What COVID Booster Shots Can and Can’t Do
The epidemiologist Céline Gounder discusses Pfizer boosters and the latest science on additional doses.
By Helen Rosner
September 23, 2021
In August, the White House introduced an ambitious plan to start providing booster doses of the covid-19 vaccines to all American adults. Even among the staunchly pro-vaccine, this announcement met with resistance. The two top officials in the F.D.A.’s Office of Vaccines Research and Review announced their plans to leave the agency after reportedly disagreeing with the White House’s approach, and the World Health Organization scolded the United States for considering administering third doses while poorer nations still have vaccination rates in the single digits. Critics argue that the data do not support the need for a third shot in most populations; exceptions include the elderly and the immunocompromised. On Wednesday, the F.D.A. authorized booster doses for those who completed their course of Pfizer vaccines more than six months ago, and who are over the age of sixty-five or otherwise at high risk, owing to health or occupation. A C.D.C. panel subsequently recommended excluding people on the basis of occupation, but the center’s director, Rochelle Walensky, overruled that guidance on Friday morning, saying that frontline workers, including doctors and teachers, should be eligible. (The C.D.C. also clarified the protocol for those with underlying health conditions: those over the age of fifty should get the booster; younger people should consult their doctor.) Once the C.D.C.’s director endorses the recommendations, people who are eligible for the booster doses can begin receiving them immediately.
This week, I spoke with Céline Gounder about the conflicting information about booster doses of the vaccine. Gounder is an epidemiologist and infectious-disease specialist at Bellevue Hospital and on the faculty of N.Y.U.’s Grossman School of Medicine, and was a member of the Biden-Harris transition team’s covid-19 advisory board. (In November of last year, Isaac Chotiner talked to her about efforts to contain the coronavirus’s second wave.) In the course of two conversations, which have been edited for length and clarity, we discussed which populations might benefit from a third shot, the best ways to prevent breakthrough infections, and the possible motives behind the Biden Administration’s approach to boosters.
When the White House endorsed universal booster shots a few weeks ago, many scientists and doctors—yourself included—were vocally unhappy. But if you look at, for example, the data coming out of Israel about declining vaccine effectiveness over time, it does seem like booster shots may be a solution.
What the data from Israel shows is that among older people—the studies define that as over the age of sixty—there is declining protection, from vaccination, against severe disease, hospitalization, and death. They did not see that decline in younger age groups. These are findings that have been replicated elsewhere: in the United Kingdom, in the United States, as well as in other countries, we’ve seen a similar pattern. It’s likely because older people’s immune systems are not as young and spry, just like their bones and joints are not young and spry, so their immune systems don’t respond as well to the vaccination.
What we’ve also seen, and this is typical of any vaccine, is that right after vaccination you get a big surge in antibody levels up front. But that’s not the only part of your immune system that kicks in; your immune system is forming a memory response, through memory cells. And so the antibodies may drift back down over time, but your memory cells are still there. Then, if you’re reëxposed to an infection, your memory cells kick into gear, and you get another surge of antibodies. The issue is that it takes three to five days or so for your immune cells to start revving up to make antibodies, and in that time the virus can still infect you and replicate—the incubation period with the Delta variant, for example, is about four to five days. Your immune system nips it in the bud before you get really sick, but you could still end up with a breakthrough infection.
That’s really how most vaccines work. They’re not preventing all infections—that’s what we call “sterilizing immunity,” and that’s actually quite rare. What most vaccines do is prevent the infection from taking off and making you sick. One of the problems with this whole debate around boosters is that people have had very unrealistic expectations of what vaccines can or can’t do. They think that seeing breakthrough infections is a failure of the vaccines, when it’s actually quite predictable and normal.
Does that mean boosters aren’t needed?
We’ve seen a clear loss of protection against severe disease, hospitalization, and death in three groups. In two of those groups—the elderly, and highly immunocompromised people—it’s because they don’t mount as strong of an immune response, and you have waning protection from there. So it makes sense to give them a booster dose. The hope is that it’s not just boosting their antibody levels but actually boosting their memory-cell response. That’s what’s going to protect them in the long term.
The other group in which a booster dose makes sense is the population living in long-term care facilities. This is the group where we’ve seen so many breakthrough cases, and it’s usually due to a caregiver or a visitor who is not vaccinated, who’s gotten infected in their community and is bringing the infection into the nursing home. This leads to breakthrough infections among vaccinated people in the nursing home. Nursing-home populations do tend to be older, and they’re more medically frail, so it’s already an intersection of age and high risk, medically speaking. And then you’re in this communal setting where a virus can spread easily.
