Will constant vaccine boosters beat the coronavirus?

A year ago, just two doses of a Covid-19 vaccine — or even one, in the case of Johnson & Johnson’s formula — were considered sufficient protection against the coronavirus.

Today, faced with the extraordinarily contagious omicron variant, Israel has started offering fourth doses to some high-risk groups. On Wednesday, the US Centers for Disease Control and Prevention (CDC) extended the eligibility of boosters to teenagers and stopped describing people as “fully vaccinated” because two doses don’t seem more suitable.

Instead, a person’s immunization status will be “up to date,” or not. It’s no surprise that many Americans are asking themselves: When will this end? Will we have to roll up our sleeves to take boosters every few months?

Over and over again by a virus that defies expectations, scientists are hesitant to predict the future. But in interviews this week nearly a dozen of them said that, whatever happens, trying to beef up the entire population every few months is not realistic. It doesn’t make much sense scientifically either.

“It’s not uncommon to give vaccines periodically, but I think there are better ways than giving boosters every six months,” said immunologist Akiko Iwasaki of Yale University. Other strategies, she said, can “get us out of this eternally reinforcing situation.”

For starters, convincing people to queue up for injections every few months is likely a losing proposition. About 73% of adult Americans are fully vaccinated, but so far just over a third have opted for a booster.

“This certainly doesn’t seem like a sustainable long-term strategy,” said immunologist Deepta Bhattacharya of the University of Arizona.

Equally important, there is no data to support the effectiveness of a fourth dose of current vaccines. (The calculation is different for people with impaired immune systems, who may benefit from a fourth dose.)

Pfizer-BioNTech, Moderna and Johnson & Johnson said they are testing vaccines that target the omicron variant and could be available in a few months.

“It makes no sense to keep giving boosters against a strain that has already disappeared,” said Ali Ellebedy, an immunologist at Washington University in St. Louis. “If you’re going to give it one more dose after the third one, I’d definitely wait for an omicron-based one.”

If the goal is to bolster immunity against the micron or future variants, other tactics would be better than continuous boosters of a vaccine designed to recognize the original virus, experts say.

Some research teams are developing a vaccine called pan-coronavirus, designed to attack parts of the virus that would change very slowly or not at all.

Current vaccines could be combined with boosters from nasal or oral vaccines, which are better at warding off 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 could also bolster immunity, a lesson scientists have learned in fights against other pathogens.

Many experts were initially opposed to the idea of ​​a booster shot. Some believed that the original vaccination regimens would be enough to keep most people out of hospitals, and that this would be the true measure of a vaccine’s success.

Others felt it was unfair for rich countries to stockpile vaccines for booster shots when millions of people around the world had not yet received their first dose.

But the perspective changed when scientists saw the omnis fast and relentless march across the world. “The omicron really changed my thinking about it,” said immunologist Scott Hensley of the University of Pennsylvania.

“People who are vaccinated are really doing well in terms of hospitalization,” said Michel Nussenzweig, an immunologist at Rockefeller University in New York. Omicron made it clear that preventing all infections is a lost cause, he added.

If vaccines prevented infection and the spread of the virus, regular boosters would make sense. “But with the omnin, what good is it?”, said the scientist. “The endgame is to keep people out of the hospital.”

Last fall, Dr. Anthony Fauci, the US government’s top pandemic adviser, spoke repeatedly about the importance of avoiding symptomatic infections. But in recent days he’s also been saying that it’s the admissions that really matter.

To prevent infections, the timing of booster application must be precisely matched to the circulation of a variant in the population. Many people who received a third dose in early fall, for example, were vulnerable to the micron because their immune boost had already waned.

In general, people are advised to get vaccinated against influenza just before the virus begins to circulate in winter. If the coronavirus establishes a flu-like pattern, as seems possible, “you can imagine a scenario where we simply give boosters before winter every year,” Hensley said.

Some experts have raised concerns that receiving reinforcements too often — as some people are doing on their own — could even be harmful. In theory, there are two ways this can go wrong.

Most immunologists today dismiss the first possibility as unlikely, in which the immune system is depleted by repeated stimulation — a condition called “anergy” — and fails to respond to coronavirus vaccines. “We’re not really seeing these strange memory cells that indicate anergy or dysfunction,” said Bhattacharya.

The second concern, called “antigenic original sin,” seems more plausible. In this view, the immune system’s response is shaped to the first version of the virus, and its responses to subsequent variants are much less powerful.

With more than 50 mutations, the omicron is quite different from previous variants, and antibodies made to the original version of the virus struggle to recognize the latest version.

“We have enough clues that this could be a problem,” said Dr. Amy Sherman, a vaccine expert at Harvard University. “We certainly saw evolution in a short period of time.”

_{Translated by Luiz Roberto M. Gonçalves}