Boosters coming, but who will get them and when?

COVID-19 booster shots are on the way for at least some Americans, but already the Biden administration is being forced to scale back expectations — illustrating just how much important science still has to be worked out.

The initial plan was to offer Pfizer or Moderna boosters starting Sept. 20, contingent on authorization from U.S. regulators. But now administration officials acknowledge Moderna boosters probably won’t be ready by then — the Food and Drug Administration needs more evidence to judge them. Adding to the complexity, Moderna wants its booster to be half the dose of the original shots.

As for Pfizer’s booster, who really needs another dose right away isn’t a simple decision either. What’s ultimately recommended for an 80-year-old vaccinated back in December may be different than for a 35year-old immunized in the spring — who likely would get a stronger immunity boost by waiting longer for another shot.

FDA’s scientific advisers will debate Pfizer’s evidence Sept. 17, just three days before the administration’s target. If the FDA approves another dose, advisers to the Centers for Disease Control and Prevention will recommend who should get one.

That’s tricky, because while real-world data shows the vaccines used in the U.S. remain strongly protective against severe disease and death, their ability to prevent milder infection is dropping. It’s not clear how much of that is due to immunity waning or the extracontagious delta variant — or the fact that delta struck just as much of the country dropped masks and other precautions.

When to jump to boosters “becomes a judgment,” said Dr. Jesse Goodman of Georgetown University, a former FDA vaccine chief. “And is that urgent or do we have time for the data to come in?”

Already the CDC is considering recommending the first boosters just for nursing home residents and older adults at highest risk of severe disease if their immunity wanes — and to front-line health workers who can’t come to work if they get even a mild infection.

Here’s what we know about the biology behind booster decisions:

What do boosters do?

Vaccines train the immune system to fight the coronavirus, including by producing antibodies that block the virus from getting inside cells. People harbor huge levels right after the shots. But just like with vaccines against other diseases, antibodies gradually drop until reaching a low maintenance level.

A booster dose revs those levels back up again.

Pfizer and Moderna have filed FDA applications for booster doses, but the government will decide on extra Johnson & Johnson doses later once that company shares its booster data with the agency.

How much protection will people get?

No one yet knows “the magic line” — the antibody level known as the correlate of protection below which people are at risk for even mild infection, said immunologist Ali Ellebedy of Washington University at St. Louis.

But vaccines’ main purpose is to prevent severe disease.

“It’s a very high bar to really go and say we can completely block infection,” Ellebedy noted.

Plus, people’s responses to their initial vaccination vary. Younger people, for example, tend to produce more antibodies to begin with than older adults. That means months later when antibody levels have naturally declined, some people may still have enough to fend off infection, while others don’t.

That initial variation is behind the FDA’s recent decision that people with severely weakened immune systems need a third dose of the Pfizer or Moderna vaccine to have a chance at protection.

Won’t antibodies just wane again?

Eventually. “We don’t know the duration of protection following the boosters,” said Dr. William Moss of Johns Hopkins University.

But antibodies are only one defense. If an infection sneaks past, white blood cells called T cells help prevent serious illness by killing virus-infected cells. Another type called memory B cells jump into action to make lots of new antibodies.

Those back-up systems help explain why protection against severe COVID-19 is holding strong so far for most people. One hint of trouble: CDC has preliminary data that effectiveness against hospitalization in people 75 and older dropped slightly in July — to 80 percent — compared with 94 percent or higher for other adults.

“It’s much easier to protect against severe disease because all you need is immunologic memory. And I would imagine for a younger person that would last for a while,” maybe years, said Dr. Paul Offit, a vaccine expert at the Children’s Hospital of Philadelphia.