鶹ý Editor-in-Chief Marty Makary, MD, MPH, of Johns Hopkins in Baltimore, discusses T cells and what they mean for COVID-19 resistance with , of the Department of Microbiology and Immunology at Columbia University in New York City.
Following is a transcript of their remarks; note that errors are possible.
Makary: Hi, I'm Marty Makary with 鶹ý. I have the privilege of being here today with Dr. Racaniello from Columbia University, a professor of virology. Vincent, great to be with you. Thanks for joining us.
Racaniello: Thank you for having me.
Makary: You've done a lot on coronavirus and you've been speaking up on the issue. Thanks for sharing your expertise. I'm particularly interested in some of your thoughts right now, as it relates to this idea of, will we need boosters down the road. It's obviously an unknown, but something I think people like you might have some more wisdom on than others.
Racaniello: It's a good question. You know, at the beginning of the outbreak we would've said no, because we didn't think that coronaviruses changed like flu does. Influenza viruses changed regularly.
Sometimes we need a new vaccine every year or every 2 years. And I would have said, if you asked me a year ago, I would have said, nah, we don't need a new vaccine because coronas don't change. But boy, have I been proven wrong and many other people. They do change.
And so, you know, as we see variants have been arising with changes in the spike, and some of these variants do decrease the ability of antibodies in people's blood to block infection. And, you know, as more and more people are infected, more and more variants arise.
We don't know what the end game is there. But yeah, it's possible that we might, at some point need to reformulate the vaccine perhaps every year or so to match whatever is circulating.
However, as far as this year goes, many of the vaccines are actually good at preventing serious disease and death, even in areas where variants are circulating. And I think the important lesson there, and this is really what I want to emphasize, is that, when you get these vaccines, you make antibodies against spike. Most of them are spiking-encoding vaccines.
But you also make T-cells. And those have been kind of ignored in the narrative. And it turns out that the variants do not change the parts that T-cells recognize. And T-cells will eliminate infected cells in your body. And that's why the vaccines actually prevent hospitalization and death, even when there are variants circulating.
So how long that will hold up, that's the question. And that will determine whether we have to reformulate. And if so, how often.
Makary: I really wanted to get your opinion on this because first of all, I don't know, but when I hear the companies talk about it and they're making their rounds right now, talking about it as if it's a certainty, I wonder if they're trying to set expectations in case we do need the boosters. And really, is it a 50-50 thing, we just don't know? Is it that we may be as likely to need a booster every year as we would ever say, 3 to 5 years or, in the world of predicting, is the rate of mutation really evading vaccinated immunity in preventing those key outcomes that much that you think it's going to be annual?
Racaniello: Well, you know, so far we've seen quite a few variants arising in different countries. So the reason for that is that every human population is slightly different genetically, we're all outbred.
So that's not surprising in South Africa, the U.K., Brazil, etc., we have different variants. Right now we have a lot of people being infected. And if we can cut that down with extensive vaccination, there'll be fewer variants emerging. And, flu vaccine uptake globally isn't very good. So we always have a lot of influenza, and that's why we have a lot of variation.
So if we can do something different with COVID, if we can get most people immunized and really cut down the number of infections, we can cut down the variation. And so maybe it won't be every year. Maybe it'll be every couple of years or maybe even every 5 years.
Now, the companies they're in the business of making vaccines, right? And so, unfortunately they're for-profit companies and that's part of their viewpoint. But I think you have to have a 10,000, 30,000 foot view and really look at this in the context of virus circulation. So I'm not sure it's a given -- you said 50-50. I don't know, it's hard to say. But I think right now, everyone's saying, "Oh, it's definite we're going to need a new vaccine because variants are turning up left and right."
But I do think once we cut down the circulation globally the variant emergence will be a lot less.
Makary: It seems like a new variant that has yet to mutate, a variant that could say be a concerning variant in the future, would probably not arise from the U.S. or Israel or the U.K. at this point, just because we're getting a fair amount of population. What country do you think is most likely to have a new variant emerge from?
Racaniello: That's a tough one. I mean, Africa, for example, is barely being immunized. Yet, South Africa, they had a variant emerge because they had a lot of infections. But in many other countries, in Africa, there's not a lot of circulation -- or maybe we just don't know it because we're not testing.
So I would say any country is at risk if they immunize a good fraction of their population. So right now Europe is not doing a good job immunizing and they have a lot of circulation. So it could just as well arise there. I mean, it could arise in a little pocket and in a state in the United States that decides it doesn't want to be vaccinated. So wherever people are not immune, that's where it's going to happen.
Makary: Where does influenza -- the strain that threatens the United States each year -- where does that typically come from?
Racaniello: So influenza is a seasonal disease that peaks in the winter in temperate climates. And so when we have our winter, we have our flu outbreak, and then we move into summer and then the flu season is in the Southern hemisphere. So those viruses down there are the ones that come to us for our next season. And so the surveillance that's done by WHO always uses the flu viruses circulating in the other hemisphere to try and get a handle on what we're going to have. So there are viruses in people, the year-to-year epidemic influenza viruses circulate in people, and it sets where we get them from.
Makary: Some have put out there that it's possible that vaccinated immunity, or maybe natural immunity, is lifelong against this novel coronavirus. Of course, with the disclaimer that we don't know, but it's a possibility. How much of a possibility is that?
Racaniello: So that statement is based on our understanding of the common cold coronaviruses. There are four different common cold coronaviruses that circulate globally. They infect most people on earth at one time or another. And we used to think that those viruses did not change. Now, a study is in pre-print form right now which shows that's not true. They change about every 8 years or so. So, you get infected with a common cold coronavirus, you get mild disease because you've got some kind of immunity. And then in 8 years, you get infected again, you never get really sick though.
So you have enough immunity to prevent disease, but not enough to prevent getting infection.
So if that holds true for this coronavirus, then it's hard to know. I mean, some people do think this will eventually be another common cold coronavirus. So you won't have lifelong immunity, but you will have enough so you won't get sick and you'll get infected every 8-10 years. And you won't even know it perhaps, and that'll give your immune system a boost and then you'll go on for the next 8 years.
So I think that's a likely scenario because the virus is changing and it's unlikely that it would be like, say measles, where a childhood infection or vaccination basically protects you for the rest of your life. I think that's unlikely for this virus.
Makary: And I saw that CDC report that there were about 5,000 infections out of roughly, I think it was 60 million people vaccinated. And it appeared that those were mild cases when they did occur. Is that right?
Racaniello: That's right, yes. They're mild. And that's going to happen because a fraction of the population, the vaccine efficacy is not 100%. So they're always going to be people who are infected. And they're also people who do not respond to vaccines. A small fraction of people don't respond to any vaccine. And so they can be infected.
But yes, the prevailing idea is that if you have some kind of immunity it will protect you against severe disease. You'll just get a mild or asymptomatic infection.