White House still expects new COVID boosters will offer better protection, but two new studies cast doubt

The White House’s top COVID-19 official says he still expects the protection against the Omicron BA.5 variant offered by the new COVID vaccine boosters will be better than their predecessors, despite two studies that appear to question that assumption. In an interview with CBS News, Dr. Ashish Jha also said he does not think another imminent change to the COVID boosters will be needed.

Jha’s comments come after researchers found, in two smaller groups of volunteers, data suggesting that the updated boosters provide only similar but not superior antibody boosts against BA.5, compared to the original vaccine formula.

“I do think that the protection against infection is going to be better than if you were getting the original prototype booster,” Jha told CBS News.

Jha said he was not surprised about the new study results and praised the two scientists — Dan Barouch of Harvard Medical School and David Ho of Columbia University — who led each of the research teams behind the preliminary findings.

However, he predicted that the “well-controlled trials” with “larger samples” now underway from vaccine makers could yield more favorable results about the boosters’ performance. 

The studies did turn up higher antibody responses after the updated booster, Jha said, even if they were too small to be statistically significant.

“I expect we’re going to see at least that size benefit, probably bigger, in the Pfizer and Moderna studies,” Jha said.

Jha’s comments are in line with expectations previously voiced by federal health officials from across the Biden administration, who have argued for months that the updated boosters being rolled out this fall would outperform the original formulations.

The new boosters are known as “bivalent” because they include both a component targeting the original “prototype” strain and another aimed at the BA.4 and BA.5 variants.

Early data from animals tested with the new shots had been promising. Previous versions targeting other strains trialed on humans also suggested a bivalent formulation would also offer at least an “incremental” improvement, health authorities concluded.

And with new strains on the rise in the U.S. and around the world, officials hoped the new vaccines would do better at fending off a feared winter surge of the virus.

“The one I am paying most close attention to in the United States is BQ.1.1, which is a BA.5 derivative, and based on all of the things that we understand about immunology, your protection against BQ.1.1 is going to be significantly better after a BA.5 bivalent [booster],” said Jha. 

“Modest and nonsignificant”

But this week, two studies seemed to upend those expectations.

“There was no significant difference in neutralization of any SARS-CoV-2 variant tested between individuals who received a fourth monovalent vaccine and those who received a fourth dose of a bivalent vaccine,” concluded one study, which has yet to be peer-reviewed, posted by the team led by Ho.

Scientists drew blood from people roughly a month after they had gotten the new shot and tested their antibody responses against 
“pseudoviruses” — essentially mock-ups of different variants, including BA.5. 

Barouch’s team performed a similar experiment against BA.5. They turned up only “a modest and nonsignificant” improvement from the updated boosters in their study, which has also yet to be peer-reviewed.

“If that very small difference holds up in a much larger study, then a much larger study might actually say that’s a statistically significant difference. The question is, is it clinically relevant? And I don’t believe that that level of difference is clinically relevant,” Barouch said in an interview.

Barouch said a phenomenon called immune imprinting may turn out to be the culprit for the disappointing immune response to the updated booster. 

Immune imprinting, also known as “original antigenic sin,” refers to the theory that the initial exposure people had to an earlier strain of the virus — either from infection or vaccination — may hinder the ability of the body to produce antibodies to new strains.

Both the vaccine companies and health officials had previously downplayed the hurdle this phenomenon might pose to the new shots. 

Barouch acknowledged there was a possibility that responses against BA.5 could improve after more weeks following the updated booster, but cautioned that we have seen antibodies decline in the months after previous mRNA COVID shots.

His team also measured another part of the immune response from T cells. Those were “not substantially” boosted by additional shots from either the bivalent or original formulations.

“We all talk about antibodies, the focus has been on antibodies, but there’s two sides to the immune system: antibodies and T cells. And we believe that both are important for protection against severe disease,” said Barouch.

Updating the vaccines

The new studies come as the Biden administration is preparing for key decisions about the country’s COVID-19 vaccine supply.

Millions of doses of the original monovalent vaccine, which is still being used for primary series shots, are due to expire over the coming months. Boosters also still need to be greenlighted for the youngest age group: children down to 6 months old.

The federal government’s supply of the updated boosters is on pace to run out next year as a result of a stalled COVID funding request on Capitol Hill, which will prompt a shift to the private market.

FDA and CDC officials have said that they expect to decide over the winter whether and how to update the vaccine regimen for the future.

Those decisions will rest, in part, on how the updated shots perform.

“We will have our BA.4/5 data by year end and ours will be statistically powered,” Moderna spokesperson Chris Ridley said in an email.

Ridley also pointed to results from a previous bivalent formulation by Moderna targeted at the BA.1 variant, which was published in The New England Journal of Medicine a few weeks ago. 

Pfizer and their German partner BioNTech announced finding “positive early data” from their updated shots earlier this month. Pfizer spokesperson Steve Danehy said they expect to “have additional data in coming weeks” on the shots.

“We’re going to want to make policy decisions based on more definitive, larger studies, which are coming soon,” Jha said.