What’s Surprising Scientists About the Omicron Variant

BIANNA GOLODRYGA: Well, now, as at least 57 countries confirm cases of the Omicron variant, questions surrounding the latest strain do remain unanswered. Moderna chairman and co-founder, Noubar Afeyan, is at the forefront of research and scientific development in the fight against COVID. He joins Walter Isaacson to discuss Omicron and the future of vaccines.

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WALTER ISAACSON: Thank you, Bianna. And, Noubar Afeyan, welcome back to the show.

NOUBAR AFEYAN, CO-FOUNDER AND CHAIRMAN, MODERNA: Great to be here, Walter.

ISAACSON: We’ve seen with the new variant, the Omicron variant, that sometimes here in the United States 3/4s of the people who have been infected have already been vaccinated. One-third of them have had booster shots. Should we worry about the effectiveness of the vaccines?

AFEYAN: Well, Walter, when news of this virus variant first appeared, the scientific concern had to do with just the sheer number of mutations. And there has been a concern, pending data, that it may, in fact, evade some of the immune response we can generate. And so, we are waiting for the data to confirm that. And data is just beginning to trickle it. And it seems to suggest that indeed there is some diminution in the degree of defense, if you will, with the vaccines. But with a booster, it seems that it could be sufficient. And we’re waiting for a lot more data before we could say that definitively. And so, we’re really in this waiting period for a few more days before we’ve got data. The problem with such a new threat, as we saw two years ago with the actual original strain, is that it’s easier to make pronouncement either in the worrisome direction or in the overconfidence direction. And one thing we know is that both tend to be wrong. The data eventually clarifies things. And so, our position is, let’s get the data and then act swiftly to protect as much as we can everybody.

ISAACSON: But now, that we’re going into the holiday season, what do you say to people? Should they get a booster shot right now before traveling home?

AFEYAN: All the evidence, Walter, suggests that even against the Delta, before we get even to Omicron, a booster would be important for people who are six months away from their second dose. And the — and so, I really want people to understand that it’s Omicron that should cause them to get a booster. The Delta variant is a serious threat in itself for reinfection. Lots of data has come out suggesting that in certain vaccines, particularly, the effectiveness goes down precipitously after a few months, and that the booster is the way by which we can get it increased again. And it’s all, Walter, about the measurement of antibodies that are increasingly being done to show that if you don’t have a sufficiently high level of antibodies, your first line of defense to protect against infection, not the degree of seriousness but just the protect against the virus getting in, is now down. And I think that is an important part of the story that’s emerging, where I think we’re having to do a lot more antibody-based testing to begin to see who is more or less vulnerable and who we should think about boosting. But for now, everybody who is eligible for boosting, in my view, all the data suggests should be boosted against Delta, and then that’s the best defense we have against Omicron for the time being.

ISAACSON: So, let me get this straight. You’re saying that maybe people like myself, if we can, should get an antibody test?

AFEYAN: I believe, in general — I’m not setting policy, but I do believe that we have completely underutilized the amount of information that antibody levels and measurements can give us. This is not an antibody against the virus. This is not antibody against the antigen. This is antibody against the vaccine. In other words, a vaccine generated antibody. And the level of that is what all the data that’s coming out seems to be correlating with effectiveness of the vaccine. So, if you have, say, a thousand units of antibody, you seem to be extremely well protected, then you watch as that comes down to 100 or 50 and you’re vulnerable. So, we already have some sense of that. Now, there isn’t a clear diagnostic test that says above 100 you have this below — but just because we don’t, it doesn’t mean as a general population matter, we should not be looking, just like looking at viral sequences, we should be looking at antibody levels because there is just too much variation going on. The virus is changing. Our immune response is changing. It’s also waning. And the complexity there can only be counteracted by information, repeatable experiments and then, making judgments on facts.

ISAACSON: So, you think that the government should authorize and doctors should give you antibody tests to see how well the vaccine has kicked up your immunity?

AFEYAN: I believe that that is a serious topic that the regulators should take up because of the fact that it is an important piece of information that they are using to authorize boosters, to authorize vaccines. And yet, somehow citizens do not have access to this information. So, yes, I believe so. I say that as an innovator, as a technologist and as somebody concerned about making science-based decisions. But, look, Walter, the reality is if the audience is say, why isn’t this being done, it sounds reasonable. The answer is because we are living at a time which comes after a historic vaccine industry and in a public health segment that has done things a certain way. And measuring antibody levels for vaccinated people has never been something that has been deemed necessary or even useful. However, this pandemic afflicting hundreds of millions of people, 5 million plus dead, I think has to cause us to say, what do we do in 2021, 2022, now what did we do 10, 20, 30 years ago based on the threat we felt there? So, yes. My clear answer to you is, I think that should be given strong consideration. And, in fact, in the U.K., it is being done. The government is mandating certainly for a certain vulnerable population antibody-based testing. I think we need to look at that here.

