OCTOBER 12, 2021
A Food and Drug Administration review released Tuesday found that a booster shot of the Moderna coronavirus vaccine enhanced virus-fighting antibodies in people who had received the standard two-dose regimen at least six months earlier.
The document, like a previous review of evidence for a booster of Pfizer-BioNTech, struck an ambivalent tone about whether boosters are needed now.
FDA reviewers noted that a half-dose booster shot of the Moderna vaccine topped off the level of antibodies, the most easily measurable barometer of immunity. But they also pointed out that the utility of a booster will depend on factors that are unclear at this moment — such as whether the protection of initial vaccination has dropped substantially.
“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,” the reviewers wrote.
The document was one of a series posted online in advance of a two-day meeting scheduled for Thursday and Friday at which independent experts will advise the agency on questions related to boosters, including: Are extra shots of coronavirus vaccines developed by Moderna and Johnson & Johnson safe and effective? Do data suggest people can safely take a booster dose made by a company different from their original shot?
On Thursday, advisers are expected to consider data supporting a third shot of Moderna, which would be the equivalent of a half-dose of the original shot. The booster would be administered at least six months after initial vaccination.
On Friday, they are scheduled to review evidence for a second shot of the Johnson & Johnson vaccine six months after vaccination.
The advisers are also slated to consider data from a National Institutes of Health trial that tested mixing and matching boosters, which could simplify boosting.
A third shot of Pfizer-BioNTech’s vaccine was authorized by the FDA for some people — including adults 65 and older and people at risk of severe illness or exposed to the virus at work. Moderna is seeking authorization of its booster for the same portion of the population “in the interest of public health,” the company said in a document it filed with the FDA. Johnson & Johnson said its data show a “favorable benefit-risk profile” for a booster dose in people 18 and older.
A key FDA official overseeing vaccines signaled last week that his hope was to come up with a “harmonized approach” for boosters for people who received any of the three vaccines available in the United States. Peter Marks, director of the Center for Biologics Evaluation and Research, said during a webinar that emerging data may support broad eligibility for boosters of all three shots — for anyone 18 and older.
The FDA document reviewing the Moderna data, like the one for Pfizer-BioNTech, notes that the authorized and approved vaccines overall provide protection against severe disease and death. It also states that key factors in the recent surge of the coronavirus in the United States include the emergence of the highly contagious delta variant, uneven use of public health measures to stop transmission and the millions of unvaccinated people. Notably, it does not cite waning immunity from vaccinated people as a key driver of the pandemic.
“Some real world effectiveness studies have suggested declining efficacy of Moderna COVID-19 Vaccine over time against symptomatic infection or against the Delta variant, while others have not,” the review said.
The Moderna findings under consideration include data on third shots given to nearly 350 people. Half of the people in the study received the standard two-dose regimen to start, followed with a booster. The other people got two doses to start but at half the size of the usual regimen before then receiving a booster. The trial measured virus-fighting antibody levels as a way of inferring that the booster would restore protection.
Moderna, in documents submitted to the FDA, cited a preprint study of vaccinated individuals from Kaiser Permanente Southern California that showed vaccine efficacy declined modestly against delta over time, from 94 percent immediately after vaccination to 80 percent efficacy five to six months after vaccination. Vaccine efficacy was also lower among people older than 65.
“We still see people are very protected against severe outcomes, but against infection overall there is a modest reduction in the [vaccine efficacy] and that suggests that boosters likely do play a role as part of the vaccine strategy,” said Katia Bruxvoort, an adjunct investigator at Kaiser Permanente Southern California who led the analysis.
One potential sticking point if there is an effort to harmonize access to vaccine boosters by broadening eligibility to people 18 and older: the small but real risk of myocarditis — heart inflammation — after vaccination, particularly among younger men. No cases of such inflammation were deemed linked to the vaccine in the small trial.
“It is currently not known if there will be an increased risk of myocarditis/pericarditis or other adverse reactions after a booster dose of the Moderna COVID-19 Vaccine,” the reviewers wrote.
Boosters have become a contentious scientific issue, with many scientists and physicians looking at the same data and reaching different conclusions. When Pfizer-BioNTech boosters were considered a month ago, the FDA’s review was neutral on whether boosters were widely needed in the general population. Outside advisers strongly rejected the idea of making them eligible to anyone 16 and older, the group that initially received the vaccines under the December authorization of vaccines.
Instead, FDA’s advisers recommended boosters of the Pfizer-BioNTech shot for people 65 and older and those at risk of serious illness, a population experts broadly agree will benefit from a third shot. They also thought people exposed to the virus on the job should be eligible. Days later, the FDA authorized the vaccine for those portions of the population.
A Centers for Disease Control and Prevention advisory committee stopped short of recommending boosters for people exposed to the virus at work. But that committee’s recommendation was overturned by the agency’s director. CDC Director Rochelle Walensky added a recommendation that people ages 18 to 64 at risk of exposure and transmission because of occupational or institutional settings may receive a booster shot.
The case for boosters relied strongly on evidence from Israel, and a representative from Israel’s Health Ministry will again testify to experts, presenting updated data. Israel used the Pfizer-BioNTech vaccine and has, since the end of August, made a third shot available to people 12 and older.