People who received a Johnson & Johnson coronavirus vaccine may be better off with a booster shot from Moderna or Pfizer-BioNTech, according to preliminary data from a federal clinical trial published Wednesday.
That finding, along with a mixed review of Johnson & Johnson's booster data from the Food and Drug Administration released earlier in the day, could lead to a heated debate about whether and how to offer additional shots to the 15 million Americans who have received the single-dose vaccine.
The agency's panel of vaccine advisers will meet Friday and vote on whether to recommend that the agency authorize the company's application for boosters for recipients of its vaccine.
Despite these questions about the strength of J&J boosters, some experts anticipated that the agency would clear the shots anyway to meet the public's demand. Once the agency authorized a booster from Pfizer-BioNTech last month, "the die was cast," said John Moore, a virus expert at Weill Cornell Medicine.
In a study conducted by the National Institutes of Health, researchers organized nine groups of roughly 50 people. Each group received one of the three authorized vaccines, followed by a booster. In three groups, volunteers received the same vaccine for a boost. In the other six, they switched to a different one.
The researchers found that those who got a Johnson & Johnson shot followed by a Moderna booster saw their antibody levels rise 76-fold within 15 days, whereas those who received another dose of Johnson & Johnson saw only a fourfold rise in the same period. A Pfizer-BioNTech booster raised antibody levels in Johnson & Johnson recipients 35-fold.
Still, the authors cautioned about the study's small size and noted that they did not follow the volunteers long enough to identify potential rare side effects.
The study was also limited in how it measured the immunity provided by boosters. The researchers looked only for antibodies that can stop the coronavirus from replicating in cells. They did not examine how well the booster trains immune cells to recognize and kill infected cells.
Earlier Wednesday, an FDA analysis questioned the strength of evidence Johnson & Johnson provided in its application for boosters.
A key test used by the company to measure the immune response of a six-month-boost — known as a psVNA assay — was not sensitive enough for the task, the analysis said. The agency also questioned whether the increase in immune response was as big as the data suggested.
"It is likely that the results seen are due to the low sensitivity of the psVNA assay used," the FDA stated in its report.
The FDA saw a potential improvement in protection from a J&J booster given two months after the first shot, based on a large trial sponsored by the company.
"Although not independently confirmed by FDA from datasets, summaries of the data suggest there may be a benefit in a second dose administered approximately 2 months after the primary dose," the agency said in its report.
Johnson & Johnson in a statement said it looked forward to discussing the data at the Friday meeting, where panelists will also hear a presentation from the authors of the mix-and-match study.
The FDA's discussion this week of the Johnson & Johnson vaccine has big implications for the shot's future in the U.S., said Jason Schwartz, an associate professor of health policy at the Yale School of Public Health. The vaccine was already unlikely to have much uptake in the country in the long run, he said. And if the FDA recommends a booster for Johnson & Johnson recipients of a different vaccine, he added, "it's hard to see what would steer people to the J&J vaccine."
The FDA has already authorized an additional shot of the Pfizer-BioNTech vaccine for people older than 65 or with health conditions or job exposures that put them at higher risk. Moderna has also submitted an application for a booster, which will be evaluated by the FDA's advisers Thursday. It may also win authorization, despite limited evidence that the protection provided by an initial two doses of Moderna is waning.
In its application for a booster, Johnson & Johnson included the results of a large-scale trial that began in November in which they gave half their volunteers a second dose two months after the first. The other half received a placebo.
In August, the company announced that in the portion of the trial that took place in the United States, the efficacy rose to 94%. But in its report, the FDA focused on the worldwide results in which the increase was more modest, rising to 75%.
Against severe to critical COVID-19, two shots had an efficacy of 100%. But regulators warned in the analysis posted Wednesday that there was little data from that trial on the delta variant, which now causes the vast majority of infections in the United States.
In August, when top Biden administration health officials announced plans to possibly begin administering boosters in September to Moderna and Pfizer-BioNTech recipients, they said they anticipated that those who received Johnson & Johnson's shot would also need one but that more data was needed.