Killer T cells, as their name might imply, are not known for their mercy. When these immunological assassins happen upon a cell that’s been hijacked by a virus, their first instinct is to butcher. The killer T punches holes in the compromised cell and pumps in toxins to destroy it from the inside out. The cell shrinks and collapses; its perforated surface erupts in bubbles and boils, which slough away until little is left but fragmentary mush. The cell dies spectacularly, horrifically—but so, too, do the virus particles inside, and the killer T moves on, eager to murder again.
It’s all a bit ruthless, but the killer T does not care. It is merely adhering to its creed: Virus-infected cells must die so that the rest have a better shot at living. The cold-blooded slaughter can “make the difference between someone having a mild infection and a severe one,” Azza Gadir, an immunologist and scientific advisor at the microbial sciences company Seed Health, told me. And that’s exactly what experts now hope is happening in vaccinated people whose antibodies might be faltering against Omicron, the new coronavirus variant that’s sweeping across the globe. T cells can’t totally forestall infection on their own, so we still need the other strategies we use to keep the virus at bay. But prepped by shots or past infection, these elite killers could help hold the line against hospitalizations and deaths, and offer a safety net that could spare us some of the coronavirus’s worst effects.
Enough preliminary data have been gathered to show that Omicron can undermine some of the defenses that immunized bodies have built. The variant’s spike protein—the molecular key that the virus uses to unlock cells, and the centerpiece of most of the world’s COVID-19 shots—sports more than 30 mutations compared with the original SARS-CoV-2. Last week, several teams of scientists, as well as Pfizer, released early laboratory data suggesting that these tweaks might make the variant up to 41 times better at sidestepping the neutralizing antibodies roused by vaccines. In an actual body, that could make it easier for Omicron to kick-start an infection.
But infection doesn’t always guarantee serious disease. And neutralizing antibodies are not the only defense that the immune system can muster. Immune responses are layered and redundant; where one squadron falters, another can swoop in to help. Killer Ts represent one such layer, and their violent modus operandi comes with serious perks: They home in on different aspects of the virus than antibodies do, and they are much harder to stump with mutations. Against Omicron, T-cell protection might drop slightly, Tao Dong, an immunologist at Oxford University, told me. “But it is not something we should be really worried about.”
Antibodies are powerful but simple sentinels. Squeezed out by B cells, they spend their days wandering the body, trying to glom on to a super-specific anatomical sliver on a pathogen. When they manage the feat, some of them—the neutralizers—can cling on so tightly that a virus becomes unable to interact with and enter cells. “That’s why we care so much about antibodies,” Andrew Redd, an immunologist at the National Institute of Allergy and Infectious Diseases, told me. They can block infection solo; the rest of the immune system never has to get involved.
That perfect scenario doesn’t always play out, though. After vaccination or infection, antibody levels skyrocket—then, slowly but surely, they start to tick down, giving pathogens more opportunities to sneak by. Neutralizing antibodies are also easily duped by mutations that even slightly rejigger a microbe’s superficial features. Where they once clung on tight, they’ll simply slip off. Viruses, then, have both time and mutations on their side: Infections become easier as antibodies disappear and microbes metamorphose. And once a pathogen has foisted its way inside a cell, it becomes “inaccessible to [neutralizing] antibodies,” Alessandro Sette, of the La Jolla Institute for Immunology, told me. The relevant bits of the bug are no longer visible to them, so they just whiz on by.
But where antibodies stumble, killer Ts shine. Their entire raison d’être is rooting out infected cells—not free-floating viruses—and they manage that feat through an affinity for gore. As a signal of distress, infected cells can chop up some of the viruses they’re being forced to produce and display the mangled pieces on their outside. “They say, ‘Look, I’m infected with something,’” Avery August, an immunologist at Cornell University, told me. The dismembered bits are gross but effective: Nothing makes killer Ts go wild more than a hunk of mutilated virus splattered onto the surface of an infected cell.
