Real-world data show updated Covid-19 boosters increase protection against infection

The updated Covid-19 boosters increase people’s protection against symptomatic infection from the coronavirus, according to some of the first estimates of how the shot is performing in the real world and in people, not just in lab experiments. What’s more, that protection was even stronger when people waited a longer period of time since their last dose of the original shot.

The findings, released Tuesday by the Centers for Disease Control and Prevention, do not, however, address the question of whether the bivalent shot offers greater protection than another shot of the original formulation would have.

Health regulators authorized an updated form of the shot for people 12 and up in September, before making children 5 and older eligible the following month. The new shots — which mark the first time the makeup of the vaccines has been changed — target both the original strain of the coronavirus and the BA.5 Omicron subvariant, which was dominant in the United States this summer. Uptake of the new shots has been slow, however, with just about 13% of adults and 30% of those over 65 receiving doses so far.

In the new report, researchers relied on a national testing program available at pharmacies to come up with estimates for the relative vaccine effectiveness of the new shots, compared to people who had been previously vaccinated but hadn’t received a bivalent booster. They also measured effectiveness based on whether people received their bivalent booster just two to three months since their last shot of the original vaccine, or eight months or more. Only adults who had Covid-19 symptoms and who did not have immunocompromising conditions were included in the analysis.

For people 65 and older, the relative vaccine effectiveness of the bivalent shot was 28% for people who had more recently had a dose of the original vaccine, and 43% for people who were at least eight months out. For people 50 to 64, the estimates of effectiveness were 31% and 48%, respectively, and for people 18 to 49, they were 30% and 56%.

“Bivalent mRNA vaccines provided additional protection against infection compared with previous vaccinations with 2, 3, or 4 monovalent vaccines alone,” the researchers wrote, noting that they saw “relative benefits increasing with increasing time since receipt of the most recent monovalent vaccine dose.”

The findings that a longer gap between doses elicited a bigger relative boost in protection suggest that the benefits of another shot are higher the longer someone is out from their last shot. Experts have also said that the immune response can deepen with time after a person’s last exposure, whether in the form of an infection or vaccine. Health officials have recommended that people wait three months since their last infection before getting boosted.

The new research relied on more than 360,000 tests performed at nearly 10,000 pharmacies.

The study period was from Sept. 14 to Nov. 11, when BA.5 and related sublineages were dominant.

The effectiveness estimates in the new report relate to just one point in time. Given that the bivalent boosters were only authorized a few months ago, researchers still can’t say how long that enhanced protection against infection will last. The mRNA vaccines’ ability to block infection wanes over a period of months, particularly as the virus evolves, which is why so many people who’ve been vaccinated and boosted have gotten infected over the past year in the age of the Omicron variant. However, the protection elicited against more serious outcomes has held up much better.

The new results can’t settle the debate among some experts about whether it was necessary to refine the shots or whether another dose of the original formulation would provide a similar boost of protection. In an effort to keep up with the SARS-CoV-2 virus’s evolution, regulators authorized the updated shots before human efficacy data were available.

Since then, researchers have been trying to compare the vaccines by examining how well the antibodies generated by the different shots stand up to different variants in simulated lab studies. A few of these “immunogenicity” studies initially suggested that the updated shots didn’t seem to provide deeper coverage than another shot of the original formulation would have provided, but other researchers have found in their experiments that the bivalent shots indeed stand up better to different forms of Omicron. Pfizer-BioNTech and Moderna have also said they’ve seen improved immunogenicity data from the updated shots that could indicate they’re more protective than the original shots against Omicron strains.

“It is clear now, despite an initial bit of confusion, that the BA.4/5 bivalent booster — what we refer to as the updated vaccine — clearly induces a better response against BA.4/5 and the sublineages of BA.4/5 than does the ancestral strain,” Anthony Fauci, the country’s top infectious disease official, said at a White House briefing Tuesday, likely his last public briefing before he leaves his government post next month after decades of service. 

The new study had several limitations. For one, people who’ve been vaccinated — particularly those who rushed out to get the bivalent booster — could have different behaviors or risk factors for contracting Covid. It also relied on people to report their infection history; it’s possible previous infections were underreported if they were mild or people didn’t get tested.

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