More than two years into the COVID-19 pandemic, U.S. health officials are grappling with how to update vaccines to best protect Americans from the ever-changing coronavirus.

On Wednesday, a U.S. Food and Drug Administration vaccine advisory panel spent hours discussing key issues for improving the vaccine and developing future boosting activities. They did not draw any firm conclusions.

Questions facing experts include how often vaccines are updated for new strains, how effective they are to be approved, and whether updates should be coordinated with global health authorities.

Last week, the FDA authorized a fourth dose of a Pfizer or Moderna vaccine for anyone 50 or older and some young adults with severely compromised immune systems. This is an effort to get ahead of another possible surge.

But Dr. Peter Marks, the FDA’s head of vaccines, acknowledged at the meeting that “we simply can’t have booster vaccinations as often as we do now.” He called the latest booster update a “stop-and-break” measure to protect vulnerable Americans, Meanwhile, regulators decide whether and how to adjust current vaccines.

Marks warned that waning vaccine protection, new variants and cooler autumn weather could increase the risk of more surges.

“Our goal is to stay ahead of future mutations and outbreaks and ensure we do our best to reduce the number of illnesses and deaths from COVID-19,” Marks said, adding that he expects the vaccine team to hold an update in the coming months. Multiple meetings.

Some of the key questions discussed by the group:

How should the U.S. decide when to roll out future rounds of boosters?

One area where experts seem to agree is that vaccines should be judged on their ability to prevent serious illness that leads to hospitalization and death.

“We need to focus on the worst-case scenario, severe disease, and when we lose the battle, we need to change the strain,” said Dr. Mark Sawyer of UC San Diego.

Measured in this way, the current vaccine works very well.

Federal scientists recently reported that during the last omicron-driven surge, two doses of the vaccine were nearly 80 percent effective against needing a ventilator or death, while a booster boosted that protection to 94 percent.

But only about half of Americans who were eligible for a third shot got one. Continuing to ask Americans to get a boost every few months is unsustainable, many experts say.

A CDC team member suggested that 80 percent protection against severe disease could be the criterion for evaluating vaccines.

“I think we may have to accept this level of protection and then use other alternatives to protect individuals through treatment and other measures,” said Dr. Amanda Cohen, chief medical officer at the CDC.

Presentations at the conference by government health officials and independent researchers highlighted the challenges of predicting when the next major COVID-19 variant will emerge.

Based on currently available data, major new strains like omicron could emerge every 1.5 to 10 years, said Trevor Bedford, a disease modeler at the Fred Hutchinson Cancer Research Center. Given this unpredictability, researchers will need methods to quickly determine whether current vaccines are effective against emerging variants.

What is the process for updating vaccines to deal with new variants?

All three COVID-19 vaccines currently in use in the United States are based on the original coronavirus version that emerged in late 2019. Updating a vaccine will be a complex task that may require coordination between the FDA, manufacturers and global health authorities.

To speed vaccines to market, the FDA relies on research shortcuts to judge effectiveness, primarily their early effects on immune system antibody levels. Some panelists said Wednesday they hoped to get more rigorous data from studies that track patients over time to see who gets sick or dies.

But this method may be too time-consuming.

Dr Ofer Levy, from Harvard Medical School, said: “We’re working on a puzzle where it’s difficult to generate all the data we want in a short amount of time when new variants emerge.”

A representative from the U.S. Biomedical Advanced Research and Development Agency outlined a narrow window that manufacturers could face to reformulate, study and mass-produce the updated vaccine by September.

Robert Johnson, BARDA’s deputy assistant secretary, said: “If you’re not ready for clinical trials by early May, I don’t think manufacturers have enough product to meet demand.”

The process of updating the annual flu vaccine offers one possible model, as a representative of the World Health Organization elaborated.

Twice a year, WHO experts recommend updating flu vaccines to target emerging strains. The FDA then submits the recommendations to its own vaccine panel, who vote on whether they make sense for the U.S., laying the groundwork for manufacturers to tweak the vaccine and begin mass production.

But COVID-19 has yet to settle into a predictable pattern like the flu. As the coronavirus develops, different strains may dominate different parts of the world.

Several experts said they needed more meetings with more data and FDA recommendations to decide on a strategy.

“We’ve never been here before. We’re all working together to do the best we can, and it’s very complicated,” said Oveta Fuller of the University of Michigan School of Medicine.