Opinion | Is the Bivalent Booster Any Better Than the Original?

In this video, Jeremy Faust, MD, editor-in-chief of MedPage Today, discusses his recent article diving into new studies on the effectiveness of the COVID-19 bivalent booster versus the monovalent booster.

The following is a transcript of his remarks:

One thing that people are really interested in right now is this question as to whether the bivalent booster is better than what we had before.

Certainly, it was marketed as we have these mRNA vaccines, we can swap out very easily what’s in that vaccine, and make changes and keep up. And therefore, this fall, the FDA rolled out the bivalent booster, which had some of the original Wuhan spike protein recipe and some of Omicron; that’s the “bivalent” part.

What we now are looking at is laboratory data of people who got boosted either with the monovalent or the bivalent, and what we’re seeing here is that the monovalent works, the bivalent works, in terms of antibody responses, and the bivalent may work better, but if it does, it’s not by very much.

You’ve got really two kinds of studies: some studies that showed really no difference between the bivalent booster and the monovalent booster in terms of antibody levels, and then you have some studies that are suggesting that the bivalent booster did better and has a higher antibody response.

The problem with the studies that show an increase — that the bivalent is better than monovalent — really comes down to a couple of things. The first thing is that the increase isn’t that much. It’s not a 10-fold or 100- or even 1,000- or 10,000-fold difference, which we could expect to see. It was literally to the tune of a doubling or so, which is really not that impressive when you’ve swapped out entire parts of the vaccine in order to make a change. We were hoping for much more. We don’t even think that’s a clinically relevant finding.

The two studies that came out in the New England Journal of Medicine last week didn’t really find much in the way of any increase at all. There’s really these two kinds of studies: there’s the study that says there’s really no difference, and then there’s the kind of study that says, “Well, there’s some difference, but it’s very small.”

It turns out there were people who thought the differences came down to what kind of assays and tests were being done. It doesn’t seem like it comes down to the assay, and the reason that I think that is, is the most rose-colored-glasses-view study, the one that showed the biggest impact for bivalent over monovalent, came out of a pseudovirus study. Also, pseudovirus was the platform for the studies that showed no difference, and then live virus had some small changes.

So, really, it doesn’t seem to come down to the virus or assay that’s chosen. All the scientists that I’ve spoken to, including the authors of the studies, David Ho, Dan Barouch, and others have said that pseudovirus and live virus are pretty interchangeable, so we don’t have to worry that the differences are due to the platform.

It seems like the big difference comes down to timing, that people who got the bivalent boosters in the studies that made the bivalent booster look good had a different amount of time compared to the monovalent groups. In other words, the interval between when people had their last dose and when they got their most recent dose was different across the groups, making it more likely that the people who were in the bivalent side of these studies would be expected to have a higher response. That doesn’t prove the bivalent is better, that just proves that the timing was better.

So, there’s been this sort of online and siloed debate about whether the booster is a bust or whether it’s really better. You really have two sides, you’ve got the Paul Offit side with the New England Journal of Medicine perspective saying that the bivalent booster story is a cautionary tale. It’s not that it doesn’t work, it’s that we went to all this great effort and it might not even be that much better.

In fact, keeping any part of the Wuhan virus in the new bivalent booster might be bad, because our immune systems have seen the Wuhan strain so many times and that’s not even around anymore. We have Omicron and we have Omicron subvariants. We don’t want to be in a situation in which our immune systems are imprinted for Wuhan and then when they see Omicron, they shrug it off as nothing it needs to worry about.

On the other hand, you’ve got Team Topol, Eric Topol’s folks, who are saying that the bivalent is clearly better because of how well it did in these assays — look how important it is, look at the Israeli data. I think that those arguments don’t hold up.

But what I think is important though, and what I think Dr. Topol has right, is that there is a group of people, high-risk people in particular, who need to stay up-to-date with their boosters. Whether it’s bivalent or monovalent, it doesn’t matter, because we don’t want to discourage those people who need it the most from getting boosted going forward.

I think a monovalent, Omicron-only booster is probably going to be the better choice, but we’re waiting for the FDA and for Pfizer and Moderna to announce where they’re headed. I hope that’s what they do.

If you have questions or comments, please leave them below. Thanks for joining us.