Many of the questions I’ve gotten recently surround vaccines and kids. Adolescents were approved last week and younger kids are a ways off, but probably in the late fall. It is clear, though, that there is going to be greater hesitancy about vaccinating children than adults. Some of this relates to ethics and global vaccine sharing but some simply relates to parents -- even those who eagerly vaccinated themselves and who generally vaccinate their kids -- seeing the risk-benefit tradeoff differently.
I’m sure I’ll write more than once about the decision-making piece of this over the next months, but I wanted to start with the science. For many people, I’d argue these choices would be easier given more information about the details of the science, where things are with the vaccine in kids and what kind of safety protocols are in place.
Rather than try to explain this piece myself, I thought I’d ask someone who knows more. A lot more. Amazingly, Stephane Bancel, the CEO of Moderna, agreed to walk me through these questions. Our interview is below (slightly condensed, but only slightly). Read to the end to find out a couple of other amazingly cool things that the mRNA technology might provide.
Most of what I want to talk about are vaccines and kids. But I wondered if you could start with a brief description of why the mRNA technology is different from the way we typically deliver vaccines, and maybe in what ways it is not different? [Editor note: read more on vaccine basics here]
The very first technology for vaccines, going back more than 100 years is to give people a small quantity of a virus. It's called a live attenuated virus, or a live attenuated vaccine. Basically, you give a very tiny bit of a virus, so you don't give the disease, but give enough of an exposure to the virus so the immune system makes antibodies. If you get the real virus later, you're going to be fine. So that was the old technology.
For the last 40 plus years, people have made one protein of a virus in a bacteria in a reactor using biotechnology. And then they will inject that protein in your body [and you make antibodies to it]. That was good.
But what mRNA does is it directly codes the protein of a virus into the mRNA message. We inject it into your body and your cells read the message. Your cells make a protein of a virus, exactly like if you had an infection, which is why the efficacy is so high.
That efficacy was surprising to everybody, but it didn't surprise us. Efficacy is so high because it's exactly human cells, not bacteria cells, making exactly 100% of a copy of a protein of a virus. Like if you had a natural infection, but we don't give you a virus. And because of all the investments within the technology, we can give you a high dose of mRNA. That makes a lot of copies of a protein, which is why your immune system gets so much exposure to it. It's a very strong response so, when you get a natural infection, you don't get sick.
Let’s turn to kids. The Moderna COVID-19 vaccine right now is approved under Emergency Use Authorization (EUA) for 18-plus. Two big questions we hear are, first, why would it be different in kids (or maybe it wouldn't be)? Second, why did you not put kids in the original trials?
The second one is the easiest. The regulators do not want us to start in kids -- this is true across the industry, it’s not an mRNA thing or a Moderna thing. Because vaccines are given to healthy people we do not want to start in kids because there is always a risk in clinical trials; zero risk doesn’t exist. And they don't want to do it until we show adults are very safe in a big study; and that it’s effective. Because you won't take a risk on a teen or child if it was not effective or not safe. I think it makes a lot of sense.
On the first question: we went in two phases which is typical in the industry. When you are okayed by the regulator to go down in age from adults it is usually to 12-plus. What the regulator thinks is that teenagers, because of how the immune system has matured, and because of their weight, are closer to adults. And so go with the same adult dose. They look more like an adult than they look like children from a virus standpoint.
Then when you go lower, because of the biology of young kids, you have to do two things. First, you have to go down in age slowly. So you don't go down to six months of age right away, you go down to, say, eight, and then to five and then you go into infant down to six months of age. And then, as you go down, you do not give a dose you give to teens or adults. You start at a lower dose. You try several doses, going up slowly, because you want to find the right spot where of course the product is safe, but it’s effective.
So you it's almost like you re-start at phase one of the adults, like what we did with Dr. Fauci back in March 2020. There, we started at 25 microgram, 100 microgram and 250 microgram. The dose that is now given in the US is 100 microgram, but we had to try because we didn’t know what was the right sweet-spot.
You have to do the same process with children because their immune system is different than a teen or an adult. And because the body weight is so much smaller, you don't want to overdose, of course. So you try different doses, as I describe, but you start at a lower dose, then the middle, then the high dose. And the high dose is the current adult dose. You see in children how they respond, and then you pick the dose that you ask the regulator to authorize.
