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Why COVID boosters weren’t tweaked to better match variants

Pfizer and Moderna already are testing experimental doses customized to fight the Delta variant and another mutation of the virus. Here’s why they and the FDA didn’t wait.

Vials of the Moderna and Pfizer COVID-19 vaccines. The federal Food and Drug Administration approved extra doses of Pfizer’s original COVID-19 vaccine after studies showed it still works well enough against the Delta variant. And the FDA is weighing evidence for boosters of the original Moderna and Johnson & Johnson vaccines.
Vials of the Moderna and Pfizer COVID-19 vaccines. The federal Food and Drug Administration approved extra doses of Pfizer’s original COVID-19 vaccine after studies showed it still works well enough against the Delta variant. And the FDA is weighing evidence for boosters of the original Moderna and Johnson & Johnson vaccines.
Charles Krupa / AP

When it’s your turn for COVID-19 booster shots, you’ll get an extra dose of the original vaccine, not one updated to better match the extra-contagious Delta variant.

That has some experts wondering whether the booster campaign missed an opportunity to target Delta and its likely descendants.

“Don’t we want to match the new strains that are most likely to circulate as closely as possible?” Dr. Cody Meissner of Tufts Medical Center, an adviser to the federal Food and Drug Administration, challenged Pfizer scientists recently.

“I don’t quite understand why this is not Delta because that’s what we’re facing right now,” fellow adviser Dr. Patrick Moore of the University of Pittsburgh said.

He wondered whether such a switch might be particularly useful to block mild infection.

The FDA approved giving extra doses of Pfizer’s original recipe — the first boosters approved — after studies showed it still works well enough against Delta. Another factor: Those doses could be rolled out right away.

“It’s less churn and burn on the manufacturing” to switch formulas only when it’s really necessary, said FDA vaccine chief Dr. Peter Marks.

But Pfizer and Moderna already are testing experimental doses customized to Delta and another variant.

Here’s what we know so far:

CURRENT VACCINES ARE WORKING EVEN AGAINST DELTA

Vaccines used in the United States remain strongly effective against hospitalization and death from COVID-19 even after the Delta variant took over.

But authorities hope to shore up waning protection against less-severe infection and for high-risk populations. Studies show an extra dose of the original formulas revs up virus-fighting antibodies that fend off infection, including antibodies that target Delta.

MIGHT A DELTA-SPECIFIC BOOSTER WORK BETTER?

Vaccines target the spike protein that coats the coronavirus. Mutations in that protein made Delta more contagious.

But, to the immune system, it doesn’t look all that different, said virus expert Richard Webby of St. Jude Children’s Research Hospital.

That means there’s no guarantee a Delta-specific booster would protect any better, said University of Pennsylvania immunologist John Wherry.

Waiting for studies to settle that question — and, if necessary, brewing updated doses — would have delayed rolling out boosters.

Still, because Delta is now the dominant variant worldwide, it almost certainly will be a common ancestor for whatever evolves next in a mostly unvaccinated world, said Trevor Bedford, a biologist and genetics expert at the Fred Hutchinson Cancer Research Center in Seattle.

A Delta-updated vaccine would “help to provide a buffer against those additional mutations,” Bedford said.

TWEAKING THE RECIPE

The Pfizer and Moderna vaccines are made with a piece of genetic code called messenger RNA that tells the body to make harmless copies of the spike protein so the body’s defenses are trained to recognize the virus. Updating the formula just requires swapping out the original genetic code with mRNA for a mutated spike protein.

Both companies first experimented with tweaked doses against a mutant that emerged in South Africa that’s been the most vaccine-resistant to date, more than the Delta variant. Lab tests showed the updated shots produced potent antibodies. But the South Africa variant didn’t spread widely.

Now, the companies have studies underway of fully vaccinated people who agreed to test a booster dose tweaked to match Delta. Moderna’s studies also include some shots that combine protection against more than one version of the coronavirus — like today’s flu vaccines work against multiple influenza strains.

WHY STUDY UPDATED SHOTS?

Moderna’s Dr. Jacqueline Miller told an FDA advisory panel the company is studying variant-specific boosters now to see whether they offer advantages.

Penn’s Wherry said it’s critical to analyze how the body reacts to updated shots because the immune system tends to “imprint” a stronger memory of the first virus strain it encounters.

That raises questions about whether a subtly different booster would prompt a temporary jump in antibodies the body made before — or, better, a broader and more durable response that might even be better positioned for future mutations.

NO RULES YET FOR MAKING A SWITCH

Bedford said now is the time to decide how much of a drop in vaccine effectiveness would trigger a formula change, much like what’s done with flu vaccines every year.

Like many scientists, Bedford expects the coronavirus to eventually evolve from a global crisis into a regular threat every winter — which might mean more regular boosters, maybe even yearly in combination with the flu shot.

Timing between shots matters, too, Wherry said.

“Your boostability may actually improve with longer intervals between stimulation,” he said.