Most people ages 12 and older are considered “up to date” with their COVID-19 vaccines if they received either three doses of the mRNA shots from Pfizer-BioNTech or Moderna, or two doses of Johnson & Johnson’s Janssen vaccine. But some public health experts say another dose might be needed in the coming months.
On March 15, Pfizer and BioNTech requested authorization from the U.S. Food and Drug Administration (FDA) for a fourth dose of their vaccine in people ages 65 and older. In the past few days, Albert Bourla, Pfizer’s CEO, has said that he believes everyone will one day need a fourth dose in order to help prevent infections (a move that would have obvious benefits for the company’s bottom line.)
In order to authorize a fourth shot, the FDA will consider troubling signs that the immunity provided by the vaccines is starting to wane, which could make people more vulnerable to COVID-19’s more severe effects. Recent data published by the U.S. Centers for Disease Control and Prevention (CDC) show that protection against hospitalization for COVID-19 waned even after a booster dose of either the Pfizer-BioNTech or Moderna vaccines. From Aug. 2021 to Jan. 2022—a time span that includes waves of both Delta and Omicron variants—the booster was 91% effective at protecting against hospitalization in the first two months after people received it, but dropped to 78% four months after the shot. The vaccine efficacy against emergency room and urgent care visits for COVID-19 symptoms followed a similar decline, from 87% up to two months after the booster to 66% four to five months after the booster.
“We don’t know when you get to six months, seven months, or eight months after the third dose whether that 78% is going to go down to 60%, 50%, or 40%,” says Dr. Anthony Fauci, the White House’s chief medical advisor on COVID-19 and director of the National Institute of Allergy and Infectious Diseases. “For that reason, you are going to hear serious consideration for giving a fourth boost to the elderly and those with certain underlying health conditions. What we might be seeing in the reasonable future is that individuals, merely on the basis of age, and perhaps some underlying health conditions yet to be determined, would get an immediate boost.”
The CDC already recommends a fourth mRNA vaccine dose for people with weakened immune systems, including transplant patients and those undergoing chemotherapy for cancer, and other countries have similar guidelines. Israeli health officials have gone one step further; on Jan. 22, as cases and hospitalizations crept upward, the country authorized a fourth dose of the Pfizer-BioNTech mRNA vaccine for health care workers and people over 60 years old. The decision was based on early data from Israel’s Ministry of Health and researchers at several Israeli universities showing that among nearly a million vaccinated people over age 60, a fourth dose of the vaccine offered up to twice the protection against getting infected, and up to three times the protection against severe illness, compared to those who received three doses.
There is also growing evidence that all types of vaccine-induced protection continue to wane. Scientists have long known that the antibodies people make immediately after getting vaccinated are relatively short-lived, but the vaccine triggers the body to also produce other immune defenses, including T cells, which tend to be more durable. Even those responses, however, start to taper after several months, says Dr. Otto Yang, professor of medicine, infectious diseases, microbiology, immunology, and molecular genetics at the University of California, Los Angeles. That means existing vaccine regimens may need to be supplemented with yet another booster dose to keep both antibody and T cell numbers high enough to protect people from severe disease, he says.
But whether everyone needs an additional vaccine dose, and whether or not we can anticipate getting one every year or every few years, depends on what we want the vaccines to accomplish. The vaccines were not designed to prevent people from getting infected by the virus, but to protect them from getting extremely sick with COVID-19, and to keep them from needing hospitalization and intensive care. Remembering that goal, says Dr. Paul Offit, director of the Vaccine Education Center and professor of pediatrics at Children’s Hospital of Philadelphia, is useful when thinking about whether a fourth dose is necessary for most people.
“We got hung up using the word ‘breakthrough’ in describing mild illness,” he says, referring to the term for any infection occurring among vaccinated and boosted people (most of which were mild or even asymptomatic). “But that’s a win—it meant the vaccine was working for you and protected you from serious illness. We have developed a zero tolerance strategy that we are going to have to get over: the idea that it’s not okay to have mild illness after you’ve been vaccinated.”
If the goal of a COVID-19 vaccine is to protect people from severe disease, Offit says that there is still insufficient data supporting the need for a booster for most healthy adults. “I think we have to accept the notion that this is a three-dose vaccine in certain groups and a two-dose vaccine in others,” Offit says.
Offit, who serves on the FDA vaccine advisory committee of independent experts that reviews data and makes recommendations to the FDA about whether or not a vaccine is safe and effective, says that trying to protect the world’s population from mild disease with continued booster doses isn’t a realistic or practical public health goal. The question becomes one of balancing any marginal benefit in protecting against mild illness against potential side effects, which for the mRNA vaccines include the risk of inflammation of heart tissue. “Everything has costs, including boosting,” he says. “If it doesn’t benefit you in terms of protection against serious illness, then you have to consider the side effects.”
Fauci says health officials will be watching the hospitalization rate among vaccinated and boosted people closely in coming weeks and months; if it creeps upward, then it would signal a concerning waning of protection even against severe disease, which could warrant another booster dose. “We don’t know now if we are going to need it, but as long as this virus hangs around, I would not be surprised if we are going to need one more shot than we have had,” he says.
He and others also don’t anticipate continuing to boost as new variants crop up. Up to this point, that strategy came out of the urgent need to tamp down the virus as quickly as possible in as many people as possible. But it’s not a durable or practical game plan over the long term. “We’ve been chasing our tails with every variant, and we will perpetually be behind [the virus],” says Dr. Kirsten Lyke, professor of medicine at University of Maryland, who spearheaded studies about mixing and matching different types of COVID-19 vaccines.
But now that a good portion of the U.S. population has some degree of immunity through infection, vaccination, or both, the National Institutes of Health is launching new studies in search of a more targeted approach to potential booster shots. Rather than responding to new variants as they emerge and hoping the existing vaccines continue to protect against severe disease, scientists there are mapping out SARS-CoV-2’s mutations and trying to design vaccines against broad collections of changes that would ideally quell a number of different, but related strains that the virus may generate in the future. The study will involve up to 1,500 people at 25 sites. “By mid-summer, we would like to put all the data together so we can make a more scientific assessment as to whether additional boosters will work, whether we will need them, and which one we might need to use,” says Lyke.
Whether a fourth dose will be recommended for most Americans likely depends on future hospitalization rates among vaccinated and boosted people; if they continue to increase, that might push health officials to consider recommending another booster dose. In the meantime, Fauci says scientists at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center are investigating whether that additional dose should come from the same vaccine people have been receiving, or whether that additional dose should be with a new vaccine that targets a specific variant, such as Omicron. So far, the original booster produces similar immune responses to those generated by a variant-specific boosters in non-human primates. “Given the fact we have waning immunity, we may need a regular boost at intervals yet to be determined,” Fauci says.