Covid boosters targeting omicron are coming: What you need to know

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Covid boosters targeting omicron are coming. Here’s what you need to know about them.

As early as this weekend, people in the U.S. may be able to walk into their local pharmacy and get a reformulated covid-19 booster, the first update to the shots since the pandemic started.

The Food and Drug Administration and the Centers for Disease Control and Prevention have signed off on the new mRNA booster shots from Pfizer-BioNTech and Moderna for adults and teens. These reworked versions of the original covid vaccines target both the virus variants currently circulating in the U.S. — BA.4 and BA.5 — and the original coronavirus strain.

But while the federal government authorized the original versions of the mRNA vaccines based on reams of clinical trial data demonstrating their safety and efficacy in people, the data on the newfangled boosters is much more limited. That doesn’t mean they’re not safe or not effective — but it does represent a change of strategy for public-health authorities and vaccine makers, as they try to adapt to the virus’s evolution and the country’s waning immunity.

Grid spoke with Jenna Guthmiller, an immunologist at the University of Colorado, about the new vaccines, the data regulators relied on to authorize them and what kind of protection they might provide as the U.S. heads into the fall and winter. This interview has been edited for length and clarity.

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Grid: Why do we need an updated booster shot now?

Jenna Guthmiller: This virus has changed so much since it popped up in humans almost three years ago that the original vaccines aren’t doing what they need to do as well as they were. It’s really so different at this point that updating the vaccine is necessary to generate antibody responses that can provide better protection against these new variants.

G: Regulators don’t have a lot of data on how these boosters aimed at BA.4 and BA.5 work in humans, but instead are relying on mouse data. Is that unusual?

JG: No, it’s not unusual. The data that is necessary to approve these boosters is different than what was needed for the first vaccine because we’re in a different place now than we were then.

When the original vaccines were developed, it was the first time that this vaccine was going into humans, so the threshold of approval was way higher to show that it’s safe, especially since it was heavily reliant on mRNA technology, which had not been approved in humans previously. Now we live in a completely different world where millions, if not a billion people have received an mRNA vaccine. We know that the safety profile of that platform is good.

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We also know the spike protein [the part of the coronavirus targeted by the vaccine] is safe. So by just changing the spike protein slightly, which is what this updated booster is doing, there’s really no reason to be concerned about safety.

To show the vaccine works, researchers rely on immunogenicity data [which shows that a vaccine induces an immune response]. In 2020, most people had no immunity, so it was easy to give them the vaccine and see this beautiful antibody response. Now, most people have some immunity, via infection, vaccination or both. That makes it really hard to have consistent immunogenicity data from people. But if you see that the updated vaccine induces an antibody response in mice [which limited data suggests it does], that is going to be highly indicative of it also inducing an antibody response in humans. To me, and I think to most immunologists, that is sufficient data to move forward with this being implemented in humans.

We’re in good hands with this vaccine. There’s not really any reason to be worried about there not being clinical trials on its immunogenicity and safety. It just really is not necessary at this point.

G: Are we moving more towards a vaccine regime closer to influenza then, where vaccines are reformulated without new clinical trials because we already know a lot about how influenza vaccines work generally?

JG: I think that’s where vaccine implementation is going to be moving, updating the vaccines may become a routine part of our yearly vaccinations. We don’t get efficacy data from clinical trials for flu vaccine updates, in part because there’s not any time to do so. But we know there’s a pretty standard level of effectiveness each year.

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In terms of implementation, there’s going to be some distinct differences between flu and covid. So for flu, the vaccine is generated by actually growing viruses [in chicken eggs]. So we have to identify viruses that are circulating, select one that not only fits the profile we want but can also be grown to sufficient quantities to be used in a vaccine. Then you have to actually inactivate it for the flu vaccine manufacturing. So that whole process actually takes quite a bit of time.

Whereas the covid vaccine is going to be much more adaptable with the mRNA technology because all we need is the sequence of the spike protein we want to use to update it, and then very quickly you can make that vaccine. So it will take less time.

G: This vaccine is formulated to target the variants that are dominating the U.S. now, BA.5 and BA.4. What happens if a new variant emerges this fall? Will this booster still provide protection? Are they still worth getting?

JG: Absolutely. We have to work with what is currently circulating or what we currently know about because there is no way to predict what future variants are going to look like.

So I think it’s appropriate to be moving forward with the BA.4 and BA.5 boosters. If future variants continue to be kind of this same omicron lineage, the immunity that you generate from BA.4 and BA.5 will provide robust protection against variants that are highly similar to BA.4 and BA.5. It’s not a matter of if, but when, a new variant pops up, likely this winter, that virus is going to look quite similar to that of the 4 and 5 variants. And as a result, you know, that immunity is going to be quite cross protective.


And I think this bears out by the fact that many people that were infected by omicron in this last winter’s waves are still highly protected against BA.4 and BA.5. Of course, there are reinfections, but generally those infections are very self-limiting. They’re mild symptoms and, ultimately, that shows how well that immunity is working, that you’re not getting really sick.

G: What happens if the next variant looks way different, like omicron looked from delta?

JG: The fact that this is a bivalent booster could help in that scenario. By including things that are quite divergent from each other, like the original strain and omicron, that can allow a person or their B cells [immune cells that make antibodies] to have more cross-reactive immunity that might confer broader protection. So essentially, you’re improving your antibody responses against these new variants but also backboosting against older variants, and that can potentially fill in gaps.

Presumably by boosting with the original virus and omicron, the immunity conferred by the original virus could provide cross-reactive immunity to a new variant, and there’s quite a bit of data to show that. Immunity by delta doesn’t provide great protection against omicron, but immunity to the original virus does, so you don’t want to pigeonhole yourself down this omicron pathway.

G: The original vaccines were remarkably effective when they first came out, but that effectiveness waned over time. It seems like these boosters won’t be as impressive.

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JG: We live in a different world than we did when those first vaccines came out. Very few people had preexisting immunity, and the vaccine and the virus were very well matched, which was why that vaccine was so effective. But people’s immunity waned over time, which is normal, and new variants popped up. Combined, that resulted in this reduction of vaccine effectiveness. But we saw that when people got a booster, their antibody responses really improved.

That’s the motivation for getting this bivalent booster, we need to keep those antibody responses high to provide protection. And the reason that this booster now is so important, as opposed to a year ago when original boosters were being pushed, is that the virus is just so different than the original virus at this point. And so this bivalent booster is not only going to fill the gap of immunity of protective levels of antibodies, but it’s going to boost B cells and antibody responses that confer immunity against these new variants, and that’s going to really bridge the gap between the current immunity we have and the immunity that’s necessary for protection against these new variants.

G: A lot of people at this point have gotten exposed to omicron by an infection. What benefit does this bivalent booster offer them?

JG: It depends on when you were infected. If you were infected really recently, your antibody responses are at a ceiling, so they can’t really go any higher. If you were to get vaccinated, there’s not enough room for you to mount a new response. So that’s the case for people infected more recently. But if you were infected in January or February, those responses have waned enough that the gap between your antibody levels and their ceiling is substantially bigger than somebody that was infected last month. So if you get the vaccine, you are likely to see a good response against the vaccine. But if you were infected in June, July or August, getting the vaccine now isn’t going to do as much for you now because there’s no space to fill. But I’d still recommend getting the vaccine six months after your infection.

Thanks to Alicia Benjamin for copy editing this article.

  • Jonathan Lambert
    Jonathan Lambert

    Public Health Reporter

    Jonathan Lambert is a public health reporter for Grid focused on how science, policy and the environment shape our collective well-being.