When you say you're looking for efficacy, you're obviously not looking for phase three style efficacy, you're looking for antibody production...?
Right. It's very typical in vaccines, that once you have antibodies correlated to efficacy in adults you can do what is called an “immuno-bridge study” for teens and kids. You look at the level of antibody per volume of blood, and the regulator considers that at the same level of antibody that you saw in the adults, you will get the same efficacy. It is scientific logic.
Where is Moderna in terms of timing on adolescents and kids?
In the teens, we shared the data last week, showing the same safety profile as adults, and 96% efficacy. We are a couple weeks away from filing to FDA, because we need to put all the pieces together. I would expect early June filing. And then we expect the regulators to take a couple of weeks. So I would expect we should get the teens late June, early July. People can be vaccinated before getting back to school in September. So everybody can have a nice school year in middle school and high school.
In the younger children, we anticipate it's more late summer, early fall data, and then again a few weeks for approval. We have a goal to have most of the young children where parents want them to be vaccinated or their school wants them to be vaccinated by the end of the year.
That is a good segue into the question of how people think about this particularly for younger kids. The risk benefit trade-off feels very different. One piece of that is the question of safety. Can you start by talking about how you evaluate safety both before and after the EUA, and then we can talk about the broader picture?
The safety before EUA is based on studies of thousands of kids and teens. It's a big study. And as you know, in the adults, we have now more than 65 million adults with a vaccine, so it’s starting to be a very big database. The CDC, when they were looking into the J&J clotting issue, confirmed in written statements they had seen no blood clotting with either mRNA vaccine. This is a good sign for where things are going.
What we'll do if we get the EUA in the teens, and later in the kids, is do exactly the same protocol of safety follow up. Any reported event, by a healthcare professional or family, there's an 800 number, you can call the FDA or you can call the company. All those data aggregated and we talked to the regulator on an almost daily basis.
I think, for me, the J&J vaccine pause is the best example to the American public that we have an amazing FDA in this country. Out of abundance of caution, they said “There’s something funny, let's pause because if it's real, we're going to hurt people. It’s a vaccine: we cannot hurt people, it’s here to protect healthy people.”
People should be very comfortable that as those vaccine gets used at any age range from adult to teens to kids, there's an incredible follow up daily. Any signal of concern, we talk to the regulator right away, and like J&J did with the FDA we would rather pause for a few weeks out of caution, then take any risk to anybody.
I want to ask a question I get a lot: What if there is some long term bad effect that might happen in 10 years? What do you say when people ask you this?
Proving a negative in science is impossible. But it's highly, highly unlikely is what I believe. And why do I say that?
First, the mRNA molecule we inject has been proven by outside academic labs to be gone from your body in 48 hours, it's totally cut in pieces. mRNA is letters -- the four letters of life -- and those letters are cut in pieces. It starts at hour six, by 48 hours there is nothing left in your body. This is proven scientifically by outside labs, published, peer reviewed.
The second piece for safety is that it is proven, again by an outside lab from Georgia Tech, that the mRNA does not go into the nucleus, which is the envelope in the cell protecting your DNA. So the risk of the mRNA from the vaccine getting into your DNA and creating, let’s say, cancer or genetic disease down the road...we believe that risk doesn’t exist, because we have proven the mRNA doesn’t get close to the nucleus.
The third piece is around the lipid. The lipid is a ball of fat that is put around the mRNA to protect it from your blood until it gets inside your cells. That is a biodegradable piece of fat, and its half life is two hours. So basically it gets into your cell and it falls apart in pieces; by the time you get to five or six hours, it's all gone.
So is there a theoretical long term safety risk? There's always risk with anything we do. Including, you know, the lipstick you use or a cream you use.
My kid are teenagers. But if I had young children, I would definitely want them vaccinated.
The reason for this vaccination...there are a number of things to look at. The first is the variants. The variant of the virus we're seeing right now in India are also affecting children. So we should not be naïve that the old strain we saw in the US in 2020 is the same as the strain coming next year. You see what happened with the UK strain (B.1.1.7); it’s more contagious and is now the dominant strain in the US. We see the B.351 strain, or the P.1 in Brazil also have cases of teenagers and children being sick. You're seeing the same thing in India right now. Those are the next trends of we're going to get next winter. That’s just how viruses work.
