How does protection after infection compare to vaccination?
Two weeks after your final vaccine dose, protection against a COVID-19 infection is high -- around 90% for the Pfizer and Moderna mRNA vaccines and 66% for the one-dose Johnson & Johnson shot. Clinical trials conducted by the manufacturer have shown that a second dose of the Johnson & Johnson vaccine given at least 2 months after vaccination boosts protection against illness in the United States to about 94%, which is why another dose has been recommended for all Johnson & Johnson vaccine recipients 2 months after their first shot.
It’s not yet known how long the COVID-19 vaccines remain protective. There’s some evidence that protection against symptomatic infections wanes a bit over time as antibody levels drop. But protection against severe illness, including hospitalization and death, has remained high so far, even without a booster.
Are antibodies different after infection compared to vaccination?
Yes. And researchers don’t yet understand what these differences mean.
It seems to come down to a question of quality versus quantity. Vaccines seem to produce higher peak antibody levels than natural infections do. But these antibodies are highly specialized, able to recognize only the parts of the virus they were designed to target.
“The mRNA vaccine directs all the immune responses to the single spike protein,” says Alice Cho, PhD, who is studying the differences in vaccine and infection-created immunity at the Rockefeller University in New York. “There’s a lot more to respond to with a virus than there is in a vaccine.”
During an infection, the immune system learns to recognize and grab onto many parts of the virus, not just its spike.
The job of remembering the various pieces and parts of a foreign invader, so that it can be quickly recognized and disarmed should it ever return, falls to memory B cells.
Memory B cells, in turn, make plasma cells that then crank out antibodies that are custom tailored to attach to their targets.
Antibody levels gradually fall over a few months’ time as the plasma cells that make them die off. But memory B cells live for extended periods. One study that was attempting to measure the lifespan of individual memory B cells in mice found that these cells probably live as long as the mouse itself. Memory B cells induced by smallpox vaccination may live at least 60 years -- virtually an entire lifetime.
Dr. Cho’s research team has found that when memory B cells are trained by the vaccine, they become one-hit wonders, cranking out copious amounts of the same kinds of antibodies over and over again.
Memory B cells trained by viral infection, however, are more versatile. They continue to evolve over several months and produce higher quality antibodies that appear to become more potent over time and can even develop activity against future variants.
Still, the researchers stress that it’s not smart to wait to get a COVID-19 infection in hopes of getting these more versatile antibodies.
“While a natural infection may induce maturation of antibodies with broader activity than a vaccine does -- a natural infection can also kill you,” says Michel Nussenzweig, MD, PhD, head of Rockefeller’s Laboratory of Molecular Immunology.
Sure, memory B cells generated by infections may be immunological Swiss Army Knives, but maybe, argues Donna Farber, PhD, an immunologist at Columbia University in New York, we really only need a single blade.
“The thing with the vaccine is that it’s really focused,” she says. “It’s not giving you all these other viral proteins. It’s only giving you the spike.”
“It may be even better than the level of neutralizing spike antibodies you’re going to get from the infection,” she says. “With a viral infection, the immune response really has a lot to do. It’s really being distracted by all these other proteins.”
“Whereas with the vaccine, it’s just saying to the immune response, ‘This is the immunity we need,’” Dr. Farber says. “‘Just generate this immunity.’ So it’s focusing the immune response in a way that’s going to guarantee that you’re going to get that protective response.”