A new study published in the New England Journal of Medicine (NEJM) is the first to pit Moderna and Pfizer’s mRNA COVID-19 vaccines against each other in an efficacy face-off. The novel research compared health records from nearly half a million US veterans and found both vaccines are incredibly effective but Moderna’s candidate is marginally better at preventing COVID-19 infections, both mild and severe.
In late 2020, as Phase 3 trial data emerged, it became clear Moderna and Pfizer’s mRNA COVID-19 vaccines were incredibly effective. Across clinical trial and real-world data, the vaccines consistently prevented symptomatic COVID-19 at rates higher than 90 percent.
In the absence of a direct head-to-head clinical trial it has been unclear which mRNA vaccine is generally more effective. So this new study set out to fill that gap in the science by retrospectively analyzing health records from the Department of Veterans Affairs, the largest integrated health care system in the US.
From a database of over three million veterans, the researchers generated two cohorts of 219,842 subjects. Each person was matched with a demographically similar partner based on characteristics such as age, race, and sex. The only difference between the individuals in each matching couple was the mRNA vaccine they were administered.
Overall, the results reveal both vaccines are powerfully effective at preventing SARS-CoV-2 infections, hospitalizations and death. But Moderna’s mRNA was found to be ever-so-slightly better on all counts.
The initial 24-week study period, a snapshot of a time early in 2021 before the Delta variant emerged, revealed 4.52 positive cases of COVID-19 per 1,000 persons in the Moderna group. This compared to 5.75 cases per 1,000 persons in the Pfizer group. This means those Pfizer subjects were 27 percent more likely to report a documented COVID-19 infection.
A secondary analysis was conducted with a smaller cohort of subjects spanning a period later in the year when the Delta variant was predominant. Both vaccines were still incredibly effective in the face of the Delta variant, however, Pfizer again was marginally less effective, with its caseload rising to 6.54 more positive Delta cases per 1,000 persons compared to Moderna's per 1,000 caseload.
“Given the high effectiveness of both vaccines, either one is strongly recommended to any individual offered the choice between the two,” notes first author on the study, Barbra Dickerman. “However, this large-scale study allowed us to detect subtle differences between these two highly effective vaccines. While the identified differences in estimated risk were small on the absolute scale, they may be meaningful for larger decision-making bodies, such as health care systems and higher-level organizations, when considering the large population scale at which these vaccines are deployed.”
Exactly why Moderna’s mRNA COVID-19 vaccine is slightly more effective than Pfizer’s is a big unanswered question. Fundamentally, both vaccines are incredibly similar, delivering mRNA encoding the same SARS-CoV-2 spike protein. The researchers point to a few small but key differences between the two vaccines that could account for the discord in effectiveness.
“A difference in effectiveness between the BNT162b2 [Pfizer] and mRNA-1273 [Moderna] vaccines might be the result of the different mRNA content of the vaccines (100 μg for mRNA-1273 vs. 30 μg for BNT162b2), the different interval between the priming and boosting doses (4 weeks for mRNA-1273 vs. 3 weeks for BNT162b2), or other factors, such as the lipid composition of the nanoparticles used for packaging the mRNA content,” the researchers speculate in the study.
One factor this new study did not investigate is the difference in reported side effects between the two vaccines. While serious adverse effects from both mRNA vaccines are very rare, prior research has indicated Moderna’s vaccine can lead to higher rates of mild side effects following vaccination compared to Pfizer.
In an editorial accompanying the new study, NEJM editors Eric Rubin and Dan Longo say the most important point in the research is that both vaccines are highly effective, and the real difference in efficacy between Moderna and Pfizer is tiny. Echoing Dickerman’s advice, Rubin and Longo suggest either vaccine would be a good choice for most individuals.
“So the lesson we take away is not about differences – it’s about similarities,” write Rubin and Longo. “We are lucky to have such good options. Vaccination with any vaccine is far better than remaining unprotected. The message is that the best vaccine is the one that’s available.”
The new study was published in The New England Journal of Medicine.
Source: Harvard University
