Over the past 18 months, the original COVID-19 vaccines — first as a two-dose series, then as boosters — have done an outstanding job protecting us from illness, hospitalization, and death. Globally, they saved nearly 20 million lives in 2021 alone. Even today, unvaccinated Americans are twice as likely as vaccinated Americans to test positive for COVID—and six times more likely to die from the disease.
But viruses evolve and vaccines must too.
That was the overall picture from this week’s key meeting of the US Food and Drug Administration’s expert advisory panel. The question before them was simple: Before the expected winter surge, should vaccine manufacturers change their upcoming booster vaccines to target Omicron — the ultra-infectious variant that has spent the last seven months worldwide in one form or another — or should they stick with to the tried and true recipe for 2020?
The panel voted 19-2 on Tuesday in favor of Omicron’s amplifiers. The question now, however, is which version of the Omicron the next series of shots should be aimed at.
A healthcare worker administers a dose of Moderna’s COVID-19 vaccine in Norristown, Pennsylvania, in 2021 (Matt Rourke/AP)
For anyone who hasn’t been paying attention, the Omicron strain that caused the massive COVID wave last winter (BA.1) is now gone. In March it was replaced by the even more portable BA.2 … which was replaced in May by the even more portable BA.2.12.1 … which is now being replaced by the (you guessed it) even more portable BA.4 and BA.5.
Experts say BA.5 is the one to worry about: “The worst version of the virus we’ve seen,” as Dr. Eric Topol, the founder of the Scripps Research Translational Institute, recently put it. Together, the closely related BA.4 and BA.5 now account for the majority of new COVID cases in the US, according to the latest data from the Centers for Disease Control and Prevention – but BA.5 (36.6%) is spreading much more -faster than BA.4 (15.7%). By early July, it will be the dominant strain in the US
This is troubling for several reasons. For our immune system, the distance from BA.1 to the highly mutated BA.4 and BA.5 is “far greater,” Topol writes, than the distance from the original BA.1 virus to previous hit variants like Alpha and Delta — making them more difficult to recognize and respond to. According to the latest research, this could mean:
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None of this will get the US back on track. Despite increased case rates, there are now fewer U.S. COVID patients in intensive care units than in previous phases of the pandemic, and the national death rate (about 300-400 per day) is near an all-time low. Acquired immunity, multiple vaccinations and improved treatment options help – a lot.
But combined with waning vaccine protection and disappointing booster uptake among the elderly, the virus’ accelerating evolution and aggressive new trajectory—toward greater transmissibility, evasiveness, and eventually pathogenicity—could cause significant reinfections and disruptions if not addressed. examined.
It could also put vulnerable Americans at risk in the coming months.
A sign seen in March in New York City outlining the CDC’s guidelines for controlling the spread of COVID. (John Minchillo/AP)
In late April, BA.5 hit Portugal; by June, more Portuguese people were dying from COVID each day than during the country’s Omicron winter peak. Portugal certainly has a higher number of elderly people (23%) than the US (16%), but not by much. And the vaccination rate there is 87%, compared to just 67% in America. Meanwhile, Portugal’s booster rate is almost twice as high as ours. Infection and hospitalization rates are also rising in much of the rest of Europe.
At Tuesday’s FDA advisory meeting, Justin Lesler, an epidemiologist at the University of North Carolina at Chapel Hill, presented a series of predictions about how the virus could affect the United States in the coming months. The most optimistic scenario? About 95,000 new deaths between March 2022 and March 2023. The most pessimistic? More than 200,000.
So given that BA.5 – which is once again ahead of its cousin BA.4 – will soon be everywhere, it seems logical that the next version of the vaccine would be tailored to combat it.
But that’s not necessarily the plan. Both Pfizer and Moderna have already started clinical trials for redesigned fall boosters… but these boosters are optimized to counter the now-defunct BA.1, not the soon-to-be-dominant BA.5. According to data presented Tuesday by Pfizer, their existing BA.1 booster generated a significantly lower level of neutralizing antibodies against BA.4 and BA.5 than against BA.1.
Vials of Pfizer-BioNTech’s COVID-19 vaccine are set to be packaged in 2021 (Pfizer via AP)
Yet in mice, at least the booster containing BA.4 and BA.5 produced a higher neutralizing response to all Omicron variants (including BA.4 and BA.5) than the original vaccine.
Despite concerns about “scarce” data about whether bivalent boosters (equal parts original strain and Omicron) work better than monovalent boosters (100% Omicron) and whether it’s worth waiting for Novavax’s promising non-mRNA vaccine to come out market, the panel most agreed that BA.4/BA.5 boosters make sense. The FDA is also leaning toward it. Pfizer said it was “prepared” to ship the new boosters by the first week of October; Moderna, by the last week of October or early November — “assuming there are no clinical data requirements.”
This means no human trials – only animal trials and laboratory tests. That might sound scary to some, but regulators already use the same expedited process to update the flu vaccine every year — and there’s no mechanism by which minor tweaks to the mRNA would make Pfizer and Moderna’s revised shots any less safe than billions of doses. applied so far around the world. Otherwise, the US will miss its fall-winter deadline and the fast-evolving virus will continue to outpace vaccines.
The FDA itself will decide “very quickly” what to recommend; manufacturers will follow suit.
A syringe of Pfizer’s COVID-19 vaccine is being prepared in Chester, Pennsylvania, in 2021. (Matt Rourke/AP)
In the future, chasing options may not prove to be the most effective or efficient approach to vaccination against COVID. As Topol said, “by the time the BA.5 vaccine booster is potentially available, who knows what … the predominant strain will be”? That’s why it was welcome news on Wednesday when Pfizer and BioNTech announced plans to “begin human trials of next-generation injections that protect against a wide variety of coronaviruses in the second half of the year,” according to a Reuters report.
These include “T-cell-boosting shots designed primarily to protect against severe disease if the virus becomes more dangerous” and “pan-coronavirus shots that protect against the wider family of viruses and its mutations”. Nasal vaccines designed to stop infection before it starts are also showing promise.
But these are increasingly long-term propositions. At least this year, a BA.5 booster is probably our best bet to minimize infection, disease and death during another likely winter spike.
“I fully expect further evolution to occur in the coming months, but that evolution will most likely be above BA.4/BA.5 – and so [it] should not dissuade vaccine updates,” virologist Trevor Bedford of the Fred Hutchinson Cancer Research Center in Seattle wrote earlier this week. “I believe the decision-making process boils down to: vaccine formulations that can be produced in time for fall distribution that we expect to generate the highest [protection] vs. BA.4/BA.5?’
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