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A version of this article first appeared in Katelyn Jetelina’s newsletter, Your local epidemiologist.
Last week, the Food and Drug Administration’s external review committee voted against a third dose of Pfizer for the general public. They recommended a third injection for the elderly and some other higher risk groups. But the question of who needs reminders and when is still open.
As we examine the possibility of a third dose of mRNA, another important question has surfaced: does Pfizer and Do the people at Moderna need a third dose? Or just the folks at Pfizer? In other words, is there a significant difference between protecting Moderna and Pfizer from COVID-19?
Throughout the pandemic, I have always brought Moderna and Pfizer together. For example, if there was evidence that Pfizer worked against a variant, then Moderna surely worked too. These mRNA vaccines are incredibly similar, but they are not the same. There are some subtle differences between the two. First, the formulation: the fat bubbles that carry mRNA are a little different in their chemical structure. The dose of RNA encapsulated in these fat bubbles is also different: Moderna has a much higher dose (100 micrograms) compared to Pfizer (30 micrograms). The vaccines are also given on a different schedule, with doses of Moderna four weeks apart and Pfizer three. And finally, a difference in the situation that still affects the data we make decisions with: Pfizer was approved in the United States (and around the world) a few weeks (or in some cases months) before Moderna.
At first, these small differences did not affect the effectiveness of the vaccine. Both vaccines were extremely effective in protecting against asymptomatic, mild, moderate and severe illnesses. But history may be changing.
Last month, the Mayo Clinic published a prepublication of a very large study involving 645,109 patients who were followed up after vaccination (January-July 2021). The scientists wanted to describe the breakthrough rates among people vaccinated with Moderna and with Pfizer, compared to the rates of COVID-19 among unvaccinated people. How did the vaccines hold up?
They found that both vaccines continued to work very well against hospitalization, ICU admission, and death (there were no deaths in the study). This was the case in January 2021 and it was the case in July 2021. That has not changed.
Efficacy against any infection (hence, mild to moderate disease), however, was lower for both vaccines in July (76 percent effectiveness) compared to January (86 percent effectiveness). Interestingly, Pfizer’s efficacy decreased more rapidly over time (i.e. more breakthrough cases) compared to patients vaccinated with the Moderna vaccine (i.e. less revolutionary cases). Nevertheless, both vaccines were much better at preventing infections compared to no vaccine (unvaccinated patients).
We also saw this in another study, which tested 196 residents of nursing homes for the elderly in Canada after vaccination. Interestingly, residents with Pfizer rose 3.89 times less neutralizing the antibodies that residents with Moderna. This was most evident with the beta variant (first discovered in South Africa, also known as B.1.351).
On August 30, a Belgian study was published in JAMA. Scientists examined the levels of antibodies against the spike protein in 1,647 workers at a hospital in Belgium. Levels among those who received two doses of Moderna vaccine averaged 2,881 units per milliliter, compared to 1,108 units per milliliter among those who received two doses of Pfizer. The immune response was even more important for vaccinated people who had been previously infected. So the number of antibodies was higher, but as you may know, these numbers are not really significant. We don’t know what antibody number you need to say “you are protected”.
A study from Qatar largely found the same.
And, finally, the most recent study was published Friday by the Centers for Disease Control and Prevention. The CDC published a study that assessed the effectiveness of three vaccines: Moderna, Pfizer, and Johnson & Johnson. They analyzed data from 3,689 adults hospitalized in 21 hospitals in 18 states between March and August 2021. Immunocompromised patients were excluded. What did they find? The effectiveness of Moderna against hospitalization was 93%. Pfizer’s effectiveness was significantly lower at 88 percent. The effectiveness of Pfizer against hospitalization has also been descending over time, while Moderna’s effectiveness has remained stable.
So is there really a difference? May be. But we don’t know Why Again. This could be due to the higher dosage of RNA in Moderna compared to Pfizer. The higher dosage may possibly explain the longevity of the response (or the strength against delta). This could be the four weeks between doses at Moderna versus the three weeks at Pfizer – the more time between doses, the stronger the response. We have seen this time and time again (and it may explain why we need a third dose). Maybe now is the time. Moderna was proposed later than Pfizer. This time difference, at the population level, can influence this difference. In other words, Moderna can also start to shrink; it just hasn’t had the time yet like Pfizer has.
Or it could be nothing. The aforementioned studies had limitations (like all studies), which may bias the conclusions. We need more studies showing the same among different populations to be more confident. We also need to understand why. What makes the difference and why does the efficiency seem to be degrading?
Both vaccines continue to work against hospitalization and death. Will Moderna’s efficiency end up declining like Pfizer’s? Will Pfizer’s effectiveness against serious illnesses continue to decline in the general population as we have seen in Israel? This, ladies and gentlemen, is at the origin of the heated scientific debate among scientists. We can’t stop all breakthrough infections, so is there a need for a general public recall? And if so, when?
Future Tense is a partnership between Slate, New America, and Arizona State University that examines emerging technologies, public policy, and society.
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