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Another way to think about the best COVID vaccine

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Back in February, when COVID-19 vaccines were still largely restricted to the most vulnerable among us, public health leaders were determined to send a unified message: don’t worry about the differences between vaccines. “All three are really pretty good, and people should go with the one that is best available to them,” Anthony Fauci called At Meet the press.

Now that hundreds of millions of vaccine doses have been distributed in the United States, we have many reasons to doubt this story. A recent (but not yet peer-reviewed) study of more than half a million U.S. veterans showed that the Johnson & Johnson syringe had protection against infection (whether or not it leads to illness or hospitalization) crashed from 88 percent to 3 percent by mid-August, while the effectiveness of the other vaccines had decreased significantly less. Research published in the last few months also shows that Moderna’s shot outperforms Pfizer’s on both counts Antibody number and Hospital stays while a National Institutes of Health study published earlier this month found that Moderna’s booster shot raised participants’ antibody levels slightly more than Pfizer’s, and that both mRNA boosters were miles ahead of the J&Js.

Given all of this data, it’s tempting to group the vaccines by brand name: Moderna is better than Pfizer is better than J&J. But the same numbers suggest a different pattern: perhaps what matters most is what vaccine you get, but how much of it.

Consider how the vaccines differ in their dosage. J&J, the least effective in the studies, has only one take on its main series; the mRNA vaccines have two. So everyone who has received J&J (and has not yet received a booster) received half as many doses in total. If you compare Pfizer to Moderna, you’ll see another dose difference: each shot of Pfizer contains 30 micrograms of mRNA, while each of Moderna contains 100. (Doses for children can also vary in size: Pfizer has suggested 10 microgram shots while Moderna is Go At 50.) How much of the difference in vaccination performance can be explained by saying, “The more vaccine is better ” sum up?

“More vaccine” is not a simple suggestion. On the one hand, Pfizer and Moderna measure doses in terms of mass of mRNA lipid nanoparticles; J&J doses are measured by counting the number of harmless adenovirus particles that each contains (approximately 50 billion). You can’t really compare lipid nanoparticles to viral particles, several experts told me. According to Michael Arand of the Institute of Pharmacology and Toxicology at the University of Zurich, one shouldn’t even assume that every 50 billion particle dose of J&J equals the next, since depending on the manufacturing details, some particles can be more contagious than others. A better dose measure for adenovirus-based vaccines, he argued in a recently published Opinion paper, would be “infectious units”. When I emailed him if it was possible to develop a standard measure that would work on different vaccine platforms, he said, “I don’t think so.”

Comparing the doses of the Pfizer and Moderna vaccines is much easier because their mechanisms are so similar. Each shot of Moderna delivers more than three times the active ingredient compared to Pfizer and appears to induce higher antibody counts and result in more permanent protection against infection and hospitalization. “Over time, that higher dose could make all the difference in protection,” said John Moore, professor of microbiology and immunology at Weill Cornell Medicine.

The vaccines also differ in their dosing schedules. Vaccinated (and unvaccinated) Americans received 60 micrograms of Pfizer over three weeks, 200 micrograms of Moderna over four weeks, or 50 billion J&J particles in one session. It’s apples and oranges, except you have to gobble the apple all at once and some of the oranges are tangerines and you can only eat a few slices at a time.

Even the week-long difference between Pfizer’s schedule and Moderna could be important. Mark Slifka, an immunologist at Oregon Health and Science University, told me it might add to Moderna’s slightly longer-lasting protection. Angela Rasmussen, a virologist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization, pointed out that the AstraZeneca vaccine – an adenovirus vector design like J & J’s – also appears to offer more protection when its doses are further apart .

The number of vaccine doses you receive also matters, regardless of your specific size and schedule. Slifka believes that the number of vaccinations is much more important than the amount that is given in each syringe. Getting more than one dose “actually makes the big difference among vaccinations,” he said, because it teaches the immune system to take a particular threat seriously. Several rounds of a moderately large dose may also be better than taking a megadose, because the more vaccine you receive at once, the worse your side effects are likely to be. “With mRNA vaccines and adenovirus vectors, there is an upper limit to how much you can give [in one dose] it’s just not a good idea beforehand, ”said Slifka.

American health officials haven’t said it yet, but J&J “really is a two-dose vaccine,” Rasmussen told me. Paul Offit, who directs the Vaccine Education Center at Children’s Hospital of Philadelphia, said J&J could turn out to be “as good as the mRNA vaccines” if you compare two doses with two doses. He also suggested that a single dose of J&J would prevent more hospitalizations and deaths than a single dose of Pfizer or Moderna.

But this opinion is anything but universal. “I have absolutely no doubt that adenoviruses are inferior to mRNAs,” said Moore. Many fans of J & J’s shot speculate that its protection from hospitalization and death could take longer than the other vaccines thanks to the way it was shot tickles a special one A set of actors in the immune system called T cells that prevent infections from turning into serious illness. “There’s kind of a T-cell mafia,” Moore said, but some studies have shown the mRNA vaccines Produce T cell responses with at least as much panache as J & J’s. He says antibodies are a better proxy for protection anyway, and the Moderna and Pfizer options consistently produce more of them in the vaccinated.

Some experts continue to suggest that all three vaccines are somewhat interchangeable. Slifka, for example, thinks so the differences between the adenovirus and mRNA formulas– the way they target our cells, the type of immune response they trigger in us – may not be particularly relevant to the protection they provide. “Both are nanoparticles. One is a virus nanoparticle and the other is a lipid nanoparticle, but both do the same, ”he said: It delivers genetic material into human cells so that these cells produce the characteristic spike protein of the coronavirus and target the immune system can give practice when the real intruder arrives.

We’ll probably never be sure how much of the difference between the vaccines is due to their formulas and how much is from other factors. In theory, researchers could unravel these questions by running huge randomized controlled trials with slightly larger and smaller doses of each shot, and with varying intervals between (equally sized) shots. But with half the world still not receiving a single dose of a COVID-19 vaccine, and with many good enough regimens already identified, no one is going to devote resources to such fine-grained questions.

“If last year hadn’t been such a shit storm,” said Moore, “all these problems would have been ironed out.” Right now, we have to stumble further with our clunky toolbox of boosters, wait times, and half doses – counting our blessings to live in a country where we have the luxury of wondering how much vaccine is the best amount.


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