Bird flu threatens egg-based vaccines | NC Health News

By Arthur Allen

Anytime there’s even the slightest bit of news about a new flu pandemic, scientists start buzzing about eggs.

People worried about the flu in 2005, 2009, and now because millions of fertilized chicken eggs are still used as the main ingredient in making vaccines to protect people against new flu pandemics.

“It’s almost ludicrous to use 1940s technology for a 21st century pandemic,” said Rick Bright, who led the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA) during the Trump administration.

It’s not surprising, Bright says, that current stockpiles of H5N1 avian influenza vaccines provide only moderate immunity, despite requiring two injections and 90 micrograms of antigen. “In the United States alone, it would take 900,000 chickens to lay eggs every day for nine months,” he says.

And that’s only if the chickens aren’t infected.

The spread of the avian influenza virus has devastated bird flocks (as well as killed domestic cats and other mammals), infected cattle in at least nine states and at least three people in the United States, and has once again focused public health attention on the possibility of a global pandemic.

As of May 30, the only confirmed cases were dairy workers in Texas and Michigan, who developed eye irritation. Two quickly recovered, but the third developed respiratory symptoms and is being treated at home with antiviral drugs. However, the virus has spread across a large area and into multiple species, and further mutations could lead to a virus that can spread from person to person via the air.

If so, prevention starts with the eggs.

To make the flu vaccine material, the virus is grown in millions of fertilized eggs. Sometimes the virus doesn’t grow well, or mutates so that the vaccine product stimulates antibodies that don’t neutralize it, or the wild virus mutates so that the vaccine doesn’t work. And there’s always the frightening possibility that wild birds will carry the virus into the chicken coops needed to make the vaccine.

“If the roosters and hens die, there’s no vaccine left,” Bright said.

Researchers and governments have been exploring alternatives since the H1N1 swine flu pandemic swept across the globe in 2009, before any vaccines were in production. Billions of dollars have been invested in vaccines produced in mammalian or insect cell lines that don’t pose the same risks as egg-derived vaccines.

“We all know that cell-based vaccines are better, more immunogenic, and better produced,” said Amesh Adalja, an infectious disease expert at the Johns Hopkins University Center for Health Security, “but they’re at a disadvantage because of the leverage of egg-based manufacturing.”

CSL Securus and Sanofi, which make cell-based influenza vaccines, have also invested billions in egg-based production lines but are reluctant to replace them.It’s hard to blame the companies, said Nicole Lurie, who served as undersecretary for Health and Human Services for preparedness and response under President Obama and is now executive director of CEPI, a global epidemic prevention nonprofit.

“Most of the vaccine companies that responded to pandemic diseases like Ebola, Zika and COVID ended up losing a lot of money,” Lurie said.

The exception was the mRNA vaccines being developed for COVID-19, but as public interest waned, even Pfizer and Moderna had to discard hundreds of millions of doses of unwanted vaccine.

David Boucher, director of infectious disease preparedness at the U.S. Department of Health and Human Services’ Office of Strategic Preparedness and Response, said Pfizer and Moderna are testing seasonal flu vaccines using mRNA, and the government is soliciting bids for an mRNA pandemic flu vaccine.

“We definitely can’t fight an H5N1 pandemic with an egg-based vaccine,” said Bright, who has invested $1 billion in a cell-based flu vaccine factory in Holly Springs, N.C. But at this point, he has little choice.

BARDA has stockpiled hundreds of thousands of doses of an H5N1 strain vaccine that stimulates the production of antibodies that are thought to neutralize the current circulating virus, and it could produce millions more doses within weeks and up to 100 million doses within five months, Boucher told KFF Health News.

But the vaccines currently in the national stockpile aren’t perfectly matched to the strains in question: Even though the two-dose shot contains six times as much vaccine material as a regular flu shot, the stockpiled vaccines are only partially effective against the strains that were circulating at the time they were made, Adalja said.

But BARDA is currently supporting two clinical trials using vaccine candidate viruses that “match well with those found in cattle,” Boucher said.

Flu vaccine makers are just starting to prepare vaccines for this fall, but the federal government may eventually require them to switch production to strains targeted at the pandemic.

“We don’t have the capacity to do both,” Adalja said.

For now, ASPR has a large stockpile of pandemic vaccine and is identifying a manufacturing facility that can bottle and finish 4.8 million doses of the vaccine without halting seasonal flu vaccine production, ASPR Chief Executive Dawn O’Connell said May 22. U.S. officials began working to move away from egg-based vaccines in 2005, when avian flu first hit the world, and picked up steam after the 2009 debacle. But “with the resources available, leveraging the seasonal infrastructure is cost-effective and provides the greatest value for U.S. taxpayers, and that’s still mostly egg-based,” Boucher said.

Flu vaccine companies “have a system that’s working well right now to get us there with making seasonal vaccine,” he said, and without financial incentives, “I think we’re going to be relying on eggs for a while.”