A week after FDA and CDC advisory committees clashed on the nuances of when and whether to recommend COVID-19 booster shots, Anthony Fauci told my colleague Ed Yong that he still believes third doses of the mRNA vaccines are crucial, suggesting once again that they will eventually be part of a standard regimen.
As those committees deliberated, the experts considered qualitative evidence on the shots’ safety and efficacy, but also kept getting stuck on two larger conceptual questions. First: What, exactly, is the point of offering third shots? Skeptics of large-scale boosting argue that the COVID-19 vaccines were designed to prevent severe hospitalization and death, while third shots seem more likely to offer (temporary) protection against infection and mild disease. In their view, boosting wouldn’t offer any meaningful gains. “I reject that,” Fauci, who serves as Joe Biden’s chief medical adviser and the director of the National Institute of Allergy and Infectious Disease, said at The Atlantic Festival today. “I think we should be preventing people from getting sick from COVID even if they don’t wind up in the hospital.”
The second big question that tripped up the experts: Are third shots of an mRNA vaccine really boosters to remind our immune systems how to fight off the enemy, or are they essential for everyone to reach full protection? Put another way, can you be “fully vaccinated” without one? Fauci has previously suggested that third shots could become common practice, and today took an even stronger tack: “It is likely, for a real complete regimen, that you would need at least a third dose.”
In addition to booster shots, Fauci and Yong spoke about the Delta variant, global vaccine equity, and how the United States can prevent the next pandemic. Their conversation below has been lightly edited for length and clarity.
Ed Yong: In May, you said to The Washington Post that if 70 percent of adults were vaccinated by the fall, then we’re going to get out of the epidemic stage [of COVID] and much more into the control stage. Well, it’s now the fall. Around 65 percent of adults are vaccinated, but things don’t seem very controlled and hospitals are still struggling. Death rates are high. What went wrong?
Anthony Fauci: I’m not so sure anything went wrong. Something came onto the scene that made everything really very different: the Delta variant. We have about 70 million people in this country who still are not vaccinated. That is particularly problematic when you do that in the context of the Delta variant, which is really substantially more transmissible than what we were dealing with [in the spring]. I don’t think we should say, “Well, there’s nothing we could have done better,” but I don’t think you could say something went wrong.
These kinds of surges that we’re seeing regarding Delta are not isolated to the United States. I mean, the entire world virtually has been hit by this. So now that we are in this situation, how do we address it? We do know that the vaccines do work really quite well against Delta. There were breakthrough infections, but that’s because no vaccine is 100 percent effective. What they’ve done quite well thus far is prevent people from getting to the hospital and ultimately dying. So the bottom line is that we have within our grasp, within our power, the ability to have a major impact on what we’re seeing now with the numbers of infections. We’ve been well over 100,000 infections for quite a while now, and hospitalizations were up and deaths were up. Right now, it looks like we’re turning the corner a bit with a diminution in the number of cases and a diminution in the number of hospitalizations. Deaths are still going up, but that’s usually a lagging indicator of what’s going on in the community.
Yong: Many of the folks I’ve spoken to who work in public health and other disciplines have suggested that the U.S. has put too many eggs into the vaccine basket and, in some cases, traded them off against other interventions that are important. The move away from indoor masking in the spring, as one example; the continuing interferences in testing as another. Do you think that we have overemphasized vaccines at the expense of other strategies?
Fauci: I think we’ve placed a lot of emphasis on what is known historically and in real time now as a very high-impact, pharmacologic intervention in the form of a vaccine. Masking has really been a very complicated issue. The CDC made that change in the mask guidance at just the time when Delta was starting to really go up. I think now, if they were to look back at that decision, they would say, given the context of what Delta has done, that it likely should not have been the policy back then. In fairness to them, they quickly went back when we saw that Delta was really quite a formidable foe here. It would have been preferable had that been done earlier.
On the testing thing, you do have a point. I’ve always said that we should be flooding the system with easily attainable at-home testing so people can get a good feel for themselves, their families, their workplace about who is infected and who is not. Just the fact that we had very highly effective and safe vaccines should not make us move away from the intensity of testing. Testing is going to be very important, particularly when you have a virus [that will produce] breakthrough infections.
If the vaccine prevents you from getting sick, prevents you from losing work time, prevents you from getting to the hospital and prevents you from dying, that’s a really, really successful vaccine, even if you have a breakthrough infection. But if you do have a breakthrough infection, you are still capable of transmitting that infection to someone else. And that’s the reason why, among other reasons, we really need to do a lot of testing and make it very available. I mean, I have conversations with our British colleagues, and they are very much tuned in to making testing widely available to virtually anybody on their own at home or wherever [and making it] very easy accessibility- and price- and convenience-wise.
Yong: Do you think the U.S. can get to that point?
Fauci: I hope so. And I think we can, because we can’t be unidimensional in our approach to this outbreak.
Yong: You seem to be quite bullish about using boosters. And you’ve defended the administration’s decision to talk about widespread availability before the FDA had a chance to weigh in. What is your stance on the role that they should play in the pandemic going forward?
Fauci: First of all, Ed, let me put this in context. I believe that people need to understand that, at the time we’re giving boosters here and in other countries of wealth, it is important to make sure that we do more than just pay attention to the developing world, that we give them enough resources, enough doses, and enough capability to make vaccines. I believe we can do both, and we shouldn’t do our boosters at the expense of getting vaccines to the developing world.
