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One of the key mysteries surrounding the novel coronavirus is whether people who recover from COVID-19 develop lasting immunity that will protect them from becoming reinfected in the future. It’s still going to be awhile before we can answer this question for certain. However, a report published May 14 in the journal Cell offers some encouraging signs about how our immune systems respond to SARS-CoV-2, the virus that causes COVID-19.

The researchers found that the immune system responds to the novel coronavirus in multiple ways. Importantly, they observed that people who recover from COVID-19 carry immune cells in their blood called T cells that target the novel coronavirus. T cells are a key component of the immune system’s ability to fend off infectious diseases. When faced with fragments of SARS-CoV-2, the T cells recognized the virus and sprang into action.

“Overall I think our findings are very good news and thankfully in keeping with what we would expect for a viral infection, especially in a normal population that seems to do well and doesn’t get severe disease,” says Sydney Ramirez, a virologist and infectious disease physician at the La Jolla Institute for Immunology and the University of California San Diego School of Medicine. “It’s speculation at this point, but it makes us think that we’re going to see protective immunity because [the immune response] looks similar to what we see with…better studied viruses that have been around longer.”

These results are “not unexpected but very reassuring,” says Paula Cannon, a professor of molecular microbiology and immunology at the Keck School of Medicine of the University of Southern California in Los Angeles who was not involved with the research.

“It’s an unremarkable virus—it seems to induce a very typical and classical immune response, and the type of immune response that develops in infected people gives us a blueprint for…a vaccine,” she says. “The results were what I think vaccine developers would have expected and hoped for.”

For the experiment, Ramirez and her colleagues collected blood samples donated by 20 adults who’d recovered from relatively mild cases of COVID-19 and exposed them to proteins from SARS-CoV-2. They saw that all 20 of the blood donors had produced antibodies—proteins that recognize and help fight pathogens the body has encountered before—to SARS-CoV-2. These included the kind of antibodies that are typically associated with long-term immunity to viruses, Ramirez says.

She and her team also detected two types of T cells that sprung into action when viral proteins were near. All the blood donors carried “helper” T cells, which rouse the immune system and assist antibody-producing immune cells. About 70 percent of the donors harbored “killer” T cells, which seek out and destroy cells that have been infected by the virus.

While the T cells reacted most strongly to the spike protein, they also recognized several other proteins from SARS-CoV-2. “The spike is really a fantastic protein because it’s able to trigger both antibody immune responses and T cell immune responses,” says Alba Grifoni, an immunologist at the La Jolla Institute and another coauthor of the new research. “But other proteins also seem to play a major role in the immune response.”

Ramirez agrees. “We’re reassured that we see such a robust response to the spike; there is hope that those vaccines will work,” she says. “[But] we can see that it doesn’t completely mimic natural infection to only focus on the spike protein.”

The majority of the vaccine candidates under development for COVID-19 are designed to elicit an immune response against the virus’s spike protein. Two such vaccines created by the Massachusetts-based biotech company Moderna and researchers at Oxford University are being tested in people. The new study indicates that vaccine developers are on the right track, Cannon says. “It tells us that…the emphasis on the spike protein was not misguided.”

However, the findings also raise the possibility that COVID-19 vaccines may be more effective if they include multiple components of the virus. One example of this kind of vaccine is being developed by the Beijing-based company Sinovac Biotech. The vaccine includes an inactivated, or “killed,” version of the virus and has successfully protected rhesus macaques from infection.

Ramirez and her colleagues also investigated how immune cells from stored blood samples that had been collected between 2015 and 2018—well before the novel coronavirus appeared on the scene—reacted to the viral proteins. Intriguingly, when confronted with the novel coronavirus, helper T cells from roughly half of the blood donors became activated. The researchers speculate that the people who donated these blood samples had previously been infected by other members of the coronavirus family that routinely cause common colds and developed an immune response that could also recognize SARS-CoV-2 as an enemy.

“The fact that someone who has never seen the virus is already able to recognize a piece of it, that’s extremely interesting and maybe that could lead to a more protective immune response,” Grifoni says. “That also suggests that perhaps donors who have a very strong response against the common cold [coronaviruses] might respond better or differently to the vaccine.”

There are cases where people who defeat certain viruses have an advantage against similar foes. During the 2009 swine flu pandemic, younger people were struck harder by the disease than older folks who might have encountered similar strains of influenza earlier in their lives.

However, she adds, there’s also a chance that prior exposure to similar coronaviruses would instead leave a person more vulnerable to future infection. People who encounter one type of dengue virus are more likely to become severely ill if they are later infected by a different dengue virus. While this kind of immune response is unusual, further studies will be needed to determine whether and how prior exposure to common cold coronavirus might affect a person’s immune response to SARS-CoV-2 or to a COVID-19 vaccine.

One limitation of the new study is that the researchers only examined blood samples from people with mild cases of COVD-19. The team is now collaborating with laboratories around the world to investigate how the immune response to SARS-CoV-2 differs among people with asymptomatic, mild, and severe illnesses and to track whether it changes over time.

While the new findings cannot confirm that people who catch COVID-19 go on to develop protective, long-term immunity, Cannon says, they do suggest that a vaccine for the novel coronavirus should be very attainable.

“I’m impressed with how quickly and thoroughly we can get a snapshot of what the immune system does in a normal COVID infection,” she says. “It was striking to me how consistent the observations were from all 20 [donors], which [gives] me confidence that this is a pretty standard virus in terms of how it’s seen and responded to by the immune system.”

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