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Despite limited available data, an FDA advisory panel recommended a booster dose of Johnson & Johnson's COVID-19 vaccine for all individuals who received the single-dose vaccine, to be given at least 2 months after the initial dose.

The FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 19-0 that the booster dose at this interval was safe and effective for individuals ages 18 and up who received the Johnson & Johnson vaccine under emergency use authorization (EUA).

VRBPAC declined to vote on booster doses given at least 6 months from the initial dose, stating that it would be unlikely any adverse events (AEs) would arise at 6 months, but not at 2 months, and that the 6-month data presented by the sponsor was only from 17 people. FDA conducted an independent assessment of the immunogenicity of this 6-month booster data, from the study, which involved healthy adults ages 18-55.

Johnson & Johnson submitted a post-hoc analysis, which showed that geometric mean titer ratios were "above the FDA-recommended non-inferiority criteria (lower bound of 95% CI >0.67)." FDA staff, however, noted the small number of participants and said the low sensitivity of the assay might be a confounder.

VRBPAC members took issue with the lack of independent verification by the FDA, but Doran Fink, MD, PhD, said the agency "recognized there was intense public interest and a sense of urgency in providing options for a second dose."

Fink said that an advisory committee meeting was scheduled and the sponsor was asked to provide data. However, instead of providing immunogenicity data for a few hundred people, as Pfizer and Moderna had done, Johnson & Johnson submitted four trials consisting of thousands of people.

Peter Marks, MD, PhD, director of FDA's Center for Biologics Evaluation and Research, said it would've taken FDA staff "months" to pore through "such a tremendous amount of data."

VRBPAC Acting Chair Arnold Monto, MD, of the University of Michigan, agreed.

"There is a public health imperative here, because what we're seeing is a group with overall lower efficacy than we've seen with mRNA vaccines, so there is some urgency to do something," he said.

Amanda Cohn, MD, of the CDC, noted that prior data presented by the agency indicated that the Johnson & Johnson vaccine was only 68% effective against hospitalization among adults ages 18 and up with no immunocompromising conditions.

Marks even took the time to put up a special slide from New England Journal of Medicine research that showed the vaccine was 20-25% less effective than its mRNA counterparts.

In explaining her vote, Oveta Fuller, PhD, also of the University of Michigan, echoed the public health urgency of an additional dose.

"In spite of the fact that I'd like to see some more data, I think the greater cause is more important," she said.

While VRBPAC voted on the booster option, many members thought that given the lower real-world efficacy of the single dose, the vaccine should be a two-dose series.

Paul Offit, MD, of the Children's Hospital of Philadelphia, said that given that Johnson & Johnson was already conducting a two-dose trial in the winter, this vaccine was "always a two-dose vaccine and it's hard to recommend it as a single-dose vaccine."

FDA staff found no new safety concerns in any of the studies, but were unable to independently verify any of the safety data. They noted more frequent tinnitus, thromboembolic events, and seizures in the vaccine arm versus placebo, and out of 19 vaccine-related AEs, nine were possible thromboembolic events.

Michael Kurilla, MD, PhD, of the NIH, said the safety data were "more than adequate for a 2-month boost" and that he would be "inclined to consider this a two-dose vaccine" going forward.

Marks said the FDA would take the idea of "an additional dose" rather than "a booster dose" under advisement.

In addition, the committee also heard data about "mix and match" booster dosing from a preprint published on Wednesday, showing heterologous boosters were safe and produced increases in immune response. The FDA asked VRBPAC to discuss what additional data were needed to make a decision on these boosters.

Some committee members were satisfied with the current data, while others were concerned about the differing age recommendations for boosters, where mRNA boosters are recommended only for certain populations and the Johnson & Johnson boosters are now recommended for adults ages 18 and up who received the one-dose vaccine.

"We have to make sure that we don't confuse the public more than we have already," said Jeannette Lee, PhD, of the University of Arkansas for Medical Sciences in Little Rock, adding that it might be "very, very messy in terms of messaging."

Monto agreed, noting that the general population has a "cut-off," where only certain adults younger than age 65 can get an mRNA booster, and the CDC's Advisory Committee on Immunization Practices (ACIP) is "restricted in doing anything until" there is an EUA.

He asked if there was a way to "get a little more flexibility about going down in age, should we see dramatically more breakthrough infections," potentially down to age 40.

Marks characterized the real-world Israeli data presented Thursday that showed a booster dose of Pfizer prevented severe disease in age 40 and up as "compelling," but that the data are not there for those younger than age 40.

If the FDA was to make a recommendation in the EUA for ages 40 and up, then ACIP could narrow that how they saw fit, he noted.

Cohn discussed the practical implications of adding language about heterologous boosters, such as that a pharmacy going into a nursing home to vaccinate residents would have to bring only one vaccine.

Monto also suggested that with reports of waning vaccine immunity, many people may be getting unauthorized booster doses anyway.

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