On Wednesday, Oct. 20, the Food and Drug Administration (FDA) endorsed boosters for the Moderna and Johnson & Johnson COVID vaccines, following recommendations from an FDA advisory committee. A day later, the Centers for Disease Control and Prevention (CDC) did the same, significantly expanding eligibility for millions of Americans to get these follow-up shots.

“The evidence shows that all three COVID-19 vaccines authorized in the United States are safe, as demonstrated by the over 400 million vaccine doses already given,” CDC Director Rochelle Walensky said in a statement. “They are all highly effective in reducing the risk of severe disease, hospitalization, and death, even in the midst of the widely circulating Delta variant.”

This news comes just a month after a late-September change endorsed administration of a booster for many people who had previously received the FDA-approved Pfizer/BioNTech vaccine. Penn Medicine pediatric oncologist and bioethicist Steven Joffe and immunologist E. John Wherry discuss what’s currently known about these boosters, including what happens in the body when people get one and whether it’s safe to get a flu shot at the same time.

1. The authorizations don’t apply to everyone

On Sept. 22, the FDA made certain groups eligible for a Pfizer booster. “Specifically, if you’re 65 or older and you got Pfizer upfront, you could go get a third dose six months from your last shot,” Joffe says.

“If you’re 18 to 64 and you have a chronic medical condition or you have frequent occupational or institutional exposure—for instance, health care workers, grocery store workers, teachers, jail and prison workers and inmates, or residents of long-term care facilities—you can get a booster too, again at the six-month mark,” he adds. The CDC agreed with the FDA, issuing similar guidance two days later.

Because the Moderna and J&J vaccines are not yet FDA-approved, the companies applied to amend to their respective Emergency Use Authorizations to include a booster. Moderna did not seek blanket authorization like Pfizer and J&J had done, but rather for anyone older than 65, plus 18- to 64-year-olds with risk factors for severe COVID or jobs that made them more susceptible. The FDA and CDC gave the greenlight for these specific groups, the same ones approved for the Pfizer booster.

“At the moment, getting the Pfizer and Moderna boosters approved for all adults is not on the agenda,” says Joffe. “The Biden Administration wanted it on the agenda, but there’s been enough skepticism in the medical and scientific communities that for now, at least until more data come in, the focus will remain on specific high-risk groups.”

No restrictions were placed on the J&J vaccine booster, meaning anyone 18 or older who got this single shot the first time around can now get a second one, as soon as two months after initial vaccination. The FDA and CDC also authorized a “mix and match” approach, meaning Americans can get a different COVID booster than the vaccine they originally received.

2. Booster formulations match the initial vaccine, though dosing may vary 

“For Pfizer, it’s the same dose, the same formulation, the same parts of SARS-CoV-2 being expressed,” Wherry says. The same is true for the J&J booster. But Moderna’s booster is half the dose of the original shots, 50 micrograms compared to 100 micrograms.

3. The boosters top off antibody levels

When COVID vaccines enter the body, the body mounts an immune response. “A couple parts of the immune system get activated. You generate a little inflammation, which tells the immune system to get the troops ready,” says Wherry. “That allows the immune system to activate T and B cells.”

T cells fight off disease themselves, and some coach B cells to make as many antibodies as possible through induction of plasma cells and then memory B cells, which can last in the body for years. “These antibodies act like sticking a piece of gum in a lock so the key can’t get in,” Wherry says. “That’s what happens when the antibodies coat the virus. It’s like putting gum on the key. It prevents the virus from being able to unlock the door to get into your cell.”

As antibody levels decrease—the amount of gum, in Wherry’s analogy—protection against the virus likely drops. That’s where the boosters come in, reminding the memory B cells still in the body to make antibodies again. “This can all happen way faster than it happened the first time, within a few days,” he says.

4. It’s safe to get a COVID shot and flu vaccine at the same time

Recently, the CDC offered guidance on the upcoming influenza season, some of which addressed the question of whether people can receive both a flu vaccine and their COVID vaccines or boosters simultaneously. The answer is yes, though the agency reminded people to follow the recommended schedule for whichever COVID vaccine they get.

To Wherry, there’s a public health consideration, too. “If you have one chance to get people in the clinic and get them vaccinated with both shots, I definitely subscribe to that,” he says. “If you have a highly engaged patient population, on the other hand, maybe you want to space these out a little, mostly because we do know that the mRNA vaccines can induce a good amount of inflammation.”

Steven Joffe is the Art and Ilene Penn Professor of Medical Ethics & Health Policy and a professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania. He is also director of the Penn Fellowship in Advanced Biomedical Ethics and the Penn Postdoctoral Training Program in the Ethical, Legal, and Social Implications of Genetics and Genomics.

E. John Wherry is the chair of the Department of Systems Pharmacology and Translational Therapeutics and the Richard and Barbara Schiffrin President’s Distinguished Professor at the Perelman School of Medicine. He is also the director of the Institute for Immunology at Penn.