Will anti-covid boosters stop another wave? Scientists are not so sure

As winter approaches and Americans increasingly gather indoors without masks or social distancing, a mix of new coronavirus variants is driving increased cases and hospitalizations across the United States.

The Biden administration’s plan to prevent a nationwide surge relies heavily on convincing Americans to get updated booster shots of the Pfizer-BioNTech and Moderna vaccines. Now, some scientists are raising doubts about that strategy.

Elderly adults, immunocompromised people and pregnant women should get 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 middle-aged and younger Americans. They are rarely at risk of serious illness or death from Covid, and by this time, most have developed immunity through multiple shots of the vaccine, infections, or both.

The most recent variants, called BQ.1 and BQ.1.1, are spreading rapidly, and boosters seem to do little to prevent infections with these viruses, as they are excellent immunity evaders.

“If you are medically at risk, you should get a booster, or if you are psychologically at risk and you’re worried about death, go and get a booster,” Dr. Moore said. “But don’t believe it will give you some kind of incredible 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 that circulated earlier this year, BA.4 and BA.5. Only about 12% of adults opted for the latest vaccine.

In an interview, Dr. Peter Marks, the FDA’s chief vaccine regulator, acknowledged the limitations of available data on the updated boosters.

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

But, Dr. Marks added, “even modest improvements in vaccine response to bivalent boosters can have important positive public health consequences. Since the downside is very low here, I think the answer is that we really approve of people considering taking the booster.

Lower returns from modifications to the Pfizer-BioNTech and Moderna vaccines call for a new approach to protecting Americans at large, Dr. Moore and other experts said. A universal vaccine that targets parts of the coronavirus that do not mutate would be ideal, for example. A nasal vaccine may be better for preventing infections than an injectable one.

“Chasing variants by adapting mRNA vaccines is not a sustainable strategy,” said Moore. “There is a need for better vaccine designs, but this requires a change in attitude at the government level.”

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

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

The studies are small, based on laboratory tests, and have not yet been approved for publication in a scientific journal. But results from various teams generally agree.

“It’s not likely that any of the vaccines or boosters, no matter how many you take, will offer substantial and sustained protection against infection,” said Dr. Dan Barouch, head of the Beth Israel Deaconess Center for Virology and Vaccine Research, which helped develop Janssen’s vaccine.

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

But the BA.4 variant has all but disappeared. BA-5 now accounts for less than 30% of cases and is declining rapidly. BQ.1, on the other hand, sent the numbers skyrocketing in Europe. This virus and its close relative, BQ.1.1, now account for 44% of coronavirus infections in the United States.

In recent research, Dr. Barouch’s team found that BQ.1.1 is approximately seven times more resistant to the body’s immune defenses than BA.5 and 175 times more resistant than the original coronavirus. “It has the most impressive immune evasion and is also growing the fastest,” he said. BQ.1 is expected to behave in the same way.

By now, most Americans have some degree of immunity to the coronavirus, and it comes as no surprise to scientists that the variant that best evades the body’s immune response is likely to outperform its rivals.

The new bivalent booster increases antibody levels, as you would expect from any booster.

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

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

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

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

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

Some experts have suggested that the boosters should have been “monovalent”, simply targeting recent variants. Instead, manufacturers effectively halved the crucial omicron-specific component of the new booster, undermining the injection’s effectiveness, they said.

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

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

There may be ways to prevent immune imprinting, perhaps with a second dose of a bivalent vaccine that builds on the immune response after the first, just as the second dose of the initial series of vaccines consolidated protection.

“It’s what we need to do now to get through the next few months when I think we’re in yet another incipient wave of Covid,” said Dr Marks. “And then we need to look forward and assess how we’re going to do things differently going forward.”

The FDA authorized the use of boosters at least two months after a previous dose or infection. But reinforcing too soon can be counterproductive, some studies suggest. Increasing the interval between boosters to five or six months may be more effective, giving the immune system more time to refine its response.

Whatever the timing, it seems unlikely that adding an injection to the regimen will motivate Americans to opt for immunization.

“Each new booster we release will have less and less uptake, and we’re pretty close to the bottom,” said Gretchen Chapman, an expert in health behavior at Carnegie Mellon University in Pittsburgh.

The Biden administration may have no choice but to step up reinforcements due to the lifting of other precautions, said Dr. Chapman. But most people make decisions based on what others in their social network do or what their political and community leaders recommend, not on esoteric scientific data, she noted.

“We shouldn’t spend too much political capital trying to get people to get this bivalent booster, because the benefits are limited,” he added. “It is more important to vaccinate people who have never received the initial series of vaccines than to have people like me receive the fifth shot.”

The Biden administration may have better luck convincing the public to receive boosters if other vaccines, such as Novavax or Janssen, are available for that purpose, she added. This may be particularly true for people who have been hesitant about getting a booster shot because they had a strong reaction to an mRNA vaccine.

Even from a scientific perspective, it may make more sense to diversify the antibody response with different vaccines than to continue to roll out versions of mRNA vaccines, some experts said.

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

That rule “is completely ridiculous,” Moore said. “If the FDA’s goal is to increase vaccine acceptance and boost population immunity, why is it putting restrictions like this?”

^{Translated by Luiz Roberto M. Gonçalves}