The much talked-up new bivalent COVID-19 vaccine boosters may not be all that superior to the old shots at neutralizing Omicron, two new studies suggest.
Both studies are small, together involving just 73 people in total who were followed for about a month. Both are pre-prints that haven’t yet been peer-reviewed. However, their authors say their findings hint at a phenomenon known as “immunological imprinting” — the immune system’s habit of locking onto, and responding to, the first version of the virus it encountered, either by vaccination or infection.
The first study comes from Columbia University and University of Michigan researchers who compared Pfizer’s and Moderna’s bivalent boosters that target both the original ancestral SARS-CoV-2 strain, as well as Omicron’s BA.4/BA.5 subvariants, against their original vaccine formulations.
After three to five weeks, post booster shot, there were no “discernibly superior” differences between the level of virus-neutralizing antibodies in the blood of people who received the revamped vaccine as their fourth shot, compared with those who received a boost with the original vaccine.
“To disappointment, the bivalent vaccine did not show superiority over the original vaccine,” co-author David D. Ho, a professor of microbiology and immunology at Columbia, told NPR.
A team from Beth Israel Deaconess Medical Center in Boston came up with similar findings. That group looked at the responses in 15 people who received the original mRNA boosters and 18 who received the tweaked, bivalent boosters. People had had two to four prior COVID-19 vaccine doses, and a third of participants had a confirmed COVID infection during the Omicron surge.
Both boosters increased antibody responses, but with only a “modest and non-significant trend” favouring the bivalent shot.
“Our findings suggest that immune imprinting by prior antigenic exposure may pose a greater challenge” than currently appreciated, the authors wrote.
A spokesperson for Pfizer Canada said the company doesn’t typically comment on pre-print studies that they weren’t involved in. Pfizer recently shared, via press release, data that found people who received its bivalent shot showed a “substantial increase” in neutralizing antibodies against Omicron BA.4 and BA.5 in the first seven days, post booster dose.
Pfizer told National Post Thursday that it will have additional data in coming weeks.
The updated Moderna vaccine approved in Canada is different than the one tested in the two new studies. Canada’s approved version was designed to target Omicron BA.1, which BA.4 and BA.5 have since eclipsed.
In a study published in the New England Journal of Medicine involving 819 people, Moderna scientists reported that a fourth dose of their BA.1-targeting booster elicited a “superior antibody response” against Omicron than a booster dose of its older vaccine, including against the BA.4 and 5 siblings, 28 days after immunization. In a statement last week, Moderna said antibody levels remained high for at least three months.
Neutralizing antibodies are used to infer how well vaccines work, and the Columbia researchers said follow-up studies will determine if the antibody response changes over time. So far there’s little available public data on how well the revamped boosters are working in the real world at preventing severe illness and hospitalization, though immunologists expect they will help thwart severe outcomes.
“No one is saying don’t get boosted,” John P. Moore, a professor of microbiology and immunology at Weill Cornell Medicine in New York City, told the Washington Post.
“The concern that I have is if you talk up these bivalent boosters as being some kind of super strong shield … that encourages people to believe they’ve got amazingly strong protection against infection.
“My message for the general public is: Don’t drop your guard just because you’ve been boosted.”
Others are concerned the new research could further dampen the less-than-enthusiastic uptake of the reworked vaccines.
“For those who are saying, ‘See, see, I told you so,’ I would say, let’s stand down a little bit and wait for some cleaner data to come out, because these studies can’t be used to support really one argument or another,” Dr. Deepta Bhattacharya, a University of Arizona professor of immunology, told NPR.
Dr. Eric Topol, a professor of medicine at Scripps Research, raised concerns about imprinting in August. Millions of people have already had three, even four shots of the original vaccines, “so there’s a potential for imprinting,” he wrote — “a preferential revving up of the immune response to whatever the person was originally exposed to.”
“Bottom line,” Topol tweeted this week: “Until more data are available, regard the bivalent booster as equivalent to a booster which augments and broadens immunity, without specific anti-BA.5 properties.”
In most provinces, immunity isn’t as high as it could be, and health officials are recommending people, 12 and older, get a fall booster dose, regardless of how many they’ve received, three to six months after their last vaccine or infection.