Having said that, I’ve made it clear that my opinion has always been that I believe that a third-shot booster for a two-dose mRNA [vaccine] should ultimately and will ultimately be the proper, complete regimen. The vaccine is very successful. The durability of it is something that’s a subject of considerable discussion and sometimes debate.
I supported and continue to support what the FDA did on the basis of the information they had and on the advice of their advisory committee. I support what the CDC has done, and I think that Dr. Walensky made a very good, informed, and courageous choice. She took the advice of the [Advisory Committee on Immunization Practices] under advisement and she made a modification.
As a physician and as a scientist and a public-health person, I think it is not entirely correct to make this very strong dichotomy between waning protection against hospitalization and death and waning immunity against infection and mild-to-moderate disease. It is an assumption that it’s okay to get infected and to get mild-to-moderate disease as long as you don’t wind up in the hospital and die. And I have to be open and honest: I reject that. I think we should be preventing people from getting sick from COVID even if they don’t wind up in the hospital. Ultimately I believe that the optimal regimen for the mRNA [vaccines] is going to include that third booster shot.
Yong: And do you feel that that’s been communicated, the idea that the whole plan was always going to be three doses?
Fauci: We did not always know that a third dose would likely be an important part of the proper, complete regimen. In the early trials, we started off with a prime followed by a booster. And the results were so strikingly good, both in the animal model and in the Phase 1, Phase 2 trials, that we didn’t have the luxury to say, “Wait a minute, we’re going to try multiple different doses and make sure we get it just right.” We were in an emergency situation, so we went with what was really good. Already the track record has shown you that it has saved millions of lives.
What we did not fully appreciate—and there was no way of knowing it—is what the durability of that would be. I’m an immunologist, and I know what other immunologists say is true: The antibody level going down doesn’t necessarily mean that you’re not protected, because you have memory B cells; you have T cells. But the clinical phenomenon is the thing that you need to pay attention to. And that’s what we were seeing: Over time, protection against hospitalization was going down, starting off with the elderly and then even occurring across age groups. Without a doubt, the protection against clinically recognizable disease was going down.
We did not know that during the clinical trials. What we’re starting to see now and fully appreciate is that it is likely, for a real, complete regimen, that you would need at least a third dose. Now, the question is going to be, does that mean we have to boost people every single year? We don’t know that now. What I hope is going to happen is that this is going to get to the human immune system, in vaccinated people, that degree of maturation of response, that will really give much more durability to it.
Yong: A lot of other scientists and health experts have said that focusing on an incremental gain for immunity for people who have already been vaccinated works against the goal of broadly immunizing the rest of the world. You’ve said that we can have both of those two things together. Why do you believe that to be the case? And if that is the case, then why haven’t we made better progress with global vaccine equity to this day?
Fauci: My feelings and my track record on global equity and global accessibility are available for anybody to examine. So I do feel that we have that obligation. On the issue of one dose versus two doses: [It’s not an issue] if you have enough; that only becomes an issue when you really do have a scarcity of doses. But when you have enough doses, you should go with the full regimen at the time. Experience has shown us that although there is some protection and there’s no doubt about it, you can’t get by with one dose. It is not adequate. And we have seen various people who have been vaccinated with a single dose to not have nearly as much or even adequate protection. They have some protection. But if you look at studies comparing one dose versus two doses in multiple different parameters of infection—of getting infected with variants, of clinical disease, of hospitalization—you do get some protection with one dose, but it is not nearly as good as two doses. And that’s the reason why we wanted to make sure, to the best of our ability, we get people vaccinated with both doses.
Yong: We talked about pandemics and preparing for them back in 2018, well before COVID. You and many others told me about these cycles of panic and neglect where a crisis hits, everyone pays attention, investments flow, and then inevitably our willingness to do what is necessary to prepare against future pandemics slips. Do you think that we’re destined to repeat that cycle? What can the U.S. be doing right now to avert tomorrow’s pandemics?
Fauci: I have been in the unfortunate situation of having lived through multiple cycles of the phenomenon that you are just now describing, of semi-panic and promising that we will not let this kind of thing happen again. We’ve been through HIV, and we’ve been through pandemic flu, and we’ve been through Zika, and we’ve been through Ebola—and now we have a historic outbreak with COVID-19. I really do sincerely hope, having been through all of that myself personally, that we will not allow what we’ve been through over the last 20 months to slip from memory, which means we have to, and we are starting right now to, prepare for the next pandemic. I think what we’ve learned now is that, given the jumping of viruses from one species to another—what we’ve seen with Ebola, HIV, SARS-1, MERS—we’ve got to be prepared from multiple standpoints.
Pandemic preparedness is not unidimensional. It’s everything from global cooperation to communication to surveillance, both at the animal level and the human level, to have a basic and fundamental clinical-research endeavor where you’re able to do things like take a pathogen, recognize it, and get vaccines ready to go into people. That’s what we’re talking about now. We’re talking about tens of billions of dollars that will be needed. I really do hope that when we get through this, which we will, we don’t then start focusing and concentrating on another problem that takes our mind off this extraordinarily difficult period that we will have lived through.
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