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.
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.
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.
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.
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.
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.
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.
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.
Emily:
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?