The Perfect Enemy | No One Knows if You Need Another Covid Booster - WIRED
May 14, 2024

The US Food and Drug Administration is pushing for you to get an annual Covid booster. The problem is, the data isn’t clear on whether you need one. 

Covid isn’t going anywhere. In the US and many European countries, SARS-CoV-2 is still circulating at significant levels, with Covid settling into being a major, ongoing cause of illness. Boosters may protect against its worst effects, but these are shots in the dark: insurance against severe disease, but possibly not necessary. This is because we don’t know how long their protection against severe illness actually lasts. 

It’s time we found out, but that means switching focus. At the level of basic biology, it means paying less attention to the antibodies vaccines generate and focusing more on another very important but overlooked part of the immune system: memory T cells. “The way you’re going to know who needs boosters is to know how long memory cells last,” says Paul Offit, a professor of vaccinology at the University of Pennsylvania and a vaccine advisor to the FDA.

The immune system is complex, but fundamentally it has three parts. There’s innate immunity, the physical or chemical barriers—such as your skin or the mucus in your nose—that are constantly working to keep disease-causing microbes at bay. 

For germs that get past this, there’s then short-term or humoral immunity: the rapid response tailored to a particular invading threat, such as a virus, that dominates early after it has arrived to try to keep an infection from taking hold. This defensive wave is led by neutralizing antibodies made specifically to fight whatever has invaded the body. 

But when this antibody response fails to stop Covid from gaining a foothold and the virus gets inside cells so it can reproduce, a third protective strand comes into play: long-term, cellular immunity. Memory T cells, which are also tailored to the specific threat, are a key part of this. 

“Once a virus infects cells, T cells can then limit the amount of viral replication,” says Céline Gounder, an infectious disease specialist and editor at large at KFF Health News. When a virus like Covid reproduces, it parks parts of itself in the outer membrane of the cell, which announces to the host that the cell is infected. T cells—primed, through vaccination or prior infection, to notice these odd parts—then kick into gear, killing infected cells and directing the production of more antibodies. “That’s preventing the disease from progressing,” Gounder says. 

So while cellular immunity doesn’t stop an initial infection, it’s what keeps people out of the hospital, out of the intensive care unit, and out of the morgue, says Offit. “The second thing that’s good is that T cells often live for years, decades, or lifetimes,” he says—meaning the protection they offer against severe illness can be long-lasting. 

And there’s a third major benefit. In Covid, some of the viral bits that wind up on cell membranes and attract T cells are “highly conserved” interior parts of the coronavirus—bits that are much less likely to mutate and become invisible to the immune system. The proteins that coat the outside of the virus, which are what typically end up being targeted by antibodies, are much more likely to mutate, leaving those antibodies less effective.