For the past 18 months, the original COVID-19 vaccines, first as a two-dose series, then as a booster, have done an extraordinary job protecting us from disease, hospitalization, and death. Globally, in 2021 alone they saved nearly 20 million lives. 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 are evolving and so should vaccines.
This was the general idea of a key meeting this week of the US Food and Drug Administration’s expert advisory group. The question posed to them was simple: before an expected increase in winter, vaccine manufacturers would have to adjust their next booster injections to target Omicron, the ultra-infectious variant that has passed the last seven months rising around the world in one way or another, or should they stay with the proven and true 2020 recipe?
The panel voted 19-2 Tuesday in favor of Omicron boosters. The question now, though, is which version of Omicron should aim for the next round of shooting.
A health worker administers a dose of a Modern COVID-19 vaccine in Norristown, Pennsylvania, in 2021. (Matt Rourke / AP)
For anyone who hasn’t paid attention, the Omicron strain that triggered last winter’s big COVID wave (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 the BA.4 (you guessed it) even more transmissible 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, founder of the Scripps Research Translational Institute, recently said. Taken together, BA.4 and BA.5, which are closely related, now account for the majority of new cases of COVID in the US, 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 strain in the US
This is problematic for several reasons. For our immune system, the distance from BA.1 to highly mutated BA.4 and BA.5 is “much greater,” writes Topol, than the distance from the original BA.1 virus to previous highly successful variants such as Alpha and Delta. which makes them more difficult to recognize and respond to. According to the latest research, this could mean:
The story goes on
None of this will get the United States back to square one. Despite high levels of cases, there are now fewer COVID patients in the United States in intensive care units than during the earlier stages of the pandemic, and the national mortality rate (about 300-400 per day) is close to historical minimum. Acquired immunity, multiple rounds of vaccination, and improved treatment options are helping, a lot.
But, combined with declining vaccine protection and disappointing absorption of reinforcement among the elderly, the accelerated evolution of the virus, and the new aggressive trajectory, toward increased transmissibility, evasion, and possibly pathogenicity, could cause reinfections and significant interruptions if not addressed.
It could also endanger vulnerable Americans in the coming months.
A poster seen in March in New York City outlines the CDC’s guidelines for controlling the spread of COVID. (John Minchillo / AP)
In late April, BA.5 hit Portugal; in June, more Portuguese died of COVID than during the country’s winter Omicron peak. Portugal probably has a larger senior population (23%) than the US (16%), but not much. And the vaccination rate there is 87%, compared to only 67% in America. Meanwhile, Portugal’s reinforcement rate is almost double that of ours. Infection and hospitalization rates are also rising 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 on how the virus could affect the U.S. 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 again surpassing its cousin BA.4, will soon be everywhere, it seems logical that the next version of the vaccine should be adapted to combat it.
However, this has not necessarily been the plan. Both Pfizer and Moderna have already launched clinical trials for redesigned fall boosters … but these boosters are optimized to counteract the now non-existent BA.1 instead of the soon-to-be-dominant BA.5. According to data presented by Pfizer on Tuesday, its existing BA.1 reinforcement generated a significantly lower level of neutralizing antibodies against BA.4 and BA.5 than against BA.1.
The vials of the Pfizer-BioNTech vaccine against COVID-19 are being prepared for packaging in 2021. (Pfizer via AP)
However, in mice at least one 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 on whether bivalent enhancers (equal parts of original strain and Omicron) work better than monovalent enhancers (100% Omicron) and whether it is worth waiting for the promising Novavax mRNA vaccine to arrive in the market, the panel mostly agreed that reinforcements BA.4 / BA.5 make sense. The FDA is also leaning that way. Pfizer said it was “ready” to deliver the new reinforcements in the first week of October; Modern, the last week of October or early November, “assuming there are no clinical data requirements.”
This means that there are no human tests, only animal tests and laboratory tests. This may sound daunting to some, but regulators already use the same accelerated process to update the flu vaccine every year, and there is no mechanism by which minor mRNA adjustments cause revised injections of Pfizer and Modern are less safe than the billions of doses administered. far away all over the world. Otherwise, the United States will lose its fall-winter deadline and the rapidly evolving virus will continue to outnumber vaccines.
The FDA itself will decide “very quickly” what to recommend; manufacturers will follow suit.
A syringe is being prepared with the Pfizer COVID-19 vaccine in Chester, Pennsylvania, in 2021. (Matt Rourke / AP)
In the future, pursuing variants may not be the most effective or efficient approach to COVID vaccination. As Topol said, “by the time a BA.5 vaccine booster is available, who knows what the predominant strain will be”? That’s why it was welcome news Wednesday when Pfizer and BioNTech announced they plan to “start testing on humans for next-generation traits that protect against a wide variety of coronaviruses during the second half of the year,” according to a report by Reuters.
These include “cows that enhance T cells, designed primarily to protect against serious disease if the virus becomes more dangerous” and “pan-coronavirus cows that protect against the broader family of viruses and their mutations.” Nasal vaccines designed to stop the infection before it starts are also promising.
But they are all long-term proposals. This year, at least, a reinforcement of BA.5 is probably our best bet to minimize infection, disease, and death during another likely winter hike.
“I fully hope that there will be an additional evolution in the coming months, but that this evolution will probably be added to 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 reduced to: vaccine compositions that can be manufactured in time for fall distribution, which we hope will generate the most [protection] against BA.4 / BA.5? ”