Why COVID Boosters Have Not Been Adapted To Better Fit Options

More COVID-19 booster vaccines may be available soon, but when it is your turn, you will receive an additional dose of the original vaccine, not the one that was updated to better match the extra-infectious delta option.

And it makes some experts question whether the booster campaign is a slightly missed opportunity to target Delta and its likely descendants.

“Don’t we want to match new strains that are most likely to circulate as close as possible?” Dr. Cody Meisner of Tufts Medical Center, FDA advisor, recently challenged Pfizer scientists.

“I don’t quite understand why this is not a delta, because this is what we are facing right now,” fellow consultant Dr. Patrick Moore of the University of Pittsburgh said last week when government experts discussed whether it was time for the Moderna boosters. … He wondered if such a switch would be particularly useful for blocking out a mild infection.

Simple answer: The FDA approved additional doses of the original Pfizer prescription last month after studies showed it still worked reasonably well against delta – those doses could be applied right away. The FDA is now reviewing evidence of original Moderna and Johnson & Johnson vaccine boosters.

“This is less churn and burns in production” so that you only change formulas when you really need to, “said FDA vaccine chief Dr. Peter Marks.

But Pfizer and Moderna are hedging their bets. They are already testing experimental doses, adapted to delta and another variant, learning to quickly tune the formula in case a change eventually needs to be made – for today’s mutants or completely new ones. A more difficult question for regulators is how they will decide whether and when to order such a switch.

What we know at the moment:

Modern vaccines even work against delta

Vaccines used in the US remain highly effective against hospitalization and death from COVID-19 even after the delta variant took over, but authorities hope to bolster weakened protection against less severe infections and for high-risk groups. Research shows that an extra dose of the original formulas boosts antiviral antibodies that ward off infection, including antibodies that target delta.

Could a delta-specific booster perform even better?

The vaccines target the spike protein that covers the coronavirus. Mutations in this protein made the delta more infectious, but that’s not all that different for the immune system, said viral expert Richard Webby of St. Jude Children’s Research Hospital.

This means there is no guarantee that a delta-specific booster will defend better, said University of Pennsylvania immunologist John Werry. Waiting for research to address this – and, if necessary, creating updated doses – would postpone the release of boosters for people believed to need them now.

However, since delta is now the dominant version of the virus globally, it will almost certainly become a common ancestor for everything that will evolve in the largely unvaccinated world, said Trevor Bedford, a biologist and genetics expert at Fred’s Cancer Research Center. Hutchinson.

The delta-update vaccine “will help buffer these additional mutations,” he said. Bedford receives money from the Howard Hughes Medical Institute, which also supports the Associated Press’s Department of Health and Science.

Setting up a recipe

The Pfizer and Moderna vaccines are made using a piece of genetic code called an RNA messenger that tells the body to create harmless copies of the spike protein so it can be trained to recognize the virus. Updating the formula simply requires replacing the original genetic code with mRNA for the mutant spike protein.

Both companies first experimented with modified doses against a mutant originating in South Africa, the beta variant, which is by far the most resistant to vaccines, rather than the delta variant. Laboratory tests have shown that the renewed injections produce potent antibodies. But the beta version was not widely adopted.

Companies are now conducting studies on fully vaccinated people who have agreed to test a delta-adjusted booster dose. Moderna’s research also includes multiple vaccines that combine protection against more than one version of the coronavirus – in the same way that modern influenza vaccines work against multiple strains of influenza.

It is believed that mRNA vaccines are the easiest to customize, but several other vaccine manufacturers are also looking into how to change their recipes if necessary.

Why study updated snapshots if you don’t need them yet?

Moderna’s Dr. Jacqueline Miller told an FDA advisory panel last week that the company is currently studying boosters for specific options to see if they offer benefits and to be ready if needed.

And Werry of Penn said it is very important to carefully analyze how the body responds to renewed injections because the immune system tends to “imprint” a stronger memory of the first strain of the virus it encounters. This raises questions about whether a slightly different booster will cause a temporary jump in antibodies that the body has made before, or a larger target, a broader and more robust response that may be even better prepared for the next mutations.

There are no rules to switch yet

“What is a trigger point?” asked Webby, who is part of the World Health Organization’s influenza network. “A lot of what will be required to make this decision, unfortunately, will simply be learned from our own experience.”

Bedford said now is the time to decide how much of a decrease in vaccine efficacy will cause a formula change, as happens with flu vaccines every year.

This is important not only if the worst case suddenly develops. Like many scientists, Bedford expects the coronavirus will eventually turn from a global crisis to a regular threat every winter, which could mean more regular boosters, perhaps even annually in combination with a flu shot.

Werry noted that the time between shots also matters.

“Your enhancement ability can really improve with longer stimulation intervals,” he said. Although scientists have learned a lot about the coronavirus, “the story is not over yet and we don’t know what the final chapters are saying.”

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