November 3, 2021

Moderna's vaccine dose is 3x higher than Pfizer's. Does that matter?

Daily Briefing

    Many people may be tempted to rank certain Covid-19 vaccines as "better" or "worse" than others, but infectious disease experts say that differences in doses—rather than the vaccine brand—could be an influential factor in protection, Rachel Gutman writes for The Atlantic.

    Your top resources on the Covid-19 vaccines

      Are some Covid-19 vaccines better—or worse—than others?

      When Covid-19 vaccines initially became available, public health leaders told people not to worry about the differences among the vaccines, saying that they were similarly protective, Gutman writes. And while all three vaccines remain highly effective at preventing hospitalization and death, a number of studies have suggested that some Covid-19 vaccines may provide better protection than others.

      For example, a CDC study found that Moderna's Covid-19 vaccine had a 95% efficacy rate against hospitalization, compared with 80% with Pfizer-BioNTech and 60% with Johnson & Johnson (J&J). In addition, a preprint study of more than 500,000 U.S. veterans found that the J&J vaccine experienced the greatest decline in protection against infection, going from 88% in March to 3% in mid-August. In comparison, Moderna's and Pfizer-BioNTech's vaccines had much smaller declines over the same time period (92% to 64% and 91% to 50%, respectively).

      The potential factors behind vaccine differences, according to experts

      However, several infectious disease experts told Gutman that the three vaccines can't be so easily compared, especially considering their differences in dosage, number of doses, dosing schedules, and more.

      "Vaccinated (and un-boosted) Americans have received 60 micrograms of Pfizer over a period of three weeks, 200 micrograms of Moderna over four weeks, or 50 billion particles of J&J in one sitting," Gutman writes. "It's apples and oranges."

      Specifically, she explained that while two of the vaccines, Moderna and Pfizer-BioNTech, use similar mRNA technology for their Covid-19 vaccines, the dosage for each vaccine is different—which experts said might account for their differences in protection over time.

      "Over time, that higher dose might be what is driving the difference in protective efficacy," said John Moore, a microbiology and immunology professor at Weill Cornell Medicine.

      Another potential contributing factor to the mRNA vaccines' differences is their dosing schedules, Gutman writes. Doses of Pfizer-BioNTech's vaccine are administered three weeks apart, while doses of Moderna's vaccine are administered four weeks apart. According to Mark Slifka, an immunologist at Oregon Health and Science University, even that one-week difference could make Moderna's vaccine more durable against the coronavirus.

      In comparison, J&J's vaccine differs substantially from Moderna's and Pfizer-BioNTech's. J&J's vaccine uses adenoviruses instead of mRNA lipid nanoparticles, and several experts said the two vaccine platforms can't really be compared directly.

      However, one factor that may explain J&J's reduced protection compared with the mRNA vaccines is the number of doses. Both mRNA vaccines are two doses, but the J&J vaccine is a single dose—although this may potentially change in the future, Gutman writes.

      As Mark Slifka, an immunologist at Oregon Health and Science University, explained, multiple doses of any given vaccine may have more import than how much of that vaccine is delivered with each dose. Receiving at least two doses "is actually the great equalizer among vaccinations," he said, because it educates the immune system on how seriously a given threat should be taken.

      And the J&J vaccine may one day be a two-dose vaccine, Gutman writes. For instance, during last month's meeting of CDC's Advisory Committee on Immunization Practices (ACIP), some committee members raised the possibility of treating an additional dose of J&J's vaccine as the second dose of a two-dose regimen instead of as a "booster."

      According to Paul Offit, director of the Vaccine Education Center at the Children's Hospital of Philadelphia, J&J's vaccine could be "every bit as good as the mRNA vaccines" if two doses are compared with two doses of mRNA vaccines.

      All 3 Covid-19 vaccines are 'somewhat interchangeable,' some experts say

      Even with the differences among the vaccines, some infectious diseases experts continue to believe all three Covid-19 vaccines are "somewhat interchangeable," Gutman writes.

      Although there are differences between J&J's adenovirus formula and Moderna's and Pfizer-BioNTech's mRNA formulas, Slifka said those differences likely do not affect the protection they provide people.

      "Both of them are nanoparticles," Slifka said. "One is a virus nanoparticle and the other one is a lipid nanoparticle, but they're both doing the same thing."

      According to Gutman, people will likely never know whether the vaccines' formulas or other factors contributed to their differences. Although large-scale studies could be conducted to determine the particular nuances among vaccine types and doses, people are unlikely to devote resources to such projects when all currently authorized vaccine regimens remain effective and millions of people have yet to receive one dose of any Covid-19 vaccine.

      Instead, Gutman writes, "For now, we'll have to keep bumbling forward with our clunky toolbox of boosters and waiting periods and half-doses—and count our blessings to live in a country where we have the luxury of asking how much vaccine is the best amount." (Gutman, The Atlantic, 10/28)

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