize all sorts of variants. Then upon vaccination, these antibodies get boosted to a high level.
BIENIASZ: One could reasonably predict that these individuals would be quite well-protected against most and perhaps all of the SARS-coV-2 variants that we are likely to see in the foreseeable future.
DOUCLEFF: On the surface, this seems to suggest some bad news - that you need to catch COVID to have this super immunity. But John Wherry at the University of Pennsylvania says that's probably not the case.
JOHN WHERRY: We see some of it happening just in vaccinated individuals.
DOUCLEFF: His lab research shows that months after the vaccine - just the vaccine - a person's antibodies begin to become more powerful, more flexible.
WHERRY: So the same antibody can actually detect and presumably neutralize the alpha variant, the beta variant and very likely the delta variant as well.
DOUCLEFF: But not all variants and not at the superb level they're seeing in people with prior natural infections. So the hope is that a third dose of the vaccine will boost these diversified antibodies and give even people who were never naturally exposed some of this exceptional protection against variants. And the superhuman immunity may then become super common.
Michaeleen Doucleff, NPR News.
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