Moderna vs. Pfizer: Both Knockouts, but One Seems to Have the Edge

Pfizer-BioNTech, left, and Moderna COVID-19 cans are ready for patients on March 8, 2021 at Cornerstone Pharmacy in Little Rock, Ark. (Rory Doyle / The New York Times)
It was a permanent waiver by federal health officials after the coronavirus vaccines were approved: these shots are all equally effective.
That turned out not to be true.
About 221 million doses of Pfizer BioNTech vaccine have been dispensed in the United States to date, compared with about 150 million doses of Moderna's vaccine. In half a dozen studies published in the past few weeks, Moderna's vaccine appeared to offer better protection than the Pfizer BioNTech vaccine in the months following immunization.
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A study published Friday by the Centers for Disease Control and Prevention found that the effectiveness of the Pfizer BioNTech vaccine against hospitalization decreased from 91% to 77% after four months after the second vaccination. The Moderna vaccine showed no decline over the same period.
If the effectiveness gap continues to widen, it may have repercussions on the booster debate. Federal agencies this week are reviewing the need for a third shot of the Pfizer BioNTech vaccine for some high-risk groups, including older adults.
Scientists who were initially skeptical of the reported differences between the Moderna and Pfizer-BioNTech vaccines are slowly becoming convinced that the discrepancy is small but real.
"Our basic assumption is that the mRNA vaccines work similarly, but then you start to see a separation," said Natalie Dean, biostatistician at Emory University in Atlanta. "It's not a huge difference, but at least it's consistent."
But the discrepancy is small and the real world consequences uncertain as both vaccines are still highly effective at preventing serious illness and hospitalization, she and others warned.
"Yeah, probably a real difference that probably reflects what's in the two vials," said John Moore, a virus expert at Weill Cornell Medicine in New York. "But really, how important is this difference in the real world?"
"It is inappropriate for people who have taken Pfizer to freak out that they are getting an inferior vaccine."
Even in the original clinical trials of the three eventually US-approved vaccines - made by Pfizer-BioNTech, Moderna, and Johnson & Johnson - it was clear that the J&J vaccine was less effective than the other two. Since then, research has confirmed that trend, although J&J announced this week that a second dose of its vaccine would increase its effectiveness to levels comparable to the others.
Pfizer-BioNTech and Moderna vaccines are based on the same mRNA platform and had remarkably similar efficacy against symptomatic infections in early clinical trials: 95% for Pfizer-BioNTech and 94% for Moderna. This was in part why they were described as being more or less equivalent.
The subtleties have crystallized over time. The vaccines have never been directly compared in a carefully designed study, so the data suggesting different effects are mainly based on observation.
The results of these studies can be biased by a number of factors, including the location, age of the vaccinated population, when to vaccinate, and when between doses, Dean said.
For example, the Pfizer BioNTech vaccine was launched weeks before Moderna's for priority groups - older adults and healthcare workers. Immunity declines more quickly in older adults, so a decline seen in a group consisting primarily of older adults may give the false impression that protection from the Pfizer BioNTech vaccine is waning quickly.
Given these reservations, "I am not convinced that there really is any difference," said Dr. Bill Gruber, Senior Vice President at Pfizer. "I don't think there is enough data to make that claim."
Meanwhile, however, the observational studies have provided results from a number of locations - Qatar, the Mayo Clinic in Minnesota, several other states in the United States - and from health workers, hospital veterans, or the general population.
The effectiveness of Moderna against serious illnesses ranged from 92% to 100% in these studies. Pfizer-BioNTech's numbers were 10 to 15 percentage points behind.
The two vaccines differ more in their effectiveness against infections. Protection from both waned over time, especially after the introduction of the Delta variant, but the levels of the Pfizer BioNTech vaccine fell. In two of the most recent studies, the Moderna vaccine performed more than 30 percentage points better at preventing disease.
Some studies found that the antibody levels produced by the Pfizer BioNTech vaccine were one-third to one-half of those produced by the Moderna vaccine. However, this decrease is trivial, said Moore: By comparison, there is a more than 100-fold difference in antibody levels in healthy individuals.
However, other experts said the corpus of evidence indicated a disparity worth investigating, at least in people who are poorly responsive to vaccines, including the elderly and the immunocompromised.
"Ultimately, I think there are subtle but real differences between Moderna and Pfizer," said Dr. Jeffrey Wilson, an immunologist and physician at the University of Virginia at Charlottesville, co-authored one such study. published in JAMA Network Open this month. “It could be relevant in high risk groups. It would be good if people took a closer look. "
"Pfizer is a big hammer," added Wilson, but "Moderna is a sledgehammer."
Several factors can cause the divergence. The vaccines differ in dosage and in the time between the first and second dose.
Vaccine manufacturers would normally have enough time to test a number of doses before deciding on one - and they have done such tests for their trials of the coronavirus vaccine in children.
But in the middle of a pandemic last year, companies had to guess the optimal dose. Pfizer went with 30 micrograms, Moderna with 100.
Moderna's vaccine is based on a lipid nanoparticle that can deliver the larger dose. And the first and second vaccinations of this vaccine are staggered by four weeks, compared to three for the Pfizer BioNTech vaccine.
The extra week could give the immune cells more time to reproduce before the second dose, said Dr. Paul Burton, Moderna's chief medical officer. "We need to keep studying this and doing more research, but I think it's plausible."
The Moderna team recently showed that half a dose of the vaccine was still causing antibody levels to skyrocket. Based on that data, this month the company asked the FDA to approve 50 micrograms, half the dose, as a booster dose.
There is limited evidence to show the effect of this dose and no evidence of how long the higher antibody levels could last. Federal agencies are reviewing Moderna's data to determine if the data available is sufficient to approve a booster dose of half the dose.
Ultimately, both vaccines still hold up against serious illness and hospitalization, especially in people under 65, Moore said.
Scientists had initially hoped that the vaccines would be 50% or 60% effective. "We would all have seen that as a great result and were satisfied with it," he said. "Fast forward to now and we're debating whether 96.3% of vaccine effectiveness is a big deal for Moderna versus 88.8% for Pfizer."
© 2021 The New York Times Company

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