By Sarah Jane Tribble, KHN

When the Food and Drug Administration announced last week that a third dose of Moderna or Pfizer-BioNTech covid-19 vaccine may boost the immunity of some people who are immunocompromised, officials repeated their stance that fully vaccinated, healthy people do not need another dose.

With this caveat: “The FDA is actively engaged in a science-based, rigorous process with our federal partners to consider whether an additional dose may be needed in the future,” said acting FDA Commissioner Dr. Janet Woodcock.

But the Biden administration reportedly said this week that most Americans will need a booster. And a White House press conference slated for 11 a.m. Wednesday was expected to address boosters.

Meanwhile, doctors and researchers caution that the public needs to stick to the advice of the FDA and the Centers for Disease Control and Prevention.

Those federal agencies “are doing their very best to ensure maximum protection and safety,” said Dr. Cody Meissner, a specialist in pediatric infectious diseases who sits on the FDA’s vaccine advisory panel. “People have to be very careful about statements that come from Big Pharma. They have a very different goal.”

Dr. Sadiya Khan, an epidemiologist and cardiologist at Northwestern University’s Feinberg School of Medicine, said that taking any medication has risks and that adding an additional dose of vaccine might cause unnecessary side effects. “What we need is data,” she said.

So what do we know about whether healthy, fully vaccinated people should get a booster? Here are answers to seven key questions.

1. What evidence are vaccine makers giving federal regulators to support the idea that an additional shot is needed?

It’s unclear how the booster may be authorized by regulators. On Tuesday, FDA spokesperson Abby Capobianco said federal agencies are reviewing laboratory and clinical trial data as well as data from the real world. Some data will come from specific pharmaceutical companies, but the agency’s analysis “does not rely on those data exclusively,” she said.

The companies, for their part, are racing to produce data. On Monday, Pfizer and BioNTech submitted initial but promising results from a phase 1 study of the safety and immune response from a booster dose given at least six months after the second dose. Late-stage trial results that evaluate the effectiveness of a third dose are “expected shortly,” Pfizer spokesperson Jerica Pitts confirmed this week.

Moderna President Stephen Hoge said during his company’s earnings call this month that a third dose is “likely to be necessary” this fall because of the highly contagious delta variant. Moderna spokesperson Ray Jordan said Tuesday the company is in talks with regulators but hasn’t provided an estimated timeline.

Johnson & Johnson, whose vaccine is administered in a single shot, hopes to share results soon from a late-stage clinical trial studying the safety and efficacy of a two-dose regimen in 30,000 adults. The study is looking at “potential incremental benefits” with a second dose, company spokesperson Richard Ferreira wrote in a Tuesday email.

2. Why might healthy people not need a booster yet?

Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and an adviser to the National Institutes of Health and FDA, said current federal guidance does not recommend a booster and there’s no “science-based” reason to get an additional shot at this time — even after receiving the J&J vaccine.

The current mRNA vaccines work by inducing a certain level of neutralizing, virus-specific antibodies with the first dose. Then the second dose brings on an exponential increase in the measurable level of specific neutralizing antibodies — and, more important, there’s evidence that the second dose of mRNA vaccine also gives cellular immunity, Offit said.

“That predicts relatively longer-term protection against severe critical disease,” he said. A single dose of the J&J vaccine — which uses a different technology, called an adenovirus vector — has been shown to provide the equivalent response to the second dose of an mRNA vaccine, he said.

3. How do the three vaccines authorized in the U.S. compare?

A recent preprint — a paper that has not been peer-reviewed — from the Mayo Clinic suggests that the Moderna vaccine may be more protective against the delta variant than the Pfizer-BioNTech vaccine. However, that research is based on examining the vaccination history of thousands of people who got covid, rather than a direct comparison of the vaccines, said Dr. Catherine Blish, a specialist in infectious diseases at Stanford Medicine.

“I would be hesitant to alter any practices or change behavior in any way based on that data,” she said.

The Moderna and Pfizer-BioNTech vaccines are administered differently, which could factor into how much mRNA the body receives to code into protein, said Dr. Monica Gandhi, a specialist in infectious diseases at the University of California-San Francisco. Moderna’s dosing is two shots of 100 micrograms delivered four weeks apart, while the Pfizer-BioNTech vaccine’s two 30-microgram doses are delivered three weeks apart.

At the end of July, Pfizer and BioNTech announced findings that four to six months after a second dose their vaccine’s efficacy dropped from a peak of 96% to about 84%. With its own data of fading efficacy, the Israeli government launched a vaccination campaign this month encouraging more than 1 million residents over age 50 to get a third shot.

As for J&J’s one-shot vaccine, there’s no evidence that recipients are being hospitalized with breakthrough infections at a higher rate than if they had received other vaccines, said Dr. Amesh Adalja, a specialist in infectious diseases at Johns Hopkins Center for Health Security.

4. Could a booster harm a healthy, fully vaccinated person?

It’s unclear. Offit said he believes a booster is safe and may well become important — but “it’s just not where we should be in this country right now.” The best defense against delta and other variants, he said, is to first vaccinate as many people as possible.

Others, though, said the available research signaled that caution is warranted. During a media briefing reported by Reuters last month, Jay Butler, the CDC’s deputy director for infectious diseases, said the agency was “keenly interested in knowing whether or not a third dose may be associated with any higher risk of adverse reactions, particularly some of those more severe — although very rare — side effects.”

The CDC did not respond to questions this week about its stance on potential risks. There have been reports of blood clots and allergic reactions after regular dosing. Khan, at Northwestern, said she is also concerned about reports of myocarditis, inflammation of the heart — which is more common after the second shot than the first. She said it’s not clear that the benefit of taking a booster would outweigh the risk for young, healthy people.

5. Would a booster limit a vaccinated person’s ability to spread the virus?

Dr. William Moss, a professor of epidemiology at Johns Hopkins’ Bloomberg School of Public Health, explained that the immune protection conferred by vaccines operates along a spectrum, from severely limiting initial virus replication to preventing widespread virus dissemination and replication within our bodies.

“Booster doses, by increasing antibody levels and enhancing other components of our immune responses, make it more likely virus replication will be rapidly prevented,” Moss said. “This then makes it less likely a vaccinated individual will be able to transmit the virus.”

Moss also said there are potential benefits to combinations of vaccines like those being administered in San Francisco and some European countries. German Chancellor Angela Merkel boosted her adenovirus-vectored AstraZeneca shot with Moderna in June.

Another possible step for pharmaceutical companies is to reformulate their covid vaccines to more closely match newer variants. Pfizer has announced it could do so within 100 days of the discovery of a variant.

Hopefully, the regulatory process could be expedited for such reformulated vaccines, said Moss, who works within Johns Hopkins’ International Vaccine Access Center.

6. Would we have to pay for the booster dose, or would it be free, like the previous shots?

It is expected to be free. According to Pfizer and the White House, the federal government purchased an additional 200 million doses of the Pfizer-BioNTech vaccine for inoculating children under 12 and for possible boosters.

7. Is there a future in which we take an annual covid shot?

Dr. Vincent Rajkumar, a hematologist at the Mayo Clinic who studies cancers involving the immune system, said a year ago he believed immune responses to covid may be similar to those of the measles, which create “a very long memory that protects us.”

Then covid mutated. “India changed everything for me,” he said, referring to its massive second wave after delta was discovered. Many of those who were infected had already had covid, he said.

Rajkumar now believes “we might need annual boosters — and it would be nice if such boosters can be combined with the flu vaccine.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

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