Will ‘forever boosting’ beat the coronavirus?

Everyone should get a booster shot. In the long run, though, doses every few months aren’t a viable public health strategy. Experts in healthcare have also emphasised that the strategy makes little scientific sense

APOORVA MANDAVILLI

Ayear ago, just two doses of a COVID-19 vaccine — or even one, in the case of Johnson & Johnson’s formulation — were thought to offer sufficient protection against the coronavirus. Now, faced with the extraordinarily contagious Omicron variant, Israel has begun offering fourth doses to some high-risk groups. On Wednesday, the Centers for Disease Control and Prevention expanded eligibility for boosters to adolescents and backed away from describing anyone as “fully vaccinated” because two shots no longer seem adequate. Instead, one’s vaccination status will now be “up to date” — or not. It’s no surprise that many Americans are wondering: Where does this end? Are we to roll up our sleeves for booster shots every few months? Humbled repeatedly by a virus that has defied expectations, scientists are reluctant to predict the future. But in interviews this week, nearly a dozen said that whatever happens, trying to boost the entire population every few months is not realistic. Nor does it make much scientific sense.

“It’s not unheard-of to give vaccines periodically, but I think there are better ways than doing boosters every six months,” said Akiko Iwasaki, an immunologist at Yale University. Other strategies, she said, could “get us out of this forever-boosting kind of a situation.”For starters, persuading people to line up for shots every few months is probably a losing proposition. About 73% of American adults are fully vaccinated, but so far just over a third have opted for a booster.

“This doesn’t seem to be a sustainable longterm strategy, for sure,” said Deepta Bhattacharya, an immunologist at the University of Arizona. Just as important, there are no data to support the effectiveness of a fourth dose of the current vaccines. (The calculus is different for people with impaired immune systems, who might well benefit from a fourth dose.) Pfizer-BioNTech, Moderna and Johnson & Johnson have all said that they are testing vaccines targeting Omicron that may become available in a few months.“It doesn’t make sense to keep boosting against a strain that’s already gone,” said Ali Ellebedy, an immunologist at Washington University in St. Louis. “If you are going to add one more dose after three, I would definitely wait for an Omicron-based one.”

If the goal is to boost immunity against Omicron or future variants, other tactics would be better than continual boosts of a vaccine designed to recognize the original virus, experts said. Some research teams are developing a so-called pan-coronavirus vaccine designed to target parts of the virus that would change very slowly or not at all.

The current vaccines could be combined with boosters of nasal or oral vaccines, which are better at preventing infection because they coat the nose and other mucosal surfaces — the entry points for the virus — with antibodies. And simply allowing more time between vaccine doses might also strengthen immunity, a lesson scientists learned in fights against other pathogens. Many experts were initially opposed to the idea of a booster shot at all. Some believed the original vaccine regimens were enough to keep most people out of the hospital, and that this should be the true measure of a vaccine’s success. Others felt it was unfair for wealthy countries to hoard the vaccine for booster shots when millions worldwide had yet to receive a first dose. But the perspective shifted when scientists saw Omicron’s rapid and unrelenting march across the world. “Omicron really did change my thinking about this,” said Scott Hensley, an immunologist at the University of Pennsylvania.

“People that are vaccinated really are doing very well in terms of hospitalization,” said Michel Nussenzweig, an immunologist at Rockefeller University in New York. Omicron has made it clear that preventing all infections is a lost cause, he added. If the vaccines prevented infection and spread of the virus, regular boosters might make sense. “But with Omicron, what’s the point?” Nussenzweig said. “The endgame is keeping people out of the hospital.”

Last fall, Dr. Anthony Fauci, the nation’s top pandemic adviser, repeatedly spoke of the importance of preventing symptomatic infections. But in recent days he, too, has been saying that it is hospitalizations that truly matter. In order to prevent infections, booster shots must be exquisitely timed to a variant’s circulation in the population.

Many people who got a third dose early in the fall, for example, were left vulnerable to Omicron because the immune boost had already subsided. Generally, people are told to get vaccinated against influenza just before the virus starts circulating in winter. If the coronavirus settles into a flu-like seasonal pattern, as it seems possible, “you can imagine a scenario where we simply give boosters before the winter each year,” Hensley said.

Some experts have raised concerns that getting boosters too often — as some people are doing on their own — may even be harmful. In theory, there are two ways in which it could backfire. Most immunologists now dismiss as improbable the first possibility, in which the immune system is exhausted by repeated stimulation — a condition called “anergy” — and stops responding to coronavirus vaccines. “We’re not really seeing these weird memory cells that are indicative of anergy or dysfunction,” Bhattacharya said.

The second worry, called “original antigenic sin,” seems more plausible. In this view, the immune system’s response is tailored to the first version of the virus, and its responses to subsequent variants are much less powerful. With more than 50 mutations, Omicron is different enough from previous variants that antibodies made for the original version of the virus struggle to recognize the latest version.“We have enough clues that it could be a problem,” said Dr. Amy Sherman, a vaccine expert at Harvard University. “We’ve certainly seen evolution in a short period of time.”