The Centers for Disease Control and Prevention currently recommends that people who are severely immunocompromised should get a fourth dose. But that recommendation may soon change, based on the recent flurry of corporate and regulatory activity around COVID-19 boosters.

BioNTech SE
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and Pfizer Inc.
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are seeking authorization for a fourth shot in people who are at least 65 years old, while Moderna Inc.
MRNA,
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in mid-March asked the FDA to allow all adults in the U.S. to get another booster.

“I don’t see a world where we do not provide an important vaccine booster to the American people in the fall,” CEO Stéphane Bancel told investors on Thursday.

The Food and Drug Administration announced this week that its vaccine advisory committee is set to meet April 6 to discuss a framework for future COVID-19 vaccines. The regulator said the meeting won’t focus on Comirnaty or Spikevax or other COVID-19 vaccine applications but is instead intended to more broadly examine the future of COVID-19 vaccines, including variant-specific shots and who should get them. 

“Here in this country, we’re looking at it and letting the data drive us,” Dr. Anthony Fauci, President Biden’s chief medical adviser, said Wednesday during a press briefing. “The FDA will call their [vaccine committee] to take a look at the long range of where we might go with new variants and where a fourth shot fits in with that. There’s also the immediate situation of looking at what we might do over the next few weeks to a month.”

And this is where the latest COVID-19 booster debate gets complicated. It’s not just about whether another round of shots is needed. It’s whether a booster should be based on the original Wuhan strain of the virus (as our current vaccines are) or on the omicron variant. It also has to do with timing: Are boosters needed right now? Will we need a round of shots in the fall, as suggested by Moderna’s Bancel? 

Then there’s the very American question of how it’s all going to get paid for. White House officials say there is only enough COVID-19 funding to allow the immunocompromised and seniors to get a fourth dose unless Congress agrees to provide more pandemic funds. (The Kaiser Family Foundation said Friday that there are only enough doses for 70% of seniors to get a fourth dose at this time.)

“Without more funding, we can’t procure the necessary vaccine supply to support fourth shots for all Americans,” Jeff Zients, the White House’s COVID-19 response coordinator until April 5, said at the same briefing. “Furthermore, if things change and there’s a need for a new vaccine, a new formulation — for example, a variant-specific vaccine — we won’t be able to secure doses for the American people.”

Putting aside the question of federal funding, there are still many unknowns about what the next phase of a pandemic vaccination program could look like in the U.S. 

When about 275 health care workers at a medical center in Israel were given a second booster, it only slightly increased their protection against omicron, according to correspondence published March 16 in the New England Journal of Medicine. The workers were immunized with either the Comirnaty or Spikevax booster four months after getting their third shot of the BioNTech/Pfizer vaccine.

“We observed low vaccine efficacy against infections in health care workers, as well as relatively high viral loads suggesting that those who were infected were infectious,” the researchers concluded. “Thus, a fourth vaccination of healthy young health care workers may have only marginal benefits.”

Research like this can help inform pandemic policy makers. It can also raise additional questions, including: Will the current COVID-19 boosters continue to protect people against the BA.2 subvariant if they get a fourth dose now? Will the omicron-specific or pan-SARS-CoV-2 vaccines in development do a better job protecting against the variants that are currently in circulation?

“The problem is the vaccines were developed against the original Wuhan strain,” said Dr. Carlos del Rio, an infectious-disease physician and executive associate dean of the Emory School of Medicine, told MarketWatch last month. “As variants have evolved, we’ve seen a decrease in the efficacy of vaccines. The vaccines stay the same, but the variants are changing. You can start doing a vaccine for specific variants, but then as the virus evolves, there’ll be more variants. More strategically and more important is to develop a pan-coronavirus vaccine.”

The U.S. Army is in the process of analyzing Phase 1 data for a pan-SARS-CoV-2 vaccine, which targets the original strain of the virus and all variants of concern. The experimental shot may also be effective against the original SARS from 2002. Moderna is working on three types of boosters: a second dose of its already authorized booster, an omicron-specific vaccine, and a bivalent vaccine that equally targets the original wild-type virus and the omicron strain. BioNTech and Pfizer are also developing an omicron-based vaccine.

This next generation of COVID-19 vaccine candidates aims to go beyond the original strain of the virus, which was first identified in Wuhan, China, back in 2019. Instead, they aim to protect against omicron, now the most dominant strain of the virus worldwide, or target SARS-CoV-2 variants of concern. One day there may even be a “pan-coronavirus” vaccine for all coronaviruses, including the ones that cause the common cold.  

“If we ever get there, that will take years,” Fauci said March 2. “But what we’re focusing on first is a pan-SARS-CoV-2 vaccine, which means a vaccine that would be highly effective against ancestral strain — alpha, beta, delta, omicron — or any future SARS-CoV-2 that we might experience. I believe that is much, much closer than the pan-coronavirus vaccine.”

Medical experts still make it a point to mention how well the COVID-19 vaccines have performed, particularly when it comes to preventing the kind of severe disease that leads to hospitalization and death, even against the new variants that emerged in 2021.

The goal now, however, is to develop an even more effective set of vaccines and treatments, in order to prepare for an uncertain future. 

“How can we try and design a vaccine that is able to combat multiple different types of variants?” asks Dr. Rachael Piltch-Loeb, an associate research scientist at the NYU School of Global Public Health and a preparedness fellow at Harvard T.H. Chan School of Public Health. “That effort is certainly worthwhile as we think about the future of the virus, which is, from my perspective, a virus that we will continue to grapple with for years to come. The need or desire for a vaccine for people who are willing to get it will be alive and well for a long period of time.”