Will COVID boosters prevent another wave? Scientists aren’t so sure.

A Covid-19 vaccine event in Maywood, Ill., Sept. 13, 2022. (Jamie Kelter Davis/The New York Times)

As winter approaches and Americans increasingly huddle indoors without masks or social distancing, a combination of new coronavirus variants is causing a surge in cases and hospitalizations in counties across the country.

The Biden administration’s plan to stave off a national surge depends heavily on convincing Americans to take updated Pfizer-BioNTech and Moderna booster vaccines. Now some scientists are raising doubts about this strategy.

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The elderly, immunocompromised people and pregnant women should get the booster shots because they offer extra protection against serious illness and death, said John Moore, a virologist at Weill Cornell Medicine in New York.

But the picture is less clear for healthy Americans who are middle-aged and younger. They are rarely at risk of serious illness or death from COVID, and by this point most have built up immunity through multiple doses of vaccines, infections, or both.

The newer variants, called BQ.1 and BQ.1.1, are spreading rapidly, and boosters appear to do little to prevent infections from these viruses, as they are excellent at evading immunity.

“If you’re at medical risk, you should step up, or if you’re at psychological risk and you’re worried to death, go and get refreshed,” Moore said. “But don’t think this is going to give you some kind of amazing protection against infection and then go out and party like there’s no tomorrow.”

The latest boosters are “bivalent”, targeting both the original version of the coronavirus and the Omicron variants released earlier this year, BA.4 and BA.5. Only about 12% of adults have selected the latest download.

In an interview, Dr. Peter Marks, the Food and Drug Administration’s top vaccine regulator, acknowledged the limitations of the available data on the updated boosters.

“It’s true, we’re not sure how well these vaccines will do yet against preventing symptomatic disease,” he said, particularly as newer variants spread.

But, Marks added, “even modest improvements in vaccine response to bivalent boosters could have significant positive public health consequences. Since the downside is pretty low here, I think the answer is that we’re really supportive of people going out and considering getting this booster.”

Dwindling returns from involvement with Pfizer-BioNTech and Moderna vaccines require a new approach to fully protect Americans, Moore and other experts said. A universal vaccine that targets parts of the coronavirus that don’t mutate would be ideal, for example. A nasal vaccine may be better at preventing infections than an injection.

“Chasing variants by tailoring mRNA vaccines is not a viable strategy,” Moore said. “There is a need for better vaccine plans, but this needs a change of attitude at the government level.”

Recently, Pfizer-BioNTech and Moderna reported that their bivalent vaccines yielded antibody levels in study participants that were four to six times higher than those produced by the original vaccine.

But the companies were measuring antibodies against BA.4 and BA.5, not the rapidly accelerating variants BQ.1 and BQ.1.1. A series of preliminary studies suggests that the updated boosters, introduced in September, are only marginally better than the original vaccines at protecting against the newer variants — if at all.

The studies are small, based on laboratory tests and have not yet been reviewed for publication in a scientific journal. But the results from several groups are generally in agreement.

“It is unlikely that any of the vaccines or boosters, no matter how much you get, will provide substantial and lasting protection against infection,” said Dr. Dan Barouch, head of the Beth Israel Deaconess’ Center for Virology and Vaccine Research. who helped develop the Johnson & Johnson vaccine.

Designing a vaccine for an evolving virus is a formidable challenge. Pfizer, Moderna and federal regulators had to choose which variants of the coronavirus to target earlier this year so that enough vaccine could be made by the fall.

But the BA.4 is almost gone. BA.5 now accounts for less than 30% of cases and is rapidly declining. The BQ.1, on the other hand, has skyrocketed its numbers in Europe. This virus and its close relative, BQ.1.1, now account for 44% of coronavirus infections in the US.

In recent research, Barouch’s team found that BQ.1.1 is about seven times more resistant to the body’s immune defenses than BA.5 and 175 times more so than the original coronavirus.

“It has the most impressive immune escape and also grows at the fastest rate,” he said.

BQ.1 is expected to behave similarly.

By now, most Americans have some degree of immunity to the coronavirus, and it doesn’t surprise scientists that the variant that best evades the body’s immune response is likely to outcompete its rivals.

The new bivalent enhancer increases antibody levels, as any enhancer would be expected to do.

But the fact that the dose is divalent may not mean much. In August, a modeling study by immunologists in Australia suggested that any booster would provide additional protection, but that a variant-specific vaccine was unlikely to be more effective than the original vaccine.

“Most of the benefit comes from giving a booster dose, regardless of whether it’s a monovalent or bivalent vaccine,” the World Health Organization warned last month.

Studies have shown that most of the antibodies induced by a vaccine targeting BA.5, for example, still recognize only the original virus.

This is due to a phenomenon called “immune imprinting”, in which the body preferentially repeats its immune response to the first variant it encountered, despite being alerted to a newer variant.

“It’s easier for the immune system to go back to something it’s already seen,” says Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York. (Krammer has served as a consultant to Pfizer.)

Some experts have suggested that booster shots should be “univalent,” targeting only recent variants. Instead, the makers essentially halved the critical component of the new omicron-specific amplifier, undermining the reception’s effectiveness, they said.

But Krammer was more optimistic about boosters overall, despite the recent research. The new studies looked at the immune response immediately after vaccination, and the response may improve over time, he said.

“We’ll see with larger studies and studies at a later point in time if there’s a good or significant benefit, but I think it’s definitely not worse,” he added. “I don’t see much risk when you get the vaccine, so you might as well get the benefit.”

There may be ways to bypass immune imprinting — perhaps with a second dose of a bivalent vaccine based on the immune response after the first, as long as the second dose of the initial vaccine series boosted protection.

“What do we need to do right now to get through the next few months when I think we’re in another wave of the initial wave of COVID,” Marks said. “And then we have to look ahead and lean into how we’re going to do things differently moving forward.”

The FDA approved the boosters for use at least two months after a previous dose or infection. But stimulating again so soon may backfire, some studies suggest. Extending the interval between boosts to five or six months may be more effective, giving the immune system more time to improve its response.

Whatever the timing, adding yet another dose to the regimen seems unlikely to motivate Americans to opt for vaccination.

“Each new booster we come out with will have lower and lower intake, and we’re already pretty close to the floor,” said Gretchen Chapman, a behavioral health expert at Carnegie Mellon University in Pittsburgh.

The Biden administration may have no choice but to push through boosters given the lifting of other safeguards, Chapman said. But most people make decisions based on what others are doing in their social network, or what their political and community leaders recommend, not on internal scientific data, he noted.

“We shouldn’t spend a lot of political capital trying to get people to take this bivalent enhancer, because the benefits are limited,” he added. “It’s more important to vaccinate people who never had their initial round of shots than it is to get people like me to get their fifth shot.”

The Biden administration might have better luck convincing people to get boosters if other vaccines, such as Novavax or J&J, were available for that purpose, he added. This may be especially true for people who hesitated to get a booster shot because they had a strong reaction to an mRNA shot.

Even scientifically, it may make more sense to vary the body’s antibody response with different vaccines than to continue developing mRNA versions of vaccines, some experts said.

Marks said the FDA may recommend Novavax as a second booster after reviewing the data. Until then, this vaccine is only allowed as a first booster for people who are unwilling or unable to get an mRNA vaccine.

That rule “is completely ridiculous,” Moore said. “If the FDA’s goal is to increase vaccine uptake and boost immunity in the American population, why is it imposing such restrictions?”

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