On November 29, a few days after South African scientists issued their first report on the Omicron variant, the CDC called for all adults to get a booster shot. The decision was based on the earliest data available on Omicron, which offered a preview of the variant’s ability to erode the protection of vaccines and prior infection, leading to increased transmissibility.
But not everyone agreed. As a member of the FDA’s vaccine advisory committee, Dr. Paul Offit, a professor of pediatrics at Children’s Hospital of Philadelphia, had not supported widespread boosting at the committee’s meetings in September and October when the agency authorized boosters for all adults. On the same day the CDC strengthened its recommendation, Offit co-authored an op-ed in the Washington Post with two former top officials in the FDA’s office of vaccine research who reportedly resigned in the fall in part because of their opposition to the FDA’s authorization of boosters for all. The trio wrote that they were in favor of boosters for people at high risk of serious illness, and those who might be in regular contact with the vulnerable, but they made an argument against boosters for all, writing that the focus on boosting interfered with vaccination campaigns and that vaccines continued to be extraordinarily effective, even against Omicron, which was in its infancy. Intelligencer called Offit to ask him about the latest data on Omicron and vaccines.
You’ve been vocal about your opposition to the idea that boosters can provide a path out of the pandemic. Has the latest data on Omicron changed anything for you?
The evidence that we have so far is that protection against severe disease induced by two doses of an mRNA-containing vaccine — all of the data are obviously with Pfizer — is that you’re going to be protected against serious illness, meaning the kind of illness that causes you to go the doctor’s office, the hospital, or the ICU. And that’s what you would expect based on the other variants. The protection against serious illness is mediated by immunological memory cells, T-cells. Even though the virus’s spike-protein level drifts and mutates, the T-cells are conserved. So you’re seeing exactly what you would expect.
I think what’s different with Omicron is that you’re not as well protected against mild illness. So the question is: What does the booster buy you? It buys you better protection against mild illness. But then the question becomes: For how long? Unlike protection against serious illness, which is mediated by memory cells that are long-lived, protection against mild illness is mediated by neutralizing antibodies that are not as long lived.
So why are so many people insistent on recommending or requiring boosters for everyone?
I think where we got seduced here was with the Phase III trials a year ago. When Pfizer and Moderna did those Phase III trials, they found that protection against mild illness was 95 percent. That’s remarkable. The reason it was remarkable is that those were three-month trials, so all of the participants had recently received their second doses. That wasn’t going to last. People started talking about boosters when they saw fading immunity, even though it is what you would expect — it was fading immunity against mild illness or asymptomatic infection, but protection against serious illness held up.
I’m not opposed to booster dosing. What I think we need to make clearer is why we’re boosting. There is certainly a value to boosting people who are older or people who live in long-term-care facilities. The question is, if we’re saying that healthy, young people need a booster dose, which is what we’ve just said, I think we need to explain to the American public that we’re getting prevention, for the most part, against mild illness, and it might not be long-lived. In all likelihood, even after a third dose, eventually antibodies will fade.
The question, as I’ve said, is for how long? I think we’ve confused people about what it means to be fully vaccinated. On the one hand you have the CDC recommending a booster dose for everybody over 18, which was rejected twice by the FDA’s vaccine advisory committee and the CDC’s advisory committee, and then on the other hand you have research institutes, universities, colleges, and hospitals that now have three-dose mandates while others have two-dose mandates. We’ve confused people.
Isn’t any reduction in protection against mild illness, extrapolated over the entire population, going to be very burdensome on our hospital system?
What’s burdensome to the hospital system are people who are unvaccinated. I’m just coming off a one-week rotation at Children’s Hospital of Philadelphia and I’m rotating through the COVID ward. During the week I was on service, of the 17 or 18 children we admitted — most of whom were over 5, many of whom were over 12, a handful of whom went to the ICU — what they all had in common was that none of them were vaccinated. Neither were their parents and siblings. That’s the problem. We could talk endlessly about booster dosing, or monoclonal antibodies, or antivirals, but we need to find a way to vaccinate the unvaccinated because that’s the heart of this pandemic. That’s who spreads this virus, that’s who generally gets hospitalized. If you talk to people who work in hospitals, they will tell you the same thing, which is that boosting the vaccinated is not our way out of this.
