Why COVID boosters weren't tweaked to better match variants

COVID vaccines were administered in Calhoun City, Mississippi, on Sept. 23, 2021.

COVID-19 booster shots are an extra dose of the original vaccine, and some experts wonder why they weren't updated to better match the delta variant.

Posted: Oct 18, 2021 3:28 PM

More COVID-19 booster shots may be on the way -- but when it’s your turn, you’ll get an extra dose of the original vaccine, not one updated to better match the extra-contagious delta variant.

And that has some experts wondering if the booster campaign is a bit of a missed 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 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 last week as government experts debated whether it's time for Moderna boosters. He wondered if such a switch would be particularly useful to block mild infection.

The simple answer: The FDA last month OK'd extra doses of Pfizer’s original recipe after studies showed it still works well enough against delta -- and those doses could be rolled out right away. Now the FDA is weighing evidence for boosters of the original Moderna and Johnson & Johnson vaccines.

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

But Pfizer and Moderna are hedging their bets. They’re already testing experimental doses customized to delta and another variant, learning how to rapidly tweak the formula in case a change eventually is needed -- for today’s mutants or a brand new one. The tougher question for regulators is how they’d decide if and when to ever order such a switch.

What we know so far:

CURRENT VACCINES ARE WORKING EVEN AGAINST DELTA

Vaccines used in the U.S. 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 EVEN 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 to people deemed to need them now.

Still, because delta is now the dominant version of the virus 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.

A delta-updated vaccine would “help to provide a buffer against those additional mutations,” he said. Bedford is paid by the Howard Hughes Medical Institute, which also supports The Associated Press Health and Science Department.

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 it's trained to recognize the virus. Updating the formula merely 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, the beta variant, that has been the most vaccine-resistant to date, more so than the delta variant. Lab tests showed the updated shots produced potent antibodies. But the beta 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 -- much like today’s flu vaccines work against multiple influenza strains.

The mRNA vaccines are considered the easiest kind to tweak but some other vaccine makers also are exploring how to change their recipes if necessary.

WHY STUDY UPDATED SHOTS IF THEY’RE NOT YET NEEDED?

Moderna's Dr. Jacqueline Miller told an FDA advisory panel last week the company is studying variant-specific boosters now to learn if they offer advantages, and to be ready if they're needed.

And Penn’s Wherry said it is critical to carefully 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’s made before -- or the bigger goal, a broader and more durable response that might even be better positioned for the next mutations to come along.

NO RULES YET FOR MAKING A SWITCH

“What is the tripping point?” asked Webby, who is part of a World Health Organization network that tracks influenza evolution. “A lot of what is going to need to go into that decision making is just going to be learned by experience, unfortunately.”

Bedford said now is the time to decide what drop in vaccine effectiveness would trigger a formula change, just as is done with flu vaccines every year.

That’s important not just if a dramatically worse variant suddenly develops. 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 noted.

“Your boostability may actually improve with longer intervals between stimulation,” he said. While scientists have learned a lot about the coronavirus, “the story’s not finished yet and we don’t know what the last chapters say.”

Mississippi Coronavirus Cases

Data is updated nightly.

Cases: 512632

Reported Deaths: 10262
CountyCasesDeaths
Harrison34853555
DeSoto33162432
Hinds32556641
Jackson24830389
Rankin22442402
Lee16238242
Madison14874283
Jones14086247
Forrest13741259
Lauderdale12249324
Lowndes11286193
Lamar10644140
Pearl River9707244
Lafayette8827143
Hancock7835132
Washington7550169
Oktibbeha7204138
Monroe6989179
Pontotoc6970109
Warren6849178
Panola6746134
Neshoba6726210
Marshall6653141
Bolivar6440151
Union633897
Pike5924156
Alcorn5862107
Lincoln5525136
George510180
Prentiss500884
Tippah490282
Itawamba4829107
Scott477499
Adams4766125
Tate4748116
Leflore4723144
Copiah455895
Yazoo455591
Simpson4543117
Wayne442772
Covington432895
Sunflower4299106
Marion4265112
Coahoma4227109
Leake413790
Newton395581
Tishomingo381793
Grenada3775109
Stone365666
Jasper340166
Attala337790
Winston317792
Chickasaw313367
Clay311878
Clarke301195
Calhoun284449
Holmes271289
Smith268952
Yalobusha243747
Tallahatchie231453
Greene224749
Walthall221366
Lawrence217840
Perry213356
Amite209557
Webster205148
Noxubee188642
Montgomery181557
Carroll174441
Jefferson Davis173643
Tunica163239
Benton152639
Kemper144941
Choctaw136527
Claiborne134238
Humphreys131139
Franklin124929
Quitman107528
Wilkinson105939
Jefferson96834
Sharkey65121
Issaquena1957
Unassigned00

Alabama Coronavirus Cases

Cases: 844594

Reported Deaths: 16115
CountyCasesDeaths
Jefferson1160612006
Mobile741651379
Madison53255732
Shelby38313368
Baldwin38061589
Tuscaloosa35996641
Montgomery34473781
Lee25541263
Calhoun22582518
Morgan22441406
Etowah20009517
Marshall18771316
Houston17723425
St. Clair16863358
Limestone16123218
Cullman16032303
Elmore15902294
Lauderdale14945306
Talladega14186299
DeKalb12957269
Walker12011380
Blount10700192
Autauga10512157
Jackson10151194
Coffee9412192
Colbert9325208
Dale9013191
Tallapoosa7248201
Russell707465
Chilton7015170
Escambia6951143
Covington6926195
Franklin6337108
Chambers5778142
Marion5400130
Dallas5283209
Pike5114109
Clarke484986
Lawrence4826129
Winston4777110
Geneva4640136
Bibb434094
Barbour369180
Butler3433100
Marengo342393
Monroe336666
Randolph334067
Pickens333188
Fayette329885
Henry320566
Hale317989
Cherokee316963
Crenshaw260477
Washington256952
Cleburne254360
Lamar251253
Clay250869
Macon244764
Conecuh192762
Coosa184647
Lowndes178168
Wilcox177438
Bullock152545
Perry141840
Sumter139041
Greene130245
Choctaw93228
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