Government advisers debated Tuesday if Americans should get a modified COVID-19 booster shot this fall — and exactly how best to update it to fight a virus that surely will change even more by then.

“That’s the problem — we’re being asked to more or less have a crystal ball today,” said Dr. Arnold Monto of the University of Michigan, who heads the Food and Drug Administration’s vaccine advisory committee.

Current COVID-19 vaccines have saved millions of lives globally and those used in the U.S. still offer strong protection against hospitalization and death — especially after a booster dose. But their ability to block infection markedly dropped when the super-contagious omicron mutant emerged.

Pfizer and Moderna tested shots updated to better match the omicron that surged over the winter, but that first mutant has disappeared — replaced by its genetically distinct relatives. The two newest omicron cousins, called BA.4 and BA.5, now make up about half of U.S. cases, according to the Centers for Disease Control and Prevention.

That makes for a tough decision on how to tweak the shot recipe, and “our goal is to have the best possible match” to blunt an expected COVID-19 surge this fall and winter, FDA vaccine chief Dr. Peter Marks said Tuesday.

While people vaccinated and boosted have good protection against COVID-19’s worst outcomes, it has slipped some, said CDC epidemiologist Heather Scobie, describing an increase in omicron-sparked hospitalizations among older adults.

Only about half of vaccinated Americans ever got that all-important booster. And while a second booster that’s recommended for people 50 and older again restores protection, only a quarter of those eligible have gotten one. Authorities hope an updated booster for fall might entice more interest.

Not a Modern Healthcare subscriber? Sign up today.

So what’s the evidence for a recipe change? Among the evidence Tuesday:

— Both Moderna and Pfizer found what scientists call “bivalent” shots — a combination of the original vaccine plus omicron protection — substantially boosted levels of antibodies capable of fighting that variant, more than simply giving another regular dose. Many scientists favor the combination approach because it preserves the original vaccines’ proven benefits, which include some cross-protection against other mutants that have cropped up during the pandemic.

Both companies found the tweaked shots also boosted antibodies against BA.4 and BA.5 but not nearly as many.

— Pfizer and its partner BioNTech also are offering up an omicron-only shot. Also in animal testing is vaccine further tweaked to match BA.4 and BA.5.

— A third company, Novavax, is awaiting FDA authorization of a more traditional kind of COVID-19 vaccine, protein-based shots. It argued that a booster of its regular vaccine promises a good immune response against the new omicron mutants.

Download Modern Healthcare’s app to stay informed when industry news breaks.

Another issue: Advisers to the World Health Organization recently said that omicron-tweaked shots may be beneficial as a booster rather than a replacement for first vaccinations — because they should increase the breadth of people’s protection against multiple variants.

“We don’t want the world to lose confidence in vaccines that are currently available,” said Dr. Kanta Subbarao, a virologist who chairs that WHO committee.