While neutralizing antibodies pinpoint viruses by their external traits, the microbe equivalent of hair and skin, killer Ts can also identify them via their innards—the blood, muscle, and bone underneath. And because the virus is pretty mashed up at this point, T cells aren’t always as flummoxed by mutations as are antibodies, which care intimately about shape. “That all makes it much more difficult for the virus to evade T-cell responses,” Gadir, of Seed Health, said. SARS-CoV-2 would have to alter a lot more of its physiology to successfully disguise itself—revamping its outsides with plastic surgery, and reshuffling its internal organs with transplants—something the virus might not be able to accomplish without compromising its ability to hack into our cells.
Even if the coronavirus somehow managed a major makeover, it would still have to outsmart another trick: Thanks to a genetic quirk, different people’s infected cells will parade different bits of the virus in front of killer Ts—a hand and a liver in you, an ear and a kidney in me. Which means that a version of the virus that manages to elude T cells in one person might still be completely trounced in the next. “That really protects us on a population level,” August said. T cells, in this way, can hamper the spread of infection both within bodies and among them.
All of this coalesces into a not-totally-catastrophic forecast as to where the immunized could be headed with Omicron. Some T cells might waver—but a hefty contingent should still rush in to fight when the variant invades, as long as a vaccine or prior infection has already wised them up. We don’t, to be fair, have the full picture on Omicron yet; more data are still on their way. What’s known so far, though, looks promising. New data gathered by teams led by Sette and Redd show that most of the viral bits that trained T cells tend to recognize, including those within the spike protein, are still pristinely preserved on Omicron, with only a few exceptions. In previously infected people, for instance, Sette’s team predicted that some 95 percent of spike-specific killer Ts should still hit their mark; in the vaccinated, it was 86 percent. Similar data from Pfizer, as well as the biotech company Adaptive, clock in closer to 80 percent for the inoculated. (T cells sampled from vaccinated individuals fixate on the spike—the only thing shots showed them—but T cells in previously infected individuals would be able to home in on other parts of the coronavirus’s anatomy as well.)
So there’s probably a dip in how well T cells can suss out Omicron, but not a massive one. And it’s in line with what researchers have observed with other SARS-CoV-2 variants with a wonky-looking spike: T cells consistently pummeled them, because they hadn’t switched up most of the snippets that made them vulnerable to detection, and our vaccines still worked. Omicron, admittedly, is more deviant, and scientists still need to test how well T cells perform against chunks of the variant—something Sette’s group is working on now. But Sette stressed that the important takeaway is that a lot of the T-cell response should still be effective—which means that “the capacity of the immune system to limit the spread of the virus … would still be preserved.”
T cells “become even more important if antibodies are not working well,” Dong said. Cellular infections might start to roll out at a rapid clip, but T cells can swoop in to help corral the pathogen in place, typically within a couple of days. This rapid walling-off can halt the progression of disease, and maybe even curb transmission; it also buys the rest of the immune system time to gather its wits. B cells, reawakened from their slumber, will start to churn out more antibodies to replace the ones that have faded; another group of T cells, nicknamed the helpers, will arrive to help coordinate the rest of the immune response. Getting a booster, too, could jump-start this process ahead of infection, coaxing out extra antibodies and possibly tickling more T cells into joining the fray.
All of this is likely to mean that more vaccinated people could get infected by Omicron—a new and unfortunate hurdle, as the world continues its struggle to contain the super-transmissible Delta. But the immunized will probably still be at much lower risk of getting seriously sick than their unvaccinated peers, a pattern that early studies out of South Africa seem to fit. That’s in keeping with the stepwise fashion in which immune protection tends to ebb: The safeguards against infection—mostly neutralizing antibodies—fall first. But protection against severe disease and death is the last to go; to engineer those very serious outcomes, viruses have to linger in the body, repeatedly thwarting the many defenders that the immune system tosses their way.
But our shot-trained T cells can’t be expected to stand their ground forever. Too many people around the world remain unvaccinated, offering the virus many more chances to splinter into new, troublesome lineages. The quicker the virus moves to colonize us, the more likely it is to outpace our defenses. SARS-CoV-2 could eventually learn to hopscotch over more killer Ts, too—a risk we run when we force our bodies to repeatedly tussle with this fast-changing foe.