The second thing to look at is the protection of a parents, the teachers in school and the elderly. Let’s say, children get infected in the winter by the B.351 variant from South Africa, they might get no disease, because of the immune system. Or they might just be tired for a day, but you will not notice as a parent that they had.
But they might give it to the teacher and our parents and our grandparents. And that's what the risk happens, because those people would have been vaccinated a long time ago, possibly with waning immunity. And if you have a variant, the efficacy of a vaccine will be lower.
Third: vaccination for me is really about protecting the individual because you never know how somebody might react to a virus. They might have another comorbidity factor that you don't know. Sometimes kids have comorbidities that parents don't know. So we should not assume that the kids because they look healthier from outside that they're healthy inside.
I think the tension in messaging is that, on the one hand, we want to be sending the message that the vaccines do provide some protection against variants. Sometimes you hear, “Why would I get vaccinated because it won’t work against variants?” Actually, it does work, just not quite as well. That’s why we need so much of the vaccine. But we need to thread the message in a way that is difficult.
Let me ask you one more thing in this space. My kids are six and 10. They're not yet quite eligible for the vaccine yet, but I know when they are I am going to get the questions from people: “Should I vaccinate my kids and why?” So, what are the two sentences for me to tell them?
First: I want protect my kids, in case perhaps they have a comorbidity that we might be aware of so they could get really sick. Second: to do our job as a family. Because if the FDA has approved a vaccine, it’s safe.
And I want to do my part as part of my family to protect the community. The teachers, our friends, our friend’s parents, ourselves as parents, the general community. People should not forget this thing spread like wildfire. The impact of just one person could be 10 people hospitalized in the next three weeks, or four weeks, because spread is exponential.
Last thing! I know you were working on a lot of stuff prior to this which was not COVID. What is the most exciting next virus that you're fixing?
So there are two that I will draw to your attention. One is the flu. As you know, the flu kills 30,000 to 60,000 Americans a year, depending on how bad the strain mutation is. Efficacy of the flu vaccine is 60% in a good year, in a bad year 25 to 30%. We believe with the mRNA, because of the speed at which we can follow up a variant of flu (“seasonal strains” they are called, but it’s the same thing as a variant) we can get the world 90 to 95% efficacy flu vaccine.
And our next exciting thing, which is going to be in the clinic very soon, is to do a study for flu. This will go very fast because flu is a very well known virus. Our goal is to combine in a single dose a variant boost of COVID and a variant boost of flu. In a single dose, you get at your CVS or primary care doctor every year, and you have a great winter with no flu, no COVID, and you're a happy lady.
The next one is CMV. It's a very poorly known virus. Cytomegalovirus is the number one cause of birth defects in this country and many countries in the world: 1 in 200 kids. The industry has tried for 20 years to make a CMV vaccine. They all failed, because it is a very complex virus. We have a vaccine that is going into phase three as we speak: Six mRNA molecules in each vial to make six different proteins, because it is such a complex virus. The data so far looks beautiful.
What we hope is to get this to the finish line in a few years. The study will take a few years to enroll and to wait for natural infection like in any vaccine study. But what I'm hoping for is we're going to get a high efficacy vaccine, which we're all thinking will happen because of the science. Then women 16-plus before getting pregnant get vaccinated, so that if they get infected during their pregnancy, they won’t transmit to their baby and they will not have babies with birth defects.
I'm so passionate about this one. You know, I really believe every woman should get that option to get that vaccine. You know, I have two young girls -- 18 and 17. And I really want the vaccine to be launched soon because I really want them to get it before they get pregnant.
This is awesome. I write a lot about pregnancy and CMV is something that comes up often, with women coming to me and saying they were affected but had never even heard of this before, despite how common it is.
It’s really sad, because what happens is OBGYNs do not talk about it, because there's no vaccine. And as you know, couples and expecting mothers are already freaking out about everything else…
...Yes, pretty much my whole career is built on that fact...
... And all of us want to protect our offspring, this is just nature. And so we’ve kind of decided not to talk about it, because you can do nothing. What what we're trying to do, with a great partnership with the CMV Foundation is to drive the awareness in the next few years. So that when the vaccine gets authorized or approved, but people are aware so they can make an informed decision.
Keep the thoughts coming. I don’t always write back, but I read everything.
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