Dr Muller and Dr Offit discuss recent developments in the COVID-19 vaccine for children younger than 5 years.
William J. Muller, MD, PhD: Were there any other data from the review committee panel about safety and efficacy that were notable in children younger than 5 years relative to other age groups?
Paul A. Offit, MD: There was a difference in terms of efficacy to some extent. Typically, the Pfizer and Moderna vaccines, when given as 2-dose vaccines, have tracked right next to each other. It was true for adults, it was true for children aged 12 to 17 years, and it has been true for children aged 6 to 11 years. But for children younger than 5 years, there was clearly evidence of at least some protection. It depends on which subgroup you’re looking at. Somewhere between 37% and 50% protection against mild disease, which I think will predict even better protection against severe disease. After 2 doses with the Pfizer vaccine, you didn’t see evidence of protection, so you can’t assume there would have been “… against mild disease,” because all they were seeing was mild disease. Thus, without evidence of protection against mild disease, it’s hard to assume there is going to be protection against severe disease, and hence Pfizer decided to make it a 3-dose vaccine. Moderna will also be a 3-dose vaccine, but you could argue that from the time of your first dose, where there will be protection within 6 weeks, that may not be true for Pfizer’s vaccine until 14 weeks. But I want to offer the caveat; let’s see what happens when the vaccine gets out there. And we’ll see what the real-world efficacy is after 2 doses for both vaccines, because right now the numbers are small in terms of participants that had mild disease during these efficacy studies. But that was a difference.
William J. Muller, MD, PhD: That’s an interesting point, because I’ve been asked by people whether there is a preference for one vs the other in terms of what you give your child. I think our data in other age groups have suggested there’s not a significant clinical difference in outcomes based on which platform you were vaccinated with. I would not expect that to be the case in younger children as well, even though the data suggest that 2 doses of the Pfizer vaccine are not sufficient for significant protection, and a third dose is necessary. But because both vaccines will likely become 3-dose series, it may make a difference which one you get first. Are there any other expectations about authorization that might be worth delving into? Everyone is expecting both these vaccines will be authorized for use in the youngest age group in the future. But it’s also important to emphasize that there are going to be ongoing studies of real-world efficacy in these age groups. Are there any other developments we would expect in terms of the delivery of the vaccine? I think the timing is a little different for some of these. Are we going to try to rationalize this? Do you think in the future that doses will be given on a regular schedule, regardless of the platform?
Paul A. Offit, MD: The critical question moving forward is, when is it going to be best to vaccinate? And that’s going to depend on immunological memory: How long does memory last? I think we’re going to learn that over time. Also, it’s going to depend on how the variants change. There may be, and it hasn’t happened yet, a variant that arises that is resistant to protection against severe disease, in which case we are starting all over. Thus, I think the critical question is, how long does memory last? If memory is long lived, then the earlier we vaccinate, the better. If memory is shorter lived, then maybe you want to delay it until a time when people are more likely to be hospitalized or die from this disease. But I think we’re going to learn as we go, and there will be better vaccines. I think there will be safer vaccines. You know that the mRNA vaccines are rare causes of myocarditis: inflammation of the heart muscle. You also know that the Novavax vaccine appears to be a rare cause of myocarditis as well. Novavax vaccines are purified protein vaccines, which were a different strategy.
To date, it looks like the AstraZeneca vaccine, which is a viral vector vaccine, doesn’t cause myocarditis, which is interesting. There was a publication in 2020 that showed molecular mimicry between the SARS-CoV-2 spike protein and the ɑ-myosin heavy chain on heart muscle cells, and you would have thought this would be a class effect. That anything that induces antibodies against the SARS-CoV-2 spike protein intuiting the disease would cause myocarditis, but it looks like from the AstraZeneca data that it may not be a class effect, in which case, it may have something to do with the way the proteins are processed or presented based on whether you give a viral vector vaccine mRNA vaccine, or purified protein. There’s a lot of knowledge to be gained there, because the history of vaccine development is always that over time you make safer, better vaccines. Thus, I think we’re going to have plenty of time to figure that out. This virus is going to be with us for decades, and that’s what you’ll see. There will probably be a nasal spray vaccine in the future, which may be better in terms of inducing local immunity and decreasing shedding to some extent. It’ll be interesting to learn more about the whole inactivated viral vaccine that’s being used in China, as well as the receptor-binding domain vaccine that’s being used in India other Asian countries, because that’s just part of the protein. Will that vaccine cause myocarditis, or are you missing a critical part of that protein? Hence, there is much to learn, and we’ve got to keep our eyes open and keep learning.
William J. Muller, MD, PhD: I know this has been a little controversial, but there’s been some discussion about whether delaying that second dose for some period of time decreases the risk of myocarditis. It seems to me, from a wider lens, that if we’re talking about affinity maturation and stronger affinity of antibodies and potentially diverse T-cell responses, that it’s really that third dose on top of at least the first dose that does that more than anything else. I wonder whether in the future a 2-dose vaccine series separated by a few months is going to be just as good.
Paul A. Offit, MD: Myocarditis is a generally male phenomenon, a young male phenomenon specifically, generally within 3 or 4 days of the second dose. I think in terms of spacing, there’s certainly data from Canada that suggests that spacing does make a difference. Again, we’ll learn as we go.
Transcript Edited for Clarity