A new preprint study published in medRxiv suggests mRNA vaccines' efficacy against infection—particularly the Pfizer-BioNTech vaccine—has dropped significantly since the delta variant became widespread, although the vaccines' protection against hospitalization and death remain strong.

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Study details

For the study, researchers at Mayo Clinic and nference assessed adult patients at the Mayo Clinic Health System or affiliated hospitals in Arizona, Florida, Iowa, Minnesota, and Wisconsin who had taken at least one PCR test for SARS-CoV-2; received at least one dose of either Pfizer-BioNTech's or Monderna's Covid-19 vaccines after Dec. 1, 2020, but prior to July 29, 2021; and who did not test positive for infection before receiving an initial vaccine dose.

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Then, to determine vaccine efficacy, the researchers paired demographically and "clinically similar" unvaccinated people, people vaccinated with the Pfizer-BioNTech vaccine, and people vaccinated with the Moderna vaccine by sex, race, ethnicity, residence, PCR testing history for the coronavirus, and date of vaccination. Overall, according to the researchers, the study involved 43,895 of these "matched triples" groupings.

Key findings

The researchers found that overall, Pfizer-BioNTech and Moderna were highly effective against infection (76% and 86%, respectively) and hospitalization (85% and 91.6%, respectively) from January to July in Minnesota.

However, during the month of July, the vaccines' efficacy against infection appeared to decline in Minnesota, where the prevalence of the delta variant had increased from 0.7% in January to 70% in July. Specifically, the researchers found that during July, the Moderna vaccine appeared to have an estimated efficacy of 76% against infection, while the Pfizer-BioNTech vaccine had an estimated efficacy of 42% against infection.

Data from Florida similarly showed a lower risk of infection among individuals vaccinated with the Moderna vaccine compared to those vaccinated with the Pfizer vaccine, as did data from a matched cohort from several states.

However, the researchers said they did not find any clinically significant distinctions in the complication rate in breakthrough cases from either vaccines. Both vaccines had similar 21-day hospitalization rates, 21-day ICU admission rates, and 28-day mortality rates.

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Researchers caution against conclusions

The researchers noted that while they "observed a pronounced reduction in the effectiveness of [the Pfizer-BioNTech vaccine] coinciding with the surging prevalence of the delta variant in the United States, … this temporal association does not imply causality."

However, Venky Soundararajan, a lead author on the study, said based on the data compiled so far, the vaccines' reduced efficacy likely stems from "a combination" of both reduced efficacy over time and reduced efficacy against the delta variant. "The Moderna vaccine is likely—very likely—more effective than the Pfizer vaccine in areas where delta is the dominant strain, and the Pfizer vaccine appears to have a lower durability of effectiveness," he said.

That said, the researchers cited several limitations to their study, including that as the cohorts were not geographically representative, they cannot be generalized to the population overall. Moreover, the researchers said vaccine efficacy could have been affected by other, unknown factors not accounted for in the study.

The researchers called for additional research, particularly a comparison of each vaccine's neutralizing antibody titers and larger-scale studies with more diverse participant populations.

'A wakeup call'

According to Axios, a senior official in the Biden administration said the findings were alarming. "If that's not a wakeup call, I don't know what is," the official said.

However, other public health experts cautioned against rushing to conclusions, especially considering it is a preprint study. "This is the kind of surprising finding that needs confirmation before we should accept its validity," John Moore, a virologist at Cornell University, said.

Separately, in a statement, Pfizer said it and BioNTech "expect to be able to develop and produce a tailor-made vaccine against that variant in approximately 100 days after a decision to do so, subject to regulatory approval." (Owens, Axios, 8/11; Walker, MedPage Today, 8/10; Reuters, 8/10)