Key Considerations for Vaccination and Boosting Amid COVID-19 Variants

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Key opinion leaders share insights regarding considerations for COVID-19 boosters amid variants.

Mitchel Rothholz, RPh, MBA: Let’s discuss the new booster vaccine, why it’s being recommended, and the importance of it. We’ve moved from a monovalent to a bivalent [vaccine] that covers the original vaccine strain as well as the new Omicron BA.4 and BA.5 strains. As we’ve done this, there have been a lot of discussions. Even as the ACIP [Advisory Committee on Immunization Practices] and the FDA came up with their recommendations, several key factors were brought into that discussion. Let’s delve a little into that and why it’s so important for these boosters and why the recommendation came out the way it is.

Jeff, [let’s talk about] the differences between the new bivalent booster vaccine and the previous, which is still in the market. I want to make sure the audience knows that there’s still a population that gets the monovalent vaccine. Give us a little insight in terms of what the thinking was behind the bivalent vs the monovalent vaccine and [the reason for] that recommendation. You’re a liaison member of the ACIP. Give some insight for our audience of some of the key points that were discussed [at the ACIP meeting].

Jeff Goad, PharmD, MPH: The challenge that we have with COVID-19 is that we’re playing catch-up. For example, there was always a thought that we were going to have to modify the vaccine to keep up with the variants. But the challenge is the variants are moving faster than the studies. For example, the original bivalents looked at BA.1. Some looked at a monovalent.

Ultimately, after looking at some of the studies that look at the geometric immune titers—the BA.4 and BA.5 strains weren’t clinically tested on people because they were focusing on BA.1, and it suddenly changed to BA.4 and BA.5 as that got a foothold and took over within the world—we learned about the robustness of the immune system. With the ancestral strain, in the mRNA [messenger RNA], they were able to combine the BA.4 and BA.5 mutations into 1 antigen so that you have a bivalent with 2 antigens that are able to elicit a broad range of antibodies. That’s our strategy going forward, because there’s no way we’ll be able to stay ahead of the variants.

Within influenza, we get an early warning system from the southern hemisphere to help predict what might be coming our way in the northern hemisphere, but it’s always a prediction, and it isn’t always right. We don’t even have that for COVID-19 because we don’t have a seasonality associated yet. We don’t have a geographic region to watch to see what’s coming our way. We tend to look at Europe, but that isn’t seasonality—that’s travel, people going back and forth. Until we get an early warning system, we’re probably always going to be behind in the way that we create our booster doses for COVID-19. But having [boosters for] a broader range of some of the variants allows your body to develop a broader range of antibodies.

For a while, people talked about something called original sin, which in immunologic terms is an imprinting. That first one you got—for example, the [ancestral] strain—might be the only one to which your body can respond with antibodies. So far, that has been proven wrong with COVID-19. We don’t see that. We see a more adaptive immune response. We see a broad array of antibodies being developed. We hope that this bivalent is able to kick in that immune system. Whether you’ve had the disease or had the vaccine before, it can create a hybrid immunity in those who have had the disease and boost the immunity, even just to the monovalent, so that with the next variants coming out, hopefully this vaccine will elicit a broad enough array of antibodies to protect us. But the real question is for how long.

Mitchel Rothholz, RPh, MBA: The approach we’re seeing with COVID-19 is similar to what we see with influenza. You try to get a component in the vaccine that’s going to be close enough to cover several of the variants. That’s where we are. Things may change, but hopefully there are close enough similarities to get the response needed to protect against those variants. In the news reports around the world, we’re seeing other variants being identified. Is that a concern? Or should we work with what we’ve got and monitor?

Jeff Goad, PharmD, MPH: Our surveillance system is very robust. We have variants of interest and variants of concern. We wish that some of the developing countries had better surveillance systems, because data are only as good as how reliable they are. If you aren’t getting good data, then you aren’t able to make good predictions. Our data systems in Europe and in the northern hemisphere are pretty robust, so we should pay attention to what new variant is beginning to emerge and watch its patterns.

Now that we understand patterns of how they spread—how BA.4 came out, how BA.5 took over, how Omicron began to edge out its competition—we know how this virus works. It’s evolution in action. Instead of millions of years, we’re seeing it in months. These RNA viruses make so many mistakes when they’re replicating that you can see these variants emerge very quickly, but they need populations to take hold. The bottom-line message is that COVID-19 isn’t all about the United States. It’s about getting the global community to vaccinate, surveil, and use masks when rates go up. It’s doing all these things globally that will eventually help us in the United States. We can’t build a wall. We learned that early on. You can’t keep COVID-19 out with a wall. It’s coming in. It’s a global problem that we have.

Mitchel Rothholz, RPh, MBA: Another way I’ve heard it described was to reduce the reservoirs for the viruses. That’s an important point to remember. There’s 1 question that a lot of providers get asked, especially with these new boosters: “Is this the only vaccine I’m going to need to get now? Or am I going to have to get another vaccine every couple of months?” How do you answer that?

Jeff Goad, PharmD, MPH: My crystal ball is a little foggy, but it looks like we’re probably going to have a series of booster doses depending on which variants come out. I’d rather we get to a once-a-year booster. People are hoping that we’ll get to that so that you aren’t getting one every 2 months, but it’s hard to say where we’re going. We’ll see what this booster dose does. We’ll see whether we have a winter surge and how it holds up, and we’ll keep surveilling to make sure the vaccine is still keeping people out of the hospital and keeping people from dying.

Transcript edited for clarity.

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