ISAACSON: You have probably seen, of course, your counterparts at Pfizer have said that their booster shot really does kick up the antibody levels. Is there any reason that the Moderna shot would be less effective?

AFEYAN: I don’t know of any reason for that. And in fact, there is no question that the boosters that we administer and that they administer kick up antibody levels. Whether the antibody levels are sufficient to protect against Omicron, we have very preliminary data that I saw yesterday from the Pfizer group. We need to wait for more data because that — though some of those assays need to be done in a way that represents the real-world effectiveness and antibody levels and connecting to that requires quite a bit of work. And so, my sense is the beginning sense of data, which is optimistic, will continue and we will follow up with a much more set of robust findings. But, yes, I expect our vaccine, because it’s essentially the underlying mRNA technology of Moderna pioneered over the last 10 years is what’s being used. And so, I don’t see any mechanistic difference between the two.

ISAACSON: The mRNA vaccines that Moderna pioneered make it so that you can just code to a molecule, how to do a spike protein facsimile, right, that will protect against the virus. Are you working on a new variant of the vaccine that specifically targets the mutated versions like Omicron?

AFEYAN: Yes, we are. And in fact, we started right at Thanksgiving with that chase. Because as soon as we found out about the sequence of in new variant, we could see on our computer screens instantly the 30, 35 changes that have happened in that spike protein and the 10 or 12 highly concerning ones in the most important binding region of the spike protein. And it was fairly unprecedented, and I must say surprising. I mean, scientists are professionally trained not to be surprised. But it nevertheless is surprising because of the extent of the variation. So, yes, we instantly have started to apply our technology like we did back in January of 2020 to computationally design and begin to make these constructs. And we’ve said that we think within a two to three-month period we will be way down the path to be able to supply, if that’s absolutely needed. But I’ll also say, Walter, that the — in the meantime, we do not only have our original 1273, it’s called spike vax now, vaccine. but we also made a multiantigen vaccine that includes sequence against the Beta variant. So, we have data on that in human that shows strong effectiveness against the Beta and the original. We have another double vaccine against the Delta variant that is being tested in humans as we speak. So, we’re not going from the original strain all the way to Omicron. We already have a Beta combination, a Delta combination. And in our data, we are very eager to see if the Beta or the Delta already gets us more protection towards Omicron than the original strain. Some of us suspected that might be the case. We’ll wait to see the data. So, this is a — you know, the beauty of a code-based approach as you and I talked about in the past, is that you should be absolutely adapting as the virus is adapting so that you stay — try to stay close or ahead of it. And that’s exactly what we’ve been doing.

ISAACSON: You said that you were surprised when you looked into computer screens and you saw all of the mutations, all of the variation. Tell me, what does that show about this virus, this underlying coronavirus?

AFEYAN: Well, I mean, I think that we are in uncharted territory. You know, when we spoke a couple of — a year ago, I had mentioned that this unprecedented because of the degree of social interconnectedness that humans have, that this experiment of the pathogen that is preying on our social nature is gaining such a foothold because we are so interconnected. That was unprecedented. Now, that unprecedentedness is manifesting in the ability for the virus to adapt by getting into so many hosting that it infects. Plus, now, we are learning a vast number of animals, deer, other types of animals, that also are carrying the virus, each of those might as well be a biotechnology lab running an experiment of how to defeat their immune system. So, you have millions of experiments running against the vaccine that is trying to escape the immune detection. And add to that the interesting scientific complexity of an immunocompromised patient in which the vaccine can persist, unfortunately. But in so doing, can run the experiment for months and months and months. You take all that together and the nature of evolution as such that if there is a solution to be found, with enough parallelism, enough time, it will find it. And that’s what we’re up against. The degree of change we have seen before ends up being limited by the expanse of the experiment that’s being done. Now, that that seems to be quite a bit more expanded, we will not be as surprised to see these things. But it does concern us that if you have this strain, the question is how many other strains and how many other experiments are there? And how do we continuously stay vigilant? And this is the key thing, I think, Walter, that we are all exhausted, those of us working on vaccines, those of us providing health care but also, in general society from this topic. On the other hand, the virus really doesn’t have exhaustion as one of its features. And so, we’re going to have to stay super vigilant. And I can’t, as we sit here to tell you, this is a one-week battle, a one-month battle, a one-year battle or longer battle. And I know people don’t want to hear that. But at least the defense of our health requires us to assume it’s a longer battle and hopefully be wrong.

