Two new studies paint encouraging picture of Covid-19 vaccine’s performance

Two new studies published Wednesday report good news about the updated Covid-19 vaccine, with one suggesting it is more effective than the previous monovalent vaccine and the other showing that even though it targeted an earlier strain of the SARS-CoV-2 virus, its protection is holding up against current variants.

The findings suggest the updated vaccine, which targets both the original SARS-2 virus and the Omicron subvariants BA.4 and BA.5, is performing better than some critics of the decision to update the vaccine concluded, based on studies that only compared the levels of neutralizing antibodies each induced.

The first study, published in the New England Journal of Medicine, found the updated vaccine was significantly more effective at protecting against severe illness, hospitalization, and death from Covid than the monovalent vaccine that was previously used.

“It’s clear from this study that the bivalent booster, in that short term following administration, provides additional protection above and beyond that of the monovalent,” said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy. “I think that’s clear and this should be a reason why we can feel confident that it was the right decision to go with the bivalent vaccine.”

Anna Durbin, director of the Center for Immunization Research at the Johns Hopkins Bloomberg School of Public Health, agreed.

“I think it’s pretty compelling,” said Durbin. “It certainly is a big difference between the two.”

The research was conducted by scientists at the University of North Carolina Gillings School of Global Public Health and the North Carolina Department of Health and Human Services, using state vaccine registry data. The senior author, Danyu Lin, said this is the first study that estimated vaccine effectiveness of the updated vaccine in comparison to the previous product. (Lin, a professor of biostatistics, spells his given name Dan-yu when he publishes in the scientific literature.)

Determining whether the bivalent vaccine is more effective than the previous single-strain version has been difficult. When it authorized the updated vaccine the Food and Drug Administration rescinded the license for the monovalent vaccine, a move that closed the door to head-to-head trials. Testing the two vaccines at the same time would have generated the best picture of how the new vaccine stacked up against the one it replaced.

Lin and his colleagues did the next best thing, comparing the vaccine effectiveness of the monovalent virus over 99 days from late May 2022 to the end of August, to the vaccine effectiveness of the bivalent vaccine over 99 days from September through late November. In the earlier period, nearly 300,000 people received a monovalent booster dose, while just over 1 million received the bivalent booster and were followed in the later period.

For people aged 12 and older who received the monovalent vaccine, the vaccine effectiveness against disease severe enough to require hospitalization was 25%. The effectiveness of the bivalent vaccine was 58.7%. Vaccine effectiveness against severe infection that resulted in hospitalization or death was 24.9% for the monovalent booster and 61.8% for bivalent booster.

Of note, two new Omicron subvariants, BQ.1 and BQ.1.1, began to circulate after the bivalent vaccine went into use. Given the bivalent vaccine targeted a different version of Omicron, that could have rendered the updated vaccine less effective.
“You would expect that will make the bivalent booster even worse, because the bivalent booster is targeting BA.4 and BA.5,” Lin told STAT. Instead, the study findings suggested the updated vaccine was more effective, both against the earlier BA.5 subvariant and the BQ strains that followed.

“I think it’s pretty convincing,” Lin said.

The second study released Wednesday looked at whether protection generated by the bivalent booster was still effective against the newest Omicron subvariants that are sweeping the country, XBB.1 and XBB.1.5. It was conducted by scientists from the Centers for Disease Prevention and Control.

They reported in the CDC journal Morbidity and Mortality Weekly Report that the bivalent vaccine’s effectiveness against the XBB and XBB.1.5 strains is similar to what was seen when the BA.5 strain of the virus was circulating.

Early studies measuring neutralizing antibody responses to the new XBB subvariants raised concerns that the mutations contained in the new strains would further erode the protection generated by the vaccine. But that does not appear to be playing out in the real world, the CDC scientists suggested in a media briefing.

“So bottom line … is we did not see reduced vaccine protection against symptomatic illness for XBB and XBB.1.5, compared with those other recent BA.5 variants,” said Brendan Jackson, who currently heads CDC’s Covid response.

“Quite reassuring.”

The article looked at data from Covid tests conducted at pharmacies during the period from Dec. 1, 2022, to Jan. 13. It found that vaccine effectiveness against symptomatic infection was quite similar. For people aged 18 to 49, the effectiveness was 49% for XBB and XBB.1.5 viruses versus 52% for the BA.5 viruses. For those aged 50 to 64, the effectiveness against the XBB-related strains was 40%, compared to 43% for BA.5. And for people aged 65 and older, the effectiveness against infection by XBB and XBB.1.5 viruses was 43%, compared to 37% against the BA.5 viruses.

The estimates were calculated by comparing infections in people who had received a bivalent booster between two and three months earlier against people who had not received the updated booster.

Jackson said additional data the CDC was posting to its website on Wednesday showed that people who got the updated booster have a 13-fold reduction in the risk of death compared to people who are unvaccinated. People vaccinated with the bivalent booster had more than a two-fold reduced risk of death from Covid compared to vaccinated people who had only received monovalent vaccine.

The authors noted several possible limitations of the study, including the fact that the number of previous vaccinations and infections among participants was based on self-reported data. If there had been more infections among the participants than reported — likely, given that Covid can cause very mild and even asymptomatic illness — that could have the effect of making the vaccine look less protective than it actually is. That’s because infection also confers some protection, albeit of limited duration, against infection.

“So, if anything, these estimates that we’re publishing are probably underestimates of how well that vaccine is protecting,” said Ruth Link-Gelles, lead author of the study.

This article was updated to include the findings of the study published in the New England Journal of Medicine.