That said, you’re going to get even greater protection from making sure caregivers and visitors in a nursing home are vaccinated. That helps reduce the risk of bringing the virus into that facility in the first place.
For people who aren’t in those populations, in your view, is a booster shot helpful?
If all you’re doing is temporarily boosting your antibody levels for three to six months, and then you’re right back to where you were in terms of your memory immunity, you haven’t really changed the long-term trajectory of your immunity. You really have to ask yourself: What are you trying to accomplish with that transient three-to-six-month boost in antibodies? There might be a case to be made for boosters if you have a massive surge and you can be very targeted with a particular population—say, Rikers Island, where there is a surge in transmission and infections. You could revaccinate everybody in the prison and put a stop to transmission. That’s quite literally a captive population. But when you’re talking about giving additional doses to the general population, you’re not really going to be able to have that kind of intense impact. You would have a much bigger impact by vaccinating people who are not vaccinated.
If the data are clear that there’s minimal advantage to these lower-risk groups, why has the White House been talking about universal boosters?
You can’t scale up vaccination infrastructure in a day—you need to be working with the folks doing the vaccinating. That means the big retail-pharmacy chains, big health systems, local and state departments of health, all the big players in terms of getting the work of vaccinating done. Some of those parties—in particular, the retail-pharmacy chains—had scaled up their vaccination workforce, and then they’ve since scaled it down, because they didn’t have the volume [of demand]. What I have been told is that [the White House messaging about boosters] is really about giving the vaccinators the lead time to scale up their workforce, and to prepare in terms of the places to vaccinate, supplies to vaccinate—not so much the actual vaccine, but all the other supplies—and to have all of those operational, logistical plans in place. [A White House spokesperson said that the messaging was based on “the independent recommendation of the nation’s top doctors at the Department of Health and Human Services.”]
Is there an explicit downside to getting an extra dose if you are not in one of these populations, or is it more that there isn’t a sufficient upside?
The downside is probably more theoretical. We have seen cases of myocarditis, which is heart inflammation, in younger men, typically in their teens and twenties, who’ve gotten either the Pfizer or Moderna vaccine. This has not led to permanent complications, but in the short term it can be unpleasant. We do not know if there may be increased risk of myocarditis with a third dose—it is very rare, so it would take a while to pick up on an increased risk. The other downside is cost, both in terms of the vaccine itself, and also in terms of all of the facility and manpower costs of getting people their booster dose.
And what is the upside? If you have already been fully vaccinated, there are diminishing returns on what that extra dose of vaccine will do to protect you, versus what it will do if it’s in the arm of somebody else in your community. You have to think about risk in terms of your risk reduction through vaccination, multiplied by the risk in the community. You as an individual will stand to benefit most by reducing risk in the community, if you’ve already been fully vaccinated. And the best way to do that is to vaccinate people who are not yet vaccinated.
That’s a question of the most efficient use of our supply of the vaccine.
And it is still a scarce supply, you know—not just in the United States, but around the world. Less than four per cent of people in Africa have been vaccinated, and that’s going to be the incubator for new variants, which will threaten our pandemic recovery. This is not humanitarian. This is not about generosity. This is pretty much about self-interest: if you are actually interested in getting on the other side of this, you have to start paying attention to people who are not vaccinated—not just here but in the rest of the world.
Now that Pfizer boosters seem imminent, people who got the Moderna or Johnson & Johnson vaccine want to say that they got Pfizer in order to get a booster. Some members of the C.D.C. panel seemed to support the idea of combining different vaccines.
Where we have the best data for mix-and-match is AstraZeneca, followed by either Pfizer or Moderna—it’s mostly out of Europe, where AstraZeneca is in use. AstraZeneca is most closely analogous to the Johnson & Johnson vaccine; they’re both adenovirus-vector vaccines. You do seem to get an even more potent immune response if you get a mix-and-match of AstraZeneca followed by Pfizer or Moderna. We think that will also be the case with Johnson & Johnson followed by Pfizer or Moderna, but we don’t know—that’s being studied by the N.I.H. right now.
Another very important question is whether you’ll get a similarly more potent immune response if you start with Pfizer or Moderna and then go to J. & J. We don’t know the answer to that; it’s still being studied. I know people are really impatient to get answers, but it’s difficult to do that in the absence of data. Sometimes we want to say, “Well, common sense says,” but the entire history of medicine is littered with what we think is common sense, and then we study it, and we realize actually it’s wrong.