Over the past 18 months, the original COVID-19 vaccines — first as a two-dose series, then as boosters — have done an extraordinary job of protecting us from illness, hospitalization, and death. Worldwide, they have 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 as likely to die from the disease.
But viruses evolve, and vaccines should too.
That was the big conclusion of a pivotal meeting this week of the US Food and Drug Administration’s advisory panel of experts. The question before them was simple: Ahead of an expected winter wave, should vaccine makers adjust their upcoming booster shots to target Omicron – the ultra-infectious variant that has been spreading in some form around the world over the past seven months? has gone up – or should they stick with the tried and true 2020 recipe?
The panel voted 19-2 in favor of Omicron boosters on Tuesday. The question now is which one version of Omicron should target the next round of shots.
For anyone who hasn’t been paying attention, the Omicron species that caused last winter’s massive COVID wave (BA.1) is now extinct. In March it was supplanted by the even more transferable BA.2…which was supplanted in May by the even more transferable BA.2.12.1…which is now being replaced by the (you guessed it) even more transferable 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 Scripps Research Translational Institute, recently put it. Together, the closely related BA.4 and BA.5 now account for the majority of new US COVID cases, according to the latest data from the Centers for Disease Control and Prevention — but BA.5 (36.6%) is spreading much faster than BA.4 (15.7%). In early July it will be the dominant species in the US
That is difficult for several reasons. For our immune system, the distance from BA.1 to heavily mutated BA.4 and BA.5 is “much greater,” Topol writes, than the distance from the original BA.1 virus to previous blockbuster variants such as Alpha and Delta — making them more difficult to spot and respond to. According to the latest research, that could mean:
None of this will bring the US back to square one. Despite an increased number of cases, there are now fewer U.S. COVID patients in intensive care units than during earlier phases of the pandemic, and the national death rate (about 300-400 per day) is near an all-time low. Acquired immunity, multiple rounds of vaccinations and improved treatment options help – a lot.
But coupled with declining vaccine protection and disappointing booster uptake among the elderly, the accelerating evolution of the virus and its aggressive new trajectory – towards greater transmissibility, evasion and possibly pathogenicity – could cause significant reinfections and disruption if left unaddressed.
It could also put vulnerable Americans at risk in the coming months.
At the end of April, BA.5 hit Portugal; in June, more Portuguese were dying from COVID each day than during the Omicron winter peak in the country. Sure, Portugal has a larger senior population (23%) than the US (16%), but not by much. And the vaccination rate there is 87%, compared to only 67% in America. Portugal’s booster rate is now almost twice as high as ours. The number of infections and hospitalizations is now rising also in much of the rest of Europe.
At Tuesday’s FDA advisory meeting, Justin Lessler, an epidemiologist at the University of North Carolina at Chapel Hill, presented a series of projections about how the virus could affect the US 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 once again surpasses its cousin BA.4 – will soon be everywhere, it seems logical that the next version of the vaccine should be tailored to fight it.
Still, that hasn’t necessarily been the plan. Both Pfizer and Moderna have already launched clinical trials for redesigned trap boosters… but those boosters have been optimized to counter the now-non-existent BA.1 rather than the soon-to-be-dominant BA.5. According to data presented by Pfizer on Tuesday, their existing BA.1 booster generated significantly lower levels of neutralizing antibodies against BA.4 and BA.5 than against BA.1.
But in mice, a booster with BA.4 and BA.5 produced at least a stronger neutralizing response to all Omicron variants (including BA.4 and BA.5) than the original vaccine.
Despite concerns about “little” data on whether bivalent boosters (equal parts parent strain and Omicron) work better than monovalent boosters (100% Omicron), and whether it is worth waiting for the promising non-mRNA vaccine from Novavax comes to market, the panel largely agreed that BA.4/BA.5 boosters make sense. The FDA is also leaning in that direction. Pfizer said it was “prepared” to deliver the new boosters in the first week of October; Moderna, by the last week of October or early November — “assuming no clinical data requirements.”
That means no human testing – just animal and laboratory testing. That may 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 mRNA tweaks will make revised Pfizer and Moderna shots less safe than the billions of doses that are so are administered. far worldwide. Otherwise, the US will miss the fall-winter deadline and the rapidly evolving virus will continue to elude vaccines.
The FDA itself will decide “very quickly” what to recommend; manufacturers will follow suit.
Going forward, chasing variants may not prove to be the most effective or efficient approach to COVID vaccination. As Topol put it, “by the time a BA.5 vaccine booster may be available, who knows what…will be the predominant strain”? That’s why it was welcome news Wednesday when Pfizer and BioNTech announced they plan to “start human testing of next-generation injections that protect against a wide variety of coronaviruses in the second half of the year,” according to a report. from Reuters.
These include “T-cell boosting injections, designed to protect against serious illness in the first place if the virus becomes more dangerous,” and “pan-coronavirus shots that protect against the wider family of viruses and its mutations.” Nasal vaccines that aim to stop infection before it starts also show promise.
But these are all proposals for the longer term. This year, a BA.5 booster is probably our best bet for minimizing infection, illness, and death during another likely winter surge.
“I fully expect that there will be further evolution in the coming months, but that this evolution will most likely be on top of BA.4/BA.5 — and thus [it] should not discourage vaccine updates,” virologist Trevor Bedford of the Fred Hutchinson Cancer Research Center in Seattle wrote earlier this week. “I believe the decision-making process comes down to: From vaccine formulations that can be manufactured in time for distribution in the fall, which we expect to have the highest [protection] against BA.4/BA.5?”
