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Omicron boosters not much better against variants than the originals, say two small studies

Both Moderna and Pfizer’s new vaccines increased antibodies, but researchers said the difference was not significant.

A syringe filled with COVID-19 vaccine is prepared for injection.Rogelio V. Solis/Associated Press

Omicron-specific booster shots from Moderna and Pfizer weren’t significantly better than the original COVID-19 boosters from both drug companies in two small studies that compared how they fared against the most common variants circulating in the United States.

Both the original and latest boosters caused antibodies in the human body to surge to fight off the dominant coronavirus variant, BA.5. The newer shots performed marginally better, but researchers said it probably wouldn’t make a difference.

The studies by researchers from Beth Israel Deaconess Medical Center, Columbia University, and the University of Michigan are the first to compare the original messenger RNA boosters against the newly authorized “bivalent boosters” in human blood samples. Bivalent boosters, which also rely on mRNA technology, target the original strain and the BA.4/BA.5 Omicron variants.


Federal regulators, alarmed by the spread of breakthrough COVID cases in people who received the original mRNA shots, cleared Omicron-specific boosters in the late summer based only on safety and efficacy data in animals, in what was considered a controversial move. But uptake of the new boosters has been slow. According to the Centers for Disease Control and Prevention, only about 19.4 million Americans, or nearly 6 percent of the US population, have received a bivalent booster since they were approved on Aug. 31

“People should realize that the monovalent vaccines that they were getting were already excellent at preventing severe disease, which was the goal,” said Dr. Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia who wasn’t involved in the studies but read them on a pre-print server. “The hope was that you’d have even better protection against severe disease with the bivalent booster. Given these data, it doesn’t look like that hope is going to be realized.”

Offit, a member of an independent panel of scientific advisers to the US Food and Drug Administration that voted on June 28 to recommend the agency clear the Omicron-specific boosters, was among two panelists who voted “no.” He said at the time that he was concerned about the lack of clinical data and wasn’t convinced that the new booster was better.


The Beth Israel study compared the immune responses in blood samples taken from 15 people who received the original booster with 18 people who received the bivalent booster. Both the new and old booster shots raised antibody levels against BA.5. The new booster led to 30 percent higher antibody levels, but that difference was “modest and nonsignificant,” said the study, which was posted Tuesday.

Specialized immune cells called T cells increased only modestly after people got the original or revamped boosters. The overall trend involving immune cells and antibodies was similar regardless of whether people got Pfizer or Moderna boosters.

This photo shows a vial of the Moderna Covid-19 vaccine, Bivalent, at AltaMed Medical clinic in Los Angeles, California, on October 6, 2022. RINGO CHIU/AFP via Getty Images

“It’s well known that these bivalent boosters were rolled out in the absence of any clinical trials,” Dr. Dan Barouch, who runs Beth Israel’s Center for Virology and Vaccine Research and oversaw the study, said in an interview. “Both the monovalent and bivalent boosters work. But there is no evidence that the bivalent booster works better than the monovalent booster against BA.5.”

Barouch helped create a one-dose Johnson & Johnson vaccine against COVID that was approved after the mRNA vaccines got cleared. It ended up playing only a modest role in the US response to the pandemic.

A Moderna spokesman said the Cambridge-based drug firm expects to have results of the company’s own analysis of how well its bivalent vaccine performs against BA.4/BA.5 later this year and had no comment “on research we were not involved in.”


Dr. David Ho’s lab at Columbia University and Aubree Gordon’s lab at the University of Michigan compared antibodies in blood samples from 19 people who received the original boosters with antibodies in 21 people who received the new boosters.

In their study, which was posted on a server on Monday, the Omicron booster triggered 20 percent higher antibody levels to BA.4/BA.5 than the original booster. “To some extent, we were surprised,” Ho said. “I don’t think 20 to 30 percent more antibodies would make much of a clinical difference.”

Both studies have limitations, including the small number of people tested and the lack of long-term follow-up. Both groups measured antibodies about three to five weeks after people received booster shots. “With time or maybe a second bivalent booster there could be a difference, but we would need to do those studies,” Ho said. “The new vaccine is certainly not worse, and may prove to be better with time, but we have to wait and see.”

Pfizer declined to comment on the study. Earlier this month, Pfizer said in a press release that the bivalent booster spurred a “substantial increase” in antibodies targeting BA.4/BA.5 one week after vaccination and that the shot “is anticipated to provide better protection” against those viruses than the original one. The firm plans to share additional data in the coming weeks.


Dr. David Hamer, an infectious diseases doctor at Boston Medical Center, was disappointed in the results of the studies and said they indicate that COVID booster shots didn’t need to be updated.

“The FDA may need to reconsider their approach to how they evaluate novel boosters,” he said.

Larissa Thackray, an infectious diseases biologist at Washington University School of Medicine in St. Louis, said larger studies may find that 20 to 30 percent higher antibody levels are significant. But, she said, vaccine makers should focus on developing next-generation COVID vaccines that spur broader and longer-lasting immunity, rather than updating the vaccine to match each new variant.

Jonathan Saltzman can be reached at jonathan.saltzman@globe.com. Ryan Cross can be reached at ryan.cross@globe.com. Follow him on Twitter @RLCscienceboss.