Ahead of a two-day meeting that could clear the way for offering booster shots to millions more Americans, scientists from the Food and Drug Administration made a careful presentation of available data from Moderna and Johnson & Johnson, but stopped short of advocating strongly for authorizing an additional dose of either company's vaccine.
In separate briefing documents, which are meant to lay out the FDA's position before outside advisers meet Thursday and Friday, agency staff appeared to take a cautious view on whether booster doses are needed now.
Overall, "data indicate that currently US-licensed or authorized COVID-19 vaccines still afford protection against severe COVID-19 disease and death in the United States," FDA scientists wrote in their review of Moderna's application for clearance of a third dose.
They said much the same in their review of J&J's application, although they noted the efficacy of the company's one-shot vaccine was less than the two-shot messenger RNA regimens from Moderna and Pfizer.
Agency staff were similarly neutral in their review of Pfizer's application last month, however, and the FDA eventually authorized booster doses of that vaccine for many of the most vulnerable Americans.
Moderna had originally asked the FDA to clear a booster dose of its vaccine for individuals 12 years and older. But the company amended its request to match what the FDA authorized for Pfizer's shot on Sept. 22. That clearance, granted after back-and-forth meetings of advisers to both the FDA and the Centers for Disease Control and Prevention, included adults over 65, younger adults with underlying medical conditions and individuals older than 18 whose "frequent institutional or occupational exposure" puts them at higher risk.
Importantly, Moderna is proposing using a third dose that's half the size of the first two. J&J, by comparison, is asking for the FDA to clear a second dose that's the same as the first.
Advisers are likely to spend time Thursday and Friday debating booster safety. During their meeting on authorization of Pfizer's booster, committee members were focused on the risk of myocarditis, an inflammation of the heart that's been associated in rare cases with mRNA vaccination, particularly in younger men. (COVID-19 can also lead to myocarditis.)
That discussion will likely repeat, as a similar pattern has been observed with Moderna's vaccine as with Pfizer's.
"Information is not yet available about potential long-term sequelae and outcomes in affected individuals, or whether the vaccine might be associated with initially subclinical myocarditis," the agency noted in the briefing.
Much of Moderna's case for a booster shot, which would be given six months after the second dose, relies in large part on data showing antibody levels decline over time, as well as the higher threat from the delta variant.
J&J also draws on antibody data, as well as results from a late-stage clinical trial that tested two doses of its vaccine spaced two months apart. Two immunogenicity studies, meanwhile, looked at spacing doses two to three months after the first or six months after. Results from both showed an rise in antibody levels, although the increase was greater with the six-month interval.
Some of that data appears to have factored into J&J's request for more flexible timing of a potential booster dose between two to six months after the first in people older than 18.
FDA staff indicated the agency intends to seek advice from its advisers on the ideal timing of a second J&J dose.
A larger question facing the regulator, however, is whether mixing booster shots could better protect people after their primary vaccination with another vaccine. That debate could be particularly relevant for J&J's vaccine, which the FDA noted has efficacy that's "consistently less than the highest effectiveness estimates for the mRNA COVID-19 vaccines."
The committee will hear from the National Institutes of Health on a study examining this so-called heterologous boosting strategy. That presentation, however, will occur on Friday, after the committee has been asked to vote on their recommendations for both vaccines.