Dr Muller and Dr Offit discuss COVID-19 variants and their effect on vaccine development.
William J. Muller, MD, PhD: It’s worth talking about variants, because this is a bit of the discussion at the review committee meeting for the FDA [Food and Drug Administration]. It has 2 components to it. One is, do we expect this will be a 3-dose vaccine for everyone in the future? I think the authorization will be for a 2-dose vaccine from Moderna and 3 doses from Pfizer. But everyone is expecting an eventual third dose from Moderna. They intentionally use the term third dose because we are throwing around the term booster doses if there’s no need for a third dose. Do you have any thoughts about that, and do you think we need to message that a little better to parents and the public?
Paul A Offit, MD: This is a 3-dose vaccine. Moderna is going to launch a 2-dose vaccine for children younger than 5 years. It’ll probably be available as early as next week, and today is June 16th. By June 20 or 21, it could be available for children younger than 5 years. It launched as a 2-dose vaccine, but the point that several committee members made during these past 2 days is not to think of this as a 2-dose vaccine with the third dose as a booster. This should be a 3-dose primary vaccine if we’re going to get the kind of protection we need against these subvariants. In other words, the primary series is 3 doses, and boost is the wrong word. Because the way that the CDC [Centers for Disease Control and Prevention] defines this is that you’re fully vaccinated with 2 doses, but you’re up-to-date with a third dose. That is wrong. This is a 3-dose primary series for your children. Pfizer’s vaccine for children younger than 5 years is currently a 3-dose vaccine, but I know that Moderna is doing studies with 3 doses, and they should have those studies available, according to them, by July. Thus, I think very soon we’ll have that third dose, which would be given months after the second dose.
William J. Muller, MD, PhD: The next question that a lot of people are raising is whether the third doses that might be given in the coming months would be specifically directed at variants. Moderna had some data last week in adults that suggests, at least in antibody studies, that the neutralizing capacity from people who received a variant vaccine was better than whether they received an extra dose of the vaccine based on the initial strain of the virus.
Paul A Offit, MD: That’s an important point. On June 28th, the vaccine advisory committee will be meeting to discuss that issue: Should you give a very specific vaccine in the fall? The so-called bivalent vaccine, where one of the mRNA components is against the ancestral strain, and the other one is for Omicron. There’s a lot of evidence why that wouldn’t be a value. I know this is a contrary point of view, but here’s what I would say. The good news about the ancestral vaccine is that a third dose clearly increases your antibodies against the Omicron subvariant, as was shown by Pfizer in the data presented yesterday for the child younger than 5 years. With 2 doses, they didn’t have neutralizing antibodies against Omicron. With that third dose they did, and that’s the good news about this ancestral vaccine. If you give 2 doses of the ancestral vaccine and a third dose with the ancestral compared with 2 doses of the ancestral vaccine and a third dose with the Omicron vaccine, is it better to have Omicron as your third dose in a person who is seropositive? Because a large percentage of this country is seropositive. Thus, if you’re only looking at people who are seronegative, you’re talking about a very small percentage of people in this country who have already been naturally infected, immunized, or both. You’re probably talking at least 80% to 90% for people who are already seropositive. And when you look at those data in the person who is seropositive, there’s not much difference. Also, in the nonhuman primate studies, when they give 3 doses of the ancestral vaccine or 2 doses of the ancestral vaccine and then the Omicron booster…there is no difference. Unless there are data contrary to those data, I don’t see the point of doing the Omicron-specific vaccine. I may be in the minority here. But if we’re going to follow the science, we need to clearly show the science proves that.
William J. Muller, MD, PhD: I don’t disagree with you. I was going in that direction, because one of the questions that a lot of providers are going to get from parents who are about to start vaccinating their children is, “Should I wait until the fall and get the primary series of a variant vaccine?” And from what you’re saying and from what I understand of the data, it makes more sense to get vaccinated sooner than it does to wait for a specific vaccine, because your protection is likely to be similar, at least against severe disease, which is the goal, whether or not you get antibody levels that are significantly higher in neutralization capacity. And an in vitro study doesn’t necessarily tell you whether you get protection from disease, and the 2 do correlate to some extent. But if I have 5 times the level I need for protection of disease vs twice the level I need for protection of disease, it may not matter. I want to get twice the level sooner.
Paul A. Offit, MD: That is exactly right. If you look at the people who are seropositive who get the Omicron booster or the booster for the ancestral strain, the Omicron is about 1.7-fold higher, which although statistically significant, is unlikely to be clinically significant and will no doubt be short lived. It’s probably not associated with an increase in memory B cells or T cells. If those are the best data to show, then it’s hard to embrace a more expensive strategy.
William J. Muller, MD, PhD: I think that’s an important point for the providers who are listening to us to understand.
Transcript Edited for Clarity