ISAACSON: You talk about the challenge of unvaccinated people around the world. Do you think that Moderna and other drug companies should be doing more in terms of sharing intellectual property or finding ways that this can be done cheaply enough and widely spread enough?

AFEYAN: Walter, everybody should be doing the most they can. And I think everybody is doing the most they can. The way of doing it, people can disagree on. And it so happens that the people developing and making the vaccine have both the knowledge and the responsibility to judge what is the most effective way to do that. We have increased our supplies from being able to make dozens of doses a week before this to hundred million plus doses per month going up to 200 million doses a month next year or more. So, the volume has expanded drastically, in hour hands, through partnering of ours, as well as other companies. We have announced that we will set up a factory, for example, on the Continent of Africa, which will happen over the next two to three years. And people say, oh, well, that’s too late. Well, the reality is that’s too late if you assume it’s going away in a few months. But having vaccine security by having a plant operating in a location I think is an important midterm response to this. Importantly, last October, Moderna was the first and sadly the only company who came out and voluntary pledged not to enforce its intellectual property during the pandemic for anybody using mRNA to make a vaccine against COVID- 19. That has already enabled people making mRNA vaccines based on the 10 years we’ve done in this field to be able to offer solutions. People say to us, well, why don’t you give away your recipe? Why don’t you train people to make it? If we thought that that would cause more volume of production than what we’re already doing based on the network we have set up, we would consider it. But we said publicly, that’s simply is not going to be the case. There is nobody that will stand up manufacturing over an unprecedented molecule faster than we can, faster than we have and produce it at a quality. Keep in mind, Walter, they are going to be making a vaccine that we developed and we are responsible for the highest possible quality we can deliver. So, for all those reasons, despite the well-intentioned suggestions and attacks, I just feel like we’re doing what we can. We’ll do more as soon as it’s possible. But for the time being, we think we’re on the right course.

ISAACSON: Because of the Omicron threat, there’s been a surge of people getting vaccinated. There are now 200 million people — we just passed that mark in the United States. But that’s only 60 percent of the population. Is that a good number or are we really lagging behind?

AFEYAN: I think if you look backwards, it’s a great number. But compared to where we need to be to really protect the population, we’re lagging behind. And I think — I would invite people to think of it this way. It’s not a choice between getting a vaccine and not getting a vaccine. It’s a choice between getting a vaccine and eventually getting infected. And I think that people have to put on the balance the consequences of getting infected, which people might be underestimating by saying, well, it’s like a flu. I’ll get well. I’m not in that age group, I’m not worried. But the reality is that we don’t know much about in disease. And what we do know about COVID-19 seems to be leaving long-term effects in a significant proportion, 10 percent, 15 percent of people that we’re just beginning to learn about. So, I think given the choice between getting infected and getting the vaccine, the vaccine is definitely a much safer way to go. But unfortunately, people seem to be thinking only vaccine or no vaccine as though they are somehow impervious. And as you get Omicron, as you get other variants, it’s just a matter of time. The second thing I think it’s important to understand is, do we want, by being unvaccinated, to give ourselves the right to infect other people, especially loved ones? And there are many rights that we do not have in society, specifically as it relates to impacting other people’s lives. Whether it’s smoke, whether it’s the way we drive, whether it’s whether we can harm people physically, there are certain things that prevent us from doing things to other people. Well, it is clearly the case that getting infected, however safe you might feel from that, is a threat to the people around you. And I think for all those reasons, the responsible thing to do is to be vaccinated and the safety profile is such that the public authorities, the regulatory authorities have said on balance this is a far more protective measure than a safety concern. The virus is not. The virus would never get regulatory approval. It is far more toxic than it is helpful just because it helps our immune system wake up. So, I think that’s the balance that has to be struck.

ISAACSON: Dr. Noubar Afeyan, once again, thank you for joining us.

AFEYAN: Thank you for having me, Walter.

GOLODRYGA: An appeal there from the chairman of Moderna for everyone to get vaccinated. And finally, finders really are keepers. Even if it’s eight years late. Listen to this. These precious stones were discovered by a climber back in 2013. Now, he stumbled across them while mountain climbing on Montblanc. But he dutifully handed in the valuable emeralds, rubies and sapphires to the authorities. Well, now rewarded for his honesty the local counsel allowing him to keep half of the trove worth $168,000. The other half will be displayed in the Chamonix Crystal Museum. It’s thought that the jewels were on a plane that crashed on Montblanc in 1966. So, an early Christmas gift for that French climber for his honesty. Honesty does seem to pay off. Great story there. Well, that’s it for now. Thank you so much for watching and goodbye from New York.