US experts wrestle with updating Covid-19 vaccines

More than two years into the Covid-19 pandemic, U.S. public health officials are beginning to grapple with how to keep vaccines up to date to best protect Americans from the ever-changing coronavirus.

On Thursday, a panel of Food and Drug Administration (FDA) vaccine advisors spent hours discussing key issues about revising the vaccines and conducting future booster campaigns. They came to no firm conclusions.

Questions the experts faced included how often vaccines against new strains need to be updated, how effective they should be to justify approval, and whether updates should be coordinated with global health authorities.

Last week, the FDA approved a fourth dose of either the Pfizer or Moderna vaccines for people age 50 and older and some younger people with severely compromised immune systems. It is an attempt to forestall another possible rise.

But FDA vaccine chief Dr. Peter Marks, conceded at the meeting, “We just can’t refresh people as frequently as we do.” He called the latest booster update a “stopgap measure” to protect vulnerable Americans while regulators decide if and how current vaccines should be optimized.

Marks warned that falling vaccine coverage, new variants and colder weather in the fall could increase the risk of further surges.

“Our goal here is to stay ahead of future variants and outbreaks and to ensure we do our best to reduce the number of illnesses and deaths from Covid-19,” Marks said, adding that he is in expect more meetings of the Vaccine Panel in the coming months.

Some of the key questions discussed by the panel:

How should the US decide when to launch future rounds of refresher shots?

One area where experts seemed to agree was that vaccines should be judged on their ability to prevent serious diseases that lead to hospitalization and death.

“We need to focus on the worst case scenario, which is serious illness, and we need to change strains if we lose this fight,” said Dr. Mark Sawyer from the University of California, San Diego.

As a result of this measure, current vaccines have held up remarkably well.

During the most recent omicron-driven surge, two vaccine doses were nearly 80% effective against the need for a ventilator or death — and a booster shot increased that protection to 94%, federal scientists recently reported.

But only about half of Americans entitled to a third shot got one. And many experts said it was unsustainable to keep asking Americans for a refresher every few months.

A panelist from the Centers for Disease Control and Prevention suggested that the 80 percent protection against serious diseases could become the standard for evaluating vaccines.

“I think we may need to accept that level of protection and then take other alternative avenues to protect individuals with therapeutics and other measures,” said Dr. Amanda Cohn, CDC’s Chief Medical Officer.

Presentations by government health officials and independent researchers at the meeting underscored the challenges of predicting when the next major Covid-19 variant could emerge.

Trevor Bedford, a disease modeler at Fred Hutchinson Cancer Research Center, said that based on the data currently available, a key new strain like Omicron could emerge every 1.5 years to once every decade. Given this unpredictability, researchers need methods to quickly determine whether current vaccines are effective against emerging variants.

What is the process for updating vaccines to address new variants?

All three Covid-19 vaccines now in use in the US are based on the original version of the coronavirus that was released in late 2019. Updating vaccines will be a complex task that will likely require coordination between the FDA, manufacturers, and global health authorities.

To speed the vaccines’ introduction to market, the FDA relied on research cuts to assess effectiveness, primarily looking at their early effects on immune system antibody levels. A number of panelists on Wednesday said they wanted more rigorous data from studies tracking patients over time to see who gets sick or dies.

But this approach would probably be too time consuming.

“We face a problem here because it will be difficult to generate all the desired data in a short time when a new variant emerges,” said Dr. Ofer Levy of Harvard Medical School.

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

“If you’re not on your way to a clinical trial by early May, I think it’s going to be very difficult to have enough product from all manufacturers to meet demand,” said Robert Johnson, BARDA associate assistant secretary.

The annual influenza vaccine update process offers a possible model, as outlined by a representative of the World Health Organization.

Twice a year, WHO experts recommend influenza vaccine updates to target emerging strains. The FDA then brings these recommendations to its own vaccines panel, which votes on whether they make sense for the US, thereby setting the stage for manufacturers to fine-tune their settings and begin mass production.

But Covid-19 has not yet settled into a predictable pattern like the flu. And as the coronavirus evolves, different strains may become dominant in different regions of the world.

Several experts said they would need more meetings with more data and suggestions from the FDA to decide on strategy.

“We have never been here. We all work together to do our best and it’s very complex,” said Oveta Fuller of the University of Michigan Medical School.

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