close-up of health care injecting arm of patient with COVID booster

Is the Bivalent Booster Worth It?

Conflicting reports of the bivalent booster’s effectiveness in preventing SARS-CoV-2 infections have created confusion among the public.

David D. Ho

David D. Ho

The current COVID booster contains two versions of the virus’s spike protein: one from the original virus (now extinct) and another from the BA5 omicron variant, which was dominant in the United States earlier this fall.

The booster’s efficacy in people had not been studied before the booster was approved by the FDA, though animal studies have found it generates better protection against widely circulating omicron variants.

Statements in the past weeks from vaccine manufacturers maintain that the bivalent booster is better than the original booster at increasing antibodies. But an unpublished study conducted by David Ho, MD, director of the Aaron Diamond AIDS Research Center at Columbia University Vagelos College of Physicians and Surgeons, suggests that the new bivalent booster generates the same level of antibodies against omicron variants as the original booster. Harvard researchers have reported similar results. (The Columbia and Harvard studies are available as preprints on BioRxiv).

Even if the bivalent booster is only as effective as the original, “that doesn't mean people shouldn't get the bivalent booster,” Ho says.

“In our study we also found that the bivalent booster greatly increases the number of antibodies that neutralize the omicron variants. We still advocate boosting so that folks are better protected.”

We spoke with Ho about the study’s findings and what to expect this winter.

Did your findings surprise you?

Our result was a bit disappointing, because we all wanted to see the bivalent booster generate a superior antibody response against omicron, but our human data show that there’s not a lot of difference between the two types.

This wasn't a total shock. There’s a phenomenon known in vaccinology called immunological imprinting, which means your immune memory preferentially sees what it has seen before. So when a vaccine contains two different spike proteins, one that the immune system has seen before and one that it hasn’t, your immune system is going to react most strongly against the known variant, not omicron.

In retrospect, it may have been better to have created a booster that targets a single variant, the BA5 omicron variant.

A caveat of our findings is that we’ve only measured antibodies at one time point. There could be a difference later on, but we won't know that for a few months. It’s also possible that getting a second bivalent shot may make a difference.

What do you expect to happen with COVID this winter?

I think we're in for rough waters in terms of infections in the weeks and months to come, as public health restrictions have loosened and more people are gathering indoors without masks. But probably not in terms of severe disease and death. The more cases we have, certainly the more severe disease, hospitalization, and death we’ll have, along with cases of long COVID, but hopefully that will not happen to a significant percentage of those infected.

We have so many people in the United States who have been vaccinated, and a lot of people have been previously infected. That's going to really help protect much of the U.S. population from having severe illness.

We also know that the variants have not developed any mutations that lower the effectiveness of Paxlovid, so that should still be a useful antiviral this winter.

Will we have vaccines soon that prevent infections?

There's no question that the current vaccines are preventing severe disease and death. And that's quite important.

But we all would like to have vaccines that also block infection. There's considerable effort moving toward nasal vaccines that could perhaps induce a better response within the upper airway mucosa. And hopefully, that could protect infection better. But that's still a long way away based on what I see.

There’s also considerable effort directed toward developing what's called pan-sarbecovirus vaccines that will protect against all COVID-causing variants and maybe even protect against other SARS and related viruses. Those efforts are also rather nascent, I would say, and would take time to develop.


David Ho, MD, also is the Clyde '56 and Helen Wu Professor of Medicine and professor of microbiology & immunology at Columbia University Vagelos College of Physicians and Surgeons.