More covid-19 booster shots may be on the way -- but recipients will be getting 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.
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"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 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 order such a switch.
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.
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.
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.
NORTHERN SPREAD
Changes are also being seen in the patterns of spread by the coronavirus as many counties across the country's northernmost regions are experiencing rising cases as colder weather arrives, even as the virus recedes in much of the rest of the United States.
The top five states in new daily cases per capita are led by Alaska, which is logging the highest daily average: 125 cases per 100,000 people, according to a New York Times database. The next four states, with at least 67 cases per 100,000 people, are Montana, Wyoming, North Dakota and Idaho.
Cases are at least trending downward or holding steady in those states. The five states with the fastest-rising caseloads are Vermont, Colorado, New Hampshire, Michigan and Minnesota, and the two counties with the most cases per capita in Vermont and New Hampshire are on the Canadian border.
The virus followed a similar pattern last fall: Cases receded in the Southern regions after summer surges, while they steadily increased throughout the North as the weather became colder and people moved indoors.
The big difference this year is that covid-19 vaccines are widely available, and most experts don't expect another catastrophic winter wave, but they are warning Americans not to let their guard down as long as a large portion of the population remains unvaccinated.
"The weather drives people indoors into poorly ventilated spaces, and when either academic activities or social activities occur without masks in indoor, poorly ventilated spaces, that's when transmission occurs," said Dr. Natasha Bagdasarian, Michigan's chief medical executive, adding that winter was "coming at a very bad time for us here in Michigan."
AROUND THE WORLD
In Australia, Sydney has further eased restrictions after the state of New South Wales passed its target of fully vaccinating 80% of the eligible population.
On Monday, thousands of children returned to school after months of home learning and a lockdown that lasted more than 100 days. Up to 20 fully vaccinated people can gather in a private home, and there is no limit on the number of fully vaccinated people who can attend a funeral or wedding.
"Today's our first day of post-80% life," Dom Perrottet, the premier of New South Wales, posted to Twitter. He added: "Do the right thing."
The easing comes as Australia has moved away from trying to eradicate covid-19, instead aiming to vaccinate as much of its population as possible.
The goal is to begin to reopen fully once 80% of the national population is vaccinated. As of Monday, 56% of the country's population was fully vaccinated, and 72% had one dose, according to data from The New York Times.
As part of that strategy, the city of Melbourne -- which has endured among the most days in lockdown of any in the world -- will lift its stay-at-home orders at 11:59 p.m. Thursday, when 70% of eligible adults are expected to be fully vaccinated.
Encouraging trends were also seen Monday in Mexico, where the capital city returned to the lowest level on the nation's covid-19 pandemic warning system for the first time since June.
In practice, the shift from the yellow to green category meant only small changes to daily life. Mask wearing is still common in streets of the city of 9 million, but the rhythm of life in the capital has long since regained a high degree of normalcy.
Large outdoor events, which had been operating at 75% capacity, now face no capacity restrictions, though attendees will still be required to wear masks. The move comes just weeks ahead of Mexico City hosting a Formula 1 race.
Bars, clubs and event halls are allowed an additional hour of operation and will now stay open until 1 a.m., though with the same health filters required at their entrances checking temperatures and providing disinfectant gel.
The number of people in the metropolitan area hospitalized with covid-19 or suspected cases has been falling since mid-August.
In Italy on Monday, the president strongly criticized the violence that has broken out amid protests over the country's new coronavirus workplace health pass requirement, saying it appeared aimed at jeopardizing Italy's economic recovery.
President Sergio Mattarella spoke out as riot police again clashed with protesters at the port in the northern city of Trieste, at times using water cannons to push them back. The protesters, who have included right-wing agitators in previous episodes, oppose Italy's Green Pass requirement.
Italy on Friday became the first major European economy to require all workers -- from hairdressers to factory workers -- to present proof of vaccination, a negative test within the past 48 hours or proof of having been cured recently to enter workplaces. The pass had already been required to enter indoor venues like restaurants, museums and theaters, or for long-distance domestic travel.
The government says the measure is necessary to ensure workplaces are safe so that Italy's economy, which shrank 8.9% last year, can recover. Opponents say the requirement violates their rights and imposes unfair burdens on workers and employers alike.
The aim of the Green Pass requirement is to encourage even higher vaccination rates beyond the current 81% of Italy's population older than 12 who are fully inoculated.
Information for this article was contributed by Lauran Neergaard and Nicole Winfield of The Associated Press; and by Daniel E. Slotnik and Livia Albeck-Ripka of The New York Times.