New Clues Show How the Immune System Fights COVID-19

When the immune system detects an invading virus like COVID-19, it sends swarms of antibodies to latch on to it, blocking its ability to attach to cells and marking it for destruction by other cells. Now, new research shows in striking detail how that process works in people who have successfully recovered from COVID-19 and offers new insights to help others.

So far, scientists have focused on one part of the coronavirus spike — the receptor-binding domain — which the virus uses to attach and gain access to human cells. This part of the coronavirus attaches directly to a person’s cells to infect them, and is the part that researchers have made their top priority for vaccine and drug development. The monoclonal antibody therapies approved last year for emergency use by the US Food and Drug Administration use this same target.

Now, a team led by immunologists Gregory Ippolito and Jason Lavinder, from the University of Texas at Austin, has taken a closer look at blood samples from four people who recovered from COVID-19 and found that most of the antibodies their bodies made to fight off illness actually targeted other parts of the coronavirus spike.

In fact, as much as 80% of their antibodies targeted other parts of the spike protein. These antibodies were aiming at another area of the umbrella-shaped protein’s canopy, Ippolito explains. And it is this part of the spike protein — called the N-terminal domain — that mutates most frequently. Changes in this region are responsible for many of the variants of concern. Such variants might be able to avoid detection by some of the most common antibodies in our defensive arsenal, evading the immune system.

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But another large group of antibodies targets the stalk of the spike, called the S2 subunit. That’s reassuring, the scientists report, because this is a region that does not mutate often, so if the antibodies that recognize the virus are able to neutralize it, they should offer a layer of protection against any variant.

No S2-binding antibodies have been found to be strongly protective yet, but Lavinder says that if some can be found, they could play a role in the next generation of vaccines and booster shots developed to deal with the variants. It could even point the way toward a vaccine that provides protection against all coronaviruses, not just COVID-19.

“The idea is that because this region is significantly conserved across all coronaviruses, it could make a good pan-coronavirus vaccine,” says Ippolito. “It could be important for the strategic design of vaccines in the future.”

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