You had expressed some concern over “original antigenic sin,” saying that some people may want to wait until a booster is customized to target a specific variant. Is that still the case?
Take someone who has had two doses of vaccine, and who has a mild illness, and compare them to someone who didn’t get any vaccine but has a mild illness. The person who is vaccinated will shed less virus for a shorter period of time. That’s based on a couple of studies. The question then becomes, will you move the needle on this pandemic by boosting the vaccinated? Will you in any significant way decrease shedding and therefore decrease contagiousness and therefore decrease spread by giving a third dose to somebody who has already gotten two doses? The CDC had a slide on this that said it was to be determined. We’ll see whether this makes an impact on the community.
Maybe I’m wrong, but I feel like by constantly discussing booster dosing we’re not talking about the thing that’s really going to get us out of this: vaccinating everyone. Maybe it’s because we’ve given up, but I don’t think we should give up. I have to believe there’s some way to make this happen.
Fifty percent of vaccinated Americans have already received a booster. That’s something like 30 percent of the U.S. population. You’ve said there is evidence of that benefiting people medically, but what about a public-health benefit?
I hope so. We’ll see. Well, I guess we won’t see because we’re not doing any sort of controlled experiment on this, we’re just getting people who have already gotten two doses to get a third dose. You don’t have any trouble scaring people who have already gotten two doses to get a third dose, or a fifth dose. We’re in. It’s the other group that you worry about. You should have had my experience last week in the hospital. Not one child was vaccinated. They all could have been vaccinated. Not one of those parents was vaccinated. You’re watching children getting wheeled up to the ICU, sedated, a tube put down their windpipe, attached to a ventilator, parents are crying. No one’s vaccinated. It’s just frustrating.
What about people who are worried about long COVID from a mild infection?
Because Omicron does have a number of mutations in the receptor-binding domain, I think that two doses of Pfizer vaccine will not be as effective at preventing mild illness, even if you’ve just gotten your second dose, as it was against Alpha or Delta or the other variants. I think you’re less protected against mild illness. Some people would argue they don’t want to suffer mild illness because they may go on to develop long-term COVID, or they may feel they are more likely to develop serious infection because Omicron is more contagious — no vaccine is 100 percent effective against serious illness. That all makes sense, but realize that you’re probably only buying a limited period of time during which you’re boosting those antibodies and then lessening your risk of mild infection.
Dr. Fauci’s point was that were this not a pandemic, this would have always been a three-dose vaccine, meaning that the best way to induce memory is to have three doses. That’s true for other vaccines. That’s true for inactivated bio-vaccines, like the polio vaccine. It’s true for purified-protein vaccines like the hepatitis B vaccine. But we don’t have any evidence for that yet in the United States. To date, the vaccines’ two doses appear to still protect against serious illness. So right now, it’s not a three-dose vaccine, it’s a booster dose. So which is it? A three-dose series because it gives us the highest frequencies of memory cells and the best protection against disease? Or is this a booster dose because we’re trying to boost the neutralizing antibodies and lessen mild infection? I just think we need to explain to the American public what it is we’re trying to do with this vaccine.
How long until we have enough data to know which one of those explanations makes sense?
It should be very soon. A few days ago Dr. Rochelle Walensky said we had 40 cases of Omicron and of those 40 cases, 10 hadn’t been vaccinated. Of the other 30 people, some had received two doses and some had received three doses. Okay, well, that 40 will become 400, and then 4,000. Then you should have a very good idea as to whether or not that third dose really makes a difference and how virulent Omicron is in the unvaccinated, not previously infected person. It is incumbent upon the CDC to generate those data to prove that it’s important to get that third dose as compared with the second dose.
More on omicron
- What to Know About the New COVID Booster Shots
- The Dismantling of Hong Kong
- What We Know About All the Omicron Subvariants, Including BA.2.12.1
