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September 23, 2021

Why might one Covid-19 vaccine outperform another? Here's the science behind the potential 'efficacy gap.'

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    CDC on Friday published research that found the efficacy of Pfizer-BioNTech's Covid-19 vaccine against hospitalization fell from 91% to 77% four months after the second shot, while Moderna's Covid-19 vaccine showed no decline in efficacy in the same time period—findings that indicate the Moderna vaccine may offer more protection over time, Apoorva Mandavilli writes for the New York Times

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      A burgeoning efficacy gap

      According to the Mandavilli, around 221 million doses of the Pfizer-BioNTech vaccine and about 150 million doses of the Moderna vaccine have been dispensed in the United States since the two mRNA vaccines were authorized.

      Since that time, federal officials have suggested they're equally effective. Initial clinical trials, for instance, suggested both vaccines had remarkably similar efficacy against symptomatic infection: 95% for Pfizer and 94% for Moderna.

      However, subtle differences in efficacy have emerged over time, Mandavilli writes. According to Mandavilli, a half-dozen studies published over the past few weeks suggest that Moderna's vaccine provides more long-term protection than Pfizer-BioNTech's vaccine.

      "Our baseline assumption is that the mRNA vaccines are functioning similarly, but then you start to see a separation," Natalie Dean, a biostatistician at Emory University, said. "It's not a huge difference, but at least it's consistent."

      That said, researchers caution that the vaccines have never been directly compared in an appropriately designed study, so most of these differences are based on observational data. Moreover, Dean said the results of these studies demonstrating a difference between the two vaccines can be skewed by several factors, such as location, patient age groups, dose timing, and time of vaccination.

      For instance, Pfizer-BioNTech's vaccine was available to priority groups—specifically older adults—weeks before Moderna's. As a result, because immunity wanes more quickly in older adults, an observed decline in a group of primarily older adults could give a false impression that protection from the Pfizer vaccine dissipates quickly, Mandavilli writes.

      Citing how those factors could influence the results, Bill Gruber, an SVP at Pfizer, said, "I'm not convinced that there truly is a difference." Gruber added, "I don't think there's sufficient data out there to make that claim."

      However, most researchers and scientists perceive a slight but persistent gap in efficacy based on results from observational studies conducted in multiple locations, including Qatar and Minnesota. According to Mandavilli, Moderna's efficacy against severe illness in those studies ranged from 92% to 100%—and Pfizer-BioNTech 's numbers trailed by about 10 to 15 percentage points. 

      In addition, while experts have noted that protection waned over time in both vaccines, even more so with the arrival of the delta variant, two recent studies indicate the Moderna vaccine was better at preventing illness by more than 30 percentage points.

      Further, some studies found that the Pfizer-BioNTech vaccine produced roughly one-third to one-half of the antibodies produced by the Moderna vaccine—although John Moore, a virologist at Weill Cornell Medicine in New York, explained that decrease is trivial. "For comparison, there is a more than 100-fold difference in the antibody levels among healthy individuals," Mandavilli writes.

      Potential effects of an efficacy gap

      "At the end of the day, I do think there are subtle but real differences between Moderna and Pfizer," said Jeffrey Wilson, an immunologist and physician at the University of Virginia who co-authored a study published in JAMA Network Open this month that compared antibody response between vaccines. "In high-risk populations, it might be relevant. It'd be good if people took a close look."

      That's because the difference could influence the ongoing debate about booster shots, particularly as federal agencies evaluate the need for a third shot of the Pfizer vaccine, specifically for some high-risk groups, writes Mandavilli.

      And while researchers say they do not yet know what might account for the difference, they cited several potential factors, such as the difference in dosing—Pfizer-BioNTech offers a 30-microgram dose, while Moderna offers a 100-microgram dose. Another potential factor is the timing between doses—Pfizer-BioNTech has a three-week wait period while Moderna uses a four-week period between doses.

      Both vaccines perform extremely well

      Ultimately, however, researchers generally agree that the disparity between the two vaccines is minor, and its real-world impact is uncertain, Mandavilli writes, since both vaccines provide strong protection against severe illness and hospitalization—particularly for people under 65.

      Moreover, according to Mandavilli, scientists originally hoped that the vaccines would have an efficacy of around 50% to 60%. "We would have all seen that as great result and been happy with it," Moore said. "Fast forward to now, and we're debating whether 96.3% vaccine efficacy for Moderna versus 88.8% for Pfizer is a big deal." (Mandavilli, New York Times, 9/22)

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