FDA sees limits to omicron-booster studies from Columbia, Harvard

The Food and Drug Administration said two studies this week showing that the new omicron boosters weren’t that much better than the old shots were too small to come to any real conclusions.

Scientists at Columbia and Harvard, in two independent studies, found the new boosters and the old shots basically performed the same against omicron BA.5, raising doubts about whether the vaccines will live up to high expectations set by the Biden administration. The antibody responses were slightly higher with the omicron boosters, though the studies concluded the difference wasn’t significant.

Dr. Peter Marks, head of the FDA’s vaccine division, said the studies are small and subject to limitations. Data from larger well-controlled studies are expected in the near future, he said. Pfizer and Moderna are conducting clinical trials on the new boosters and are expected to provide data later this year.

“It is important to note that even the data from these initial small studies indicate that the bivalent vaccines are generally at least as good or better as the original vaccines in generating an immune response, particularly to BA.4/BA.5 and other newer variants,” Marks said in a statement.

Even modest increases in immune response could have positive consequences for public health, he added.

“FDA continues to encourage eligible individuals to consider receiving an updated vaccine to help protect against the currently circulating Covid-19 variants and the wave of Covid-19 that appears to be coming,” Marks said.

Top U.S. health officials have said the new boosters should perform better because they are now matched to the dominant circulating strain, omicron BA.5, for the first time since the pandemic began as well as the original strain of Covid that emerged in China. These are called bivalent shots.

The old shots, called monovalent, were designed against the first strain of Covid. Their effectiveness has declined over time as the virus has mutated away from the original strain.

“It is reasonable to expect based on what we know about immunology and the science of this virus that these new vaccines will provide better protection against infection, better protection against transmission and ongoing and better protection against serious illness,” Dr. Ashish Jha, head of the White House Covid task force, told reporters in September.

The Columbia and Harvard studies clearly demonstrate that the boosters work, but it’s still an open question whether they’re going to do a much better job preventing disease, particularly infection and mild illness, than the old shots.

“The take-home lesson is the people who were in high risk groups and benefit from booster doses as we enter this late fall and early winter — those who are immunocompromised, who have high risk medical conditions, who are elderly — they should get this booster dose,” said Dr. Paul Offit, a member of the FDA’s independent vaccine advisory committee.

But Offit said public health officials should be cautious about overselling the shots as a major upgrade.

“We have to be careful when we get in front of the American public and try and sell this vaccine as something that’s significantly better when all the evidence we have so far doesn’t support that,” said Offit.

The Columbia study looked at 21 people who received the new booster while the Harvard study looked at 18 who got the new shot. Both studies are preprints, which means they haven’t undergone peer review by others in the field.

The Columbia study found that antibody levels were about 1.2 times higher with a bivalent booster compared with a fourth dose of the monovalent shots, while the Harvard study found they were 1.3 times higher. Though the antibody levels were slightly higher with the bivalent booster, the studies both concluded the difference was not significant.

Dr. Dan Barouch, the lead author of the Harvard study, acknowledged that the preprints are small but emphasized that they were conducted independently and basically came to the same conclusion, which is noteworthy.

“It’s important to note that the two studies were done independently. They’re small studies but there are two of them — it’s not just a fluke,” said Barouch, whose lab played a pivotal role in the development of the Johnson & Johnson Covid vaccine.

Dr. Peter Hotez, co-director of vaccine development at Texas Children’s Hospital, said the studies were conducted by two of the best virology labs in the country and the methodology was sound. Still, the findings should be viewed as preliminary until more data comes in, Hotez cautioned.

“We have to be careful not to draw too many conclusions from it,” said Hotez, who also co-led a team that developed a patent-free vaccine called Corbevax that India authorized for use last December.

The studies are of public interest because there’s very limited human data on how the omicron BA.5 boosters perform right now. The FDA authorized the shots in September based on clinical trial from a similar shot developed against the first version of omicron, BA.1.

Pfizer and Moderna were originally developing their new boosters against BA.1, but the FDA asked the companies to switch gears over the summer and target BA.5 instead because that subvariant had become dominant. As a consequence, there wasn’t enough time for Pfizer and Moderna to run clinical trials and present direct human data on the shots before authorization.

The FDA also looked at data directly on the BA.5 shots that came from animal studies. The agency was acting urgently to get the shots out by the fall in the hope they’d do a better job heading off a Covid wave.

But new subvariants are also now gaining ground in the U.S., particularly BQ.1 and BQ.1.1, which now represent about 27% of new infections. It’s unclear how the boosters will perform against these subvariants. Health officials expect the shots to continue to provide protection because the subvariants are descended from BA.5.