FDA Sees Limits to Columbia, Harvard Omicron Booster Trials

The Food and Drug Administration said two studies this week showed the new Omicron boosters weren’t much better than the old shots, too small to draw any real conclusions.

Scientists from Columbia and Harvard found in two independent studies that the new booster shots and the old omicron BA.5 shots worked essentially the same, raising doubts as to whether the vaccines will meet the Biden administration’s high expectations. Antibody responses were slightly higher with the Omicron boosters, although the studies concluded that the difference was not significant.

dr Peter Marks, head of the FDA’s vaccines division, said the studies are small and subject to limitations. Data from larger, well-controlled trials are expected in the near future, he said. Pfizer and Modern are conducting clinical studies with 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 suggest that the bivalent vaccines are generally at least as good or better than the original vaccines at eliciting an immune response, particularly to BA.4/BA.5 and other newer variants,” Marks said in a statement.

Even a modest increase in immune response could have positive public health implications, he added.

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

Senior US health officials said the new boosters should perform better as they now match 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 are. These are called bivalent shots.

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

“Based on what we know about the immunology and science of this virus, it is expected that these new vaccines will provide better protection against infection, better protection against transmission, and sustained and better protection against serious disease,” dr Ashish Jha, head of the White House Covid task force, told reporters in September.

The Columbia and Harvard studies clearly show that the boosters work, but it’s still an open question whether they will prevent disease, particularly infections and minor illnesses, much better than the old vaccines.

“The takeaway lesson is the people who have been in high-risk groups and will benefit from booster doses as we enter this late autumn and early winter – those who are immunocompromised, who have high-risk conditions, who are older – they should be getting this booster shot,” 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 go before the American public and try to sell this vaccine as something significantly better when all the evidence we have so far doesn’t support it,” Offit said.

The Columbia study looked at 21 people who received the new booster shot, while the Harvard study looked at 18 people who received the new shot. Both studies are preprints, meaning they have not been peer-reviewed by others in the field.

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

dr Dan Barouch, lead author of the Harvard study, acknowledged that the preprints were small but stressed that they were conducted independently and came to essentially the same conclusion, which is noteworthy.

“It is important to note that the two studies were conducted independently. They’re small studies, but there are two of them — it’s not just a coincidence,” said Barouch, whose lab played a crucial 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 country’s top virology labs and the methodology is sound. Still, the results should be considered preliminary pending more data, Hotez warned.

“We have to be careful not to draw too many conclusions from this,” said Hotez, who also led a team developing an off-patent vaccine called Corbevax, which India approved for use last December.

The studies are of public interest as there is very limited human data on how the omicron BA.5 boosters are currently performing. The FDA approved the injections in September based on a clinical trial of a similar injection developed against the first version of omicron, BA.1.

Pfizer and Moderna originally developed their new boosters against BA.1, but the FDA urged the companies to switch over the summer and target BA.5 instead, as that subvariant had become dominant. As a result, Pfizer and Moderna did not have enough time to conduct pre-approval clinical trials and provide direct human data on the recordings.

The FDA also directly examined data on the BA.5 shots that came from animal testing. The agency acted urgently to get the footage out by autumn in hopes they would do a better job of staving off a Covid wave.

But new subvariants are also gaining ground in the US, most notably BQ.1 and BQ.1.1, which now account for 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 as the subvariants are descended from BA.5.