人人都需要打第四针加强针疫苗吗？

It’s a good news and bad news situation. The boosters work, but they probably fade.

So do we need more? And how many more doses of COVID vaccines will we have to take?

Amid the Delta wave last September, the Centers for Disease Control and Prevention announced it was recommending COVID vaccine booster shots only to people over 65 or with underlying medical conditions.

Fast forward six months, and the game has changed. The highly-contagious Omicron variant, first detected in South Africa last November, has spread fast and furious throughout the world, and public health officials in the U.S. and Europe have recommended booster shots for all adults.

But is this enough?

Data from the CDC shows that third shots can be as much as 90% effective at preventing hospitalization from Omicron, especially in older adults. But immunity granted from boosters may wane as early as four months after taking the third shot, according to a recent CDC study. To guard against this and future variants, should we be expecting recommendations to take fourth, or even fifth doses?

“We've been surprised by this virus multiple times and we've been overconfident about having solved things multiple times. We need to remain in a position to pivot rapidly if we need to,” Dr. John Wherry, director of the Institute for Immunology at the University of Pennsylvania, told Fortune.

For Dr. Wherry, that means keeping options on the table, including future boosters, for whatever circumstances arise.

Missing data

The pandemic and the SARS-CoV-2 virus that fueled it has left pretty much every scientist scratching their heads. There are so many things we still do not know. Where did the virus emerge from? Why does it make some people so much sicker than others? Why are so many cases asymptomatic? And of course, how long do the boosters last?

“Unfortunately, the data is not quite there yet,” Dr. Trina Racine, associate director for vaccine development at the Vaccine and Infectious Disease Organization, told Fortune about the science behind the length of booster immunity.

“There is some preliminary data that would suggest our immune responses to third doses do start to wane over time, just like we saw with two,” Dr. Racine said. “That would suggest fourth doses may be necessary.”

Public health officials, including Dr. Anthony Fauci, have begun to tout the possibility of further doses, at least for some segments of the population, should more data on the immunity of third doses come in.

"It's entirely conceivable that we might [need fourth doses],” Fauci said in January. “But I think before we rush to a fourth dose, I would be careful to see what the result of the third dose is."

Even with missing data, some scientists are cautiously optimistic, at least for now, that we will avoid a scenario in which a new vaccine booster is required every six months to maintain a defense against the virus. But it might still be annual.

“Hopefully it’ll be more like a flu shot where you have to get it once a year,” Dr. Racine said. “Six months is pretty frequent.”

“In the absence of a real concerning new variant that escapes preexisting immunity, much worse than even Omicron, I think boosters every six months would be unlikely,” Dr. Wherry agreed.

Targeted boosters for vulnerable groups

Even though most scientists eagerly await more data to come in, some countries are moving forward with recommending a fourth vaccine booster shot for specific groups of vulnerable people.

In the U.S., the CDC has recommended that all adults who are moderately or severely immunocompromised receive a fourth dose. In Europe, several countries are still discussing how to recommend fourth doses and to which groups of people, while Sweden began recommending fourth doses to all citizens 80 and over on February 14.

Targeted approaches to future doses may become the norm soon in more countries.

“I could see, especially in older populations where immunity maybe didn't reach the same high levels as in younger, healthier populations, fourth doses may be required sooner,” Dr. Racine said.

Dr. Wherry agreed that targeted recommendations for certain groups could become commonplace. “Elderly people have two issues,” he said. “One, vaccines don't work as well, and two: you don't get as high of an antibody response initially. We want to try to keep those antibody levels up for as long as we can.”

But it’s important to keep in mind that youth does not necessarily translate to less severe forms of the disease, and depending on how COVID is circulating, booster shots may still be necessary for younger and otherwise healthy people.

“It's going to depend on circulating levels around the world and the likelihood of new variants coming out,” Dr. Racine said. She believes that even if more boosters are not required for all adults now, that does not exclude the possibility that they will be in the future.

Dr. Wherry agreed that any future public health measures will depend on how the virus evolves and how it is circulating, maintaining that booster shots may continue to be necessary in order to protect older and immunocompromised groups.

“The real need for a third dose or even a fourth dose is to protect the elderly, people who are immunocompromised and at high risk,” he said, adding that “part of what we want to try to achieve with boosters is to limit community spread, to help keep our businesses and schools open and start to move towards a general reopening of society.”

Liberties and alternatives

It’s possible, even likely, that we will reach a different stage of the pandemic in which governments feel the need to exercise caution and urge more people to get boosted.

“The role of the government is to provide life, liberty and pursuit of happiness to its people,” Dr. Jerome Kim, director general of the International Vaccine Institute, told Fortune. “Its role is to preserve life, understand the liberties and put into place the level of protection that is needed.”

But it remains unclear whether a majority of the population will follow through on those pleas.

Protests against vaccine mandates and anti-COVID restrictions are sweeping Canada, the U.S, France, and Belgium. While many people were willing to adjust their lifestyles earlier in the pandemic, it is becoming increasingly difficult for governments to ask their citizens to do so.

Countries have already started to roll back masking and COVID restrictions in the U.S. and Europe, while many more are loosening their entry and quarantine requirements for new arrivals, as a growing portion of the world begins trying to live with the virus.

Experts agree that boosters may become recommended to certain segments of the population, but boosters alone are not what will end the pandemic.

“We think of our response like a defense,” Dr. Kim said. “The first line of defense were the things that worked in the beginning like mask wearing and distancing. The second line of defense is to vaccinate.” If cases trickle past both of these defense lines, then the final weapon in our arsenal, according to Dr. Kim, are therapeutic medicines that can reduce the risk of getting seriously sick, even if one contracts the disease. “[Therapeutics can] keep people out of the hospital, keep them from dying,” Dr. Kim said.

Boosters are important, especially for some people, but therapeutics that can prevent deaths and instances of severe disease, such as monoclonal antibodies or Pfizer’s recently approved Paxlovid drug, are just as important to ending the pandemic, experts say.

“I would rather prevent myself from getting sick, versus having the option of taking a pill if I do. But I think both are necessary,” Dr. Racine said.

“The vaccines are working, they're doing their job,” Dr. Wherry said. “What we need are therapeutics for when people do get infected so that we can intervene early and shift the balance and outcome.”