An integral but overlooked part of our immune systems may help keep most vaccinated people out of the hospital if they catch Omicron. A flurry of new studies suggests that T cells can extinguish Omicron infections and prevent mild diseases from becoming severe, even as the virus evolves to evade our antibodies.
“If you weren’t boosted, your antibodies have waned over time, and it is likely that T cells are the reason that you are still not getting very sick,” said Dr. Steven Varga, a professor of microbiology and immunology at the University of Iowa who wasn’t involved in the new studies.
Most immunologists and vaccine developers have focused on studying antibodies during the pandemic, and for good reason. High levels of neutralizing antibodies can stop the virus in its tracks by physically blocking its ability to infect cells. But when some viruses slip past the antibodies — as Omicron often does — the immune system’s T cells swoop in as backup.
COVID-19 vaccines train T cells to seek and destroy virus-infected cells, helping to quell infections before they worsen. This second line of defense is looking increasingly important; while many antibodies may not be as strong against subsequent mutations of the virus, most T cells should be able to hold their own.
Several studies recently published by researchers in Africa, Europe, and the United States show that most vaccinated people have T cells that can vanquish Omicron infections, even when they don’t have a robust antibody response to the variant.
“It was an absolute relief,” said Dr. Wendy Burgers, an immunologist at the University of Cape Town in South Africa, who co-led one of the studies. Her team found that about 70 to 80 percent of T cells that recognized the original SARS-CoV-2 could still target Omicron in vaccinated or previously infected people.
At least five other groups of researchers have now shown that about 80 percent or more of vaccinated people’s T cells that were trained to target the coronavirus can still recognize Omicron. “It is a really compelling consensus,” said Dr. Alessandro Sette, who co-led one of the studies at the La Jolla Institute for Immunology.
Although T cells are no secret to scientists, compared with antibodies they are often an afterthought. “T cells have largely been ignored,” said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, who led one of the studies. “Now we are seeing how important T cells are for protection against new variants that might emerge.”
The lab studies were done on T cells previously taken from the blood of vaccinated or infected people and pitted against little fragments of the Omicron variant designed to mimic what the T cells would encounter during an infection.
But some scientists are seeing the new T cell data in a different light. Most of the studies found that a minority of people, between 15 and 20 percent, did not have T cells that could hunt down Omicron infections — the largest loss of T cell immunity for any variant yet.
“This is probably the first variant we’ve seen that evolves away from the T cell response for some reasonable subset of people,” said Dr. Gaurav Gaiha, a gastroenterologist at Massachusetts General Hospital and a researcher at the immunology-focused Ragon Institute of Mass. General, MIT and Harvard University.
Gaiha and Dr. Vivek Naranbhai, an oncologist at Mass. General and the Dana-Farber Cancer Center, have conducted their own study of antibody and T cell responses in vaccinated or previously infected people. Like others, they found that T cell immunity is sustained against Omicron in most people, but their study emphasized that T cell responses significantly declined in about 20 percent of people.
“For some people, you may start seeing variants that are able to escape both antibody and T cell response,” Naranbhai said. “We don’t know what the next variant will look like, but the concern is that it will be a variant that can escape both.”
Although scientists can’t say for certain how many T cells a person needs to be protected from severe disease, Gaiha and Naranbhai found that booster shots improved both antibody and T cell immunity. Many scientists believe that even the elevated antibody levels from a booster will inevitably drop off, and that T cells could provide a more durable response to the ever-changing virus.
“It is much more difficult for a virus to avoid T cell responses,” said Dr. Rory D. de Vries, a virologist at Erasmus University Medical Center in the Netherlands.
Most antibodies that vaccinated people produce stick to two small regions of the coronavirus spike protein that are crucial for the virus’s ability to cause infection. Omicron has more than two dozen mutations in those regions, making it difficult for most antibodies to recognize the virus.
T cells are less picky and can target a broader swath of the spike protein, including regions that don’t mutate as often, making it harder for the virus to outwit T cells. Scientists have seen this repeatedly during the pandemic.
“Every variant that has come up so far has been recognized by T cells, even when there is evasion of the antibody response,” said Dr. Joel Nee-Lartey Blankson, an infectious disease doctor at Johns Hopkins Medicine. “So it shows us that T cells will probably protect us from variants to come down the pike.”
A recent study from de Vries’s lab stands out for suggesting that T cell immunity is unchanged against Omicron. He says that if the reduction in T cell immunity that other groups are seeing is true, “it is something to keep an eye on.”
But he added that T cells may not be absent after all, just hiding. They can park themselves in other parts of the body, not just the bloodstream, waiting to spring into action as needed.
Right now, all commercial COVID-19 vaccines are based on the coronavirus spike protein, which antibodies must target to prevent infection. Some small biotech companies and academic scientists are designing vaccines that incorporate other parts of the coronavirus that mutate less frequently than the spike. Training T cells on those parts of the virus could help them spot future infections early and keep illnesses from becoming severe, even as the virus continues to evolve.
This emphasis on preventing severe disease, rather than infection, could become more important moving forward. Last week, a CDC report showed that a booster shot of an mRNA vaccine was 91 percent effective at preventing hospitalizations two months after vaccination, but the effectiveness dropped to 78 percent at four months.
“So there is still relatively good protection against hospitalization, and T cell responses likely contribute,” Barouch said.
To be clear, immunologists say that having antibodies and T cells working together is optimal, but some think it is time to be relying on our T cells more.
“I would argue that it is time to recalibrate the expectations of vaccines. The expectation should really be prevention of severe disease. The focus should never have been prevention of all infection, because that is unattainable,” Barouch said. “The importance of T cells has become clearer with the Omicron surge.”