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 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 should too.
That was the broad conclusion of a pivotal meeting this week of the U.S. Food and Drug Administration’s expert advisory panel. The question before them was simple: Ahead of an expected winter surge, vaccine makers should tweak their next booster shots to target Omicron, the ultra-infectious variant that has spent the last seven months on the rise around the world in one form or another, or should they stick with the tried-and-true recipe of 2020?
The panel voted 19-2 Tuesday in favor of the Omicron reinforcements. The question now, however, is which version from Omicron the next round of shots should aim.
For anyone who hasn’t been paying attention, the Omicron strain that triggered last winter’s massive wave of COVID (BA.1) is now extinct. In March, it was supplanted by the even more transmissible BA.2… which was supplanted in May by the even more transmissible BA.2.12.1… which is now being supplanted by (you guessed it) even more transmissible BA.4 and BA.5.
Experts say BA.5 is something to worry about: “The worst version of the virus we’ve ever seen,” as Dr. Eric Topol, the founder of the Scripps Translational Research Institute, I put it recently. Together, the closely related BA.4s and BA.5s now account for the majority of new COVID cases in the US, according to the most recent data from the Centers for Disease Control and Prevention — but BA.5 (36.6%) is spreading much faster than BA.4 (15.7%). By early July, it will be the dominant strain in the US.
That is problematic for several reasons. For our immune system, the distance between BA.1 and heavily mutated BA.4 and BA.5 is “much older”, writes Topol, that the distance from the original BA.1 viruses to earlier successful variants like Alpha and Delta, making them more difficult to recognize and respond to. According to the latest research, that could mean:
None of this will bring America back to square one. Despite elevated case levels, there are now fewer COVID patients in the US in intensive care units than during earlier phases of the pandemic, and the national death rate (about 300-400 per day) is rising. near the historic low. Acquired immunity, multiple rounds of vaccination, and better treatment options are helping a lot.
But combined with decreased protection from vaccines and disappointing booster intake among the elderlythe accelerated evolution of the virus and its aggressive new trajectory (towards increased transmissibility, evasiveness, and possibly pathogenicity) could cause reinfections and significant disruptions if not addressed.
It could also endanger vulnerable Americans for months to come.
At the end of April, BA.5 arrived in Portugal; by June, more Portuguese died of COVID every day than during the country’s winter Omicron peak. Portugal certainly has a larger population of older adults (23%) than the US (16%), but not by much. And the vaccination rate there is 87%, compared to only 67% in the United States. Portugal’s reinforcement rate, meanwhile, is almost twice as tall like ours Infection and hospitalization rates are now rising in much of the rest of Europe as well.
At Tuesday’s FDA advisory meeting, Justin Lessler, an epidemiologist at the University of North Carolina at Chapel Hill, presented a series of projections for how the virus could affect the US in the coming months. The most optimistic scenario? Some 95,000 new deaths between March 2022 and March 2023. The most pessimistic? More than 200,000.
So given that BA.5, which is, again, outperforming its cousin BA.4, will soon be everywhere, it seems only fitting that the next version of the vaccine be tailored to combat it.
However, that has not necessarily been the plan. Both Pfizer and Moderna have already launched clinical trials for the redesigned drop boosters… but those boosters are optimized to counter the now-defunct BA.1 instead of the soon-to-be-dominant BA.5. According to data presented Tuesday by Pfizer, its existing BA.1 booster generated a significantly lower level of neutralizing antibodies against BA.4 and BA.5 than against BA.1.
However, in mice, at least one booster containing BA.4 and BA.5 produced a greater neutralizing response to all Omicron variants (including BA.4 and BA.5) than the original vaccine.
Despite concerns about “sparse” data on whether bivalent boosters (equal parts parent strain and Omicron) work better than monovalent boosters (100% Omicron), and whether it’s worth waiting for the promising vaccine Without Novavax mRNA coming to market, the panel mostly agreed that the BA.4/BA.5 amplifiers make sense. The FDA is also leaning that way. Pfizer said it was “prepared” to deliver 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.”
That means no human trials, just animal trials and lab tests. 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 would make Pfizer’s and Moderna’s revised shots any less safer than the billions of doses administered so far around the world. Otherwise, the US will miss its fall-winter deadline and the rapidly evolving virus will continue to outpace vaccines.
The FDA itself will decide “very quickly” what to recommend; manufacturers will follow suit.
Going forward, chasing variants may not be the most effective or efficient approach to COVID vaccination. As Topol put it, “By the time a BA.5 vaccine booster is potentially available, who knows what will be…the predominant strain”? That’s why it was welcome news on Wednesday when Pfizer and BioNTech announced they plan to “begin human trials of next-generation vaccines that protect against a wide variety of coronaviruses in the second half of the year.” according to a Reuters report.
These include “T cell-enhancing vaccines, designed to primarily protect against severe disease if the virus becomes more dangerous” and “pan-coronavirus vaccines that protect against the broader family of viruses and their mutations.” Nasal vaccines aimed at stopping the infection before it starts also show promise.
But those are all longer-term propositions. This year at least one BA.5 booster is probably our best bet for minimizing infection, illness, and death during another likely winter surge.
“I expect further development in the coming months, but that this development will probably be above BA.4/BA.5, and so on. [it] shouldn’t deter vaccine updates,” virologist Trevor Bedford of the Fred Hutchinson Cancer Research Center in Seattle. wrote earlier this week. “I think the decision-making process can be summed up as: vaccine compositions that can be manufactured in time for distribution in the fall, that we hope will generate the most [protection] against BA.4/BA.5?”