Both knockouts, but one seems to have an edge

After the coronavirus vaccine was approved, it was a constant refrain from federal health authorities: all these shots are equally effective.

It turned out not to be true.

To date, approximately 221 million doses of Pfizer-BioNTech vaccine have been administered in the United States, compared to approximately 150 million doses of Moderna vaccine. In a half-dozen study published in the last few weeks, the Moderna vaccine appeared to be more protective than the Pfizer-BioNTech vaccine in the months following immunization.

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The effectiveness of the Pfizer-BioNTech vaccine for hospitalization dropped from 91% to 77% four months after the second shot, according to a study published by the Centers for Disease Control and Prevention on Friday. The Moderna vaccine did not show a decrease during the same period.

If the effectiveness gap continues to widen, it can influence the discussion about booster shots. This week, federal agencies are assessing the need for a third dose of the Pfizer-BioNTech vaccine for some high-risk groups, including the elderly.

Scientists initially skeptical of the reported differences between the Moderna and Pfizer-BioNTech vaccines have gradually become convinced that the inequality is small but real.

Natalie Dean, a biostatistician at Emory University in Atlanta, said: “It’s not a big difference, but at least it’s consistent.”

However, she and others warned that the differences are small and the actual results are uncertain, as both vaccines are still very effective in preventing serious illness and hospitalization.

John Moore, a virus expert at Weill Cornell Medicine in New York, said: “But really, how important is this difference in the real world?”

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“It is not appropriate for people who take Pfizer to be surprised to get the inferior vaccine.”

Even in the first clinical trials of the three vaccines finally approved in the United States by Pfizer-BioNTech, Moderna, Johnson & Johnson, it was clear that the J & J vaccine was less effective than the other two. Studies since then have confirmed that trend, but J & J announced this week that a second dose of the vaccine would increase its effectiveness to levels comparable to other vaccines.

The Pfizer-BioNTech and Moderna vaccines rely on the same mRNA platform, and in initial clinical trials, they had very similar efficacy against symptomatic infections. 95% for Pfizer-BioNTech and 94% for Moderna. This was part of the reason they were described as more or less equivalent.

Subtleties have emerged over time. Since vaccines have never been directly compared in carefully designed studies, the data showing different effects are primarily observational.

The results of these studies can be distorted by a variety of factors, including location, age of the vaccinated population, time of immunization, and timing between doses, Dean said.

For example, the Pfizer-BioNTech vaccine was rolled out a few weeks ago to Moderna’s priority group of seniors and healthcare professionals. Since immunity weakens faster in the elderly, the decline observed in groups consisting primarily of the elderly can give the false impression that protection from the Pfizer-BioNTech vaccine declines rapidly.

“I’m not sure there’s a real difference,” said Dr. Bill Gruber, senior vice president of Pfizer, in light of these warnings. “I don’t think there is enough data there to make that claim.”

But now, observational studies have yielded results from many places, including Qatar, the Mayo Clinic in Minnesota, several other states in the United States, and health care workers, hospitalized veterans, or the general public. increase.

The effectiveness of Moderna for severe illness in these studies ranged from 92% to 100%. Pfizer-BioNTech numbers are down 10 to 15 percentage points.

The two vaccines differ more rapidly in their effectiveness against infection. Protection from both was weakened over time, especially after the arrival of the delta variant, but Pfizer-BioNTech vaccine levels were lower. In two recent studies, the Moderna vaccine was superior in disease prevention by more than 30 percentage points.

Some studies have found that the levels of antibodies produced by the Pfizer-BioNTech vaccine are one-third to one-half that produced by the Moderna vaccine. Still, the reduction is trivial, Moore said: for comparison, there are more than 100-fold differences in antibody levels between healthy individuals.

Still, other experts said the corpus of evidence points to disparities worth investigating, at least in people who are vulnerable to the vaccine, including the elderly and people with immunodeficiency.

“In the end, I think there are subtle but real differences between Moderna and Pfizer,” said Jeffrey, an immunologist and doctor at the University of Virginia, Charlottesville, who co-authored such a study. Dr. Wilson was featured in the JAMA Network Open this month. “In high-risk populations, that may be relevant. I hope people take a closer look.”

“Pfizer is a sledgehammer,” Wilson added, “Moderna is a sledgehammer.”

Several factors may underlie the divergence. Vaccines vary depending on the dose and the time between the first and second doses.

Vaccine manufacturers usually have enough time to test different doses before choosing one. And we are doing such a test for testing the coronavirus vaccine in children.

But in the midst of last year’s pandemic, companies had to guess the optimal dose. Pfizer weighed 30 micrograms and Moderna weighed 100 micrograms.

Moderna vaccines rely on lipid nanoparticles that can deliver higher doses. And the first and second shots of the vaccine are four weeks off compared to the three Pfizer-BioNTech vaccines.

Dr. Paul Burton, Chief Medical Officer of Modana, said the extra week may give more time for immune cells to proliferate before the second dose. “We need to keep studying this and do more, but I think it’s plausible.”

The Moderna team recently showed that half the dose of the vaccine still spiked antibody levels. Based on these data, the company requested the FDA this month to approve 50 micrograms (half the dose) as booster shots.

There is limited evidence of the effect of that dose and nothing about how long the higher antibody levels will last. Federal regulators are reviewing Moderna’s data to determine if the available data is sufficient to approve half-dose booster shots.

Ultimately, both vaccines are still stable against serious illness and hospitalization, especially in people under the age of 65, Moore said.

Scientists initially wanted the vaccine to be 50% or 60% effective. “We would all have seen it as a great result and were happy with it,” he said. “We’ve been fast-forwarding to discuss whether Moderna’s 96.3% vaccine efficacy and Pfizer’s 88.8% vaccine efficacy are significant.”

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