HOLLY SPRINGS, N.C. ‒ A quiet effort to prevent the next global pandemic began rolling off an assembly line this summer behind the gates of an office complex in suburban Raleigh.
In this sprawling factory, sheltered by thick pine groves, workers at CSL Seqirus are bottling millions of doses of a new vaccine targeting the H5N1 bird flu virus.
The virus, which first emerged in wild birds around 1997, has been spreading this year among dairy and poultry farms across the United States.
Thirteen farmworkers have been infected with the virus this year, some suffering eye redness, others a cough. No one became sick enough to require hospitalization, although, in other countries, about half of the people diagnosed with H5N1 over the years have died.
The virus is not being passed from person to person – and that is key to why public health officials aren’t hitting the panic button. Because the risk to the general public remains low, the federal government doesn’t think it’s worth vaccinating anyone against H5N1 yet – even the farmworkers most at risk for getting sick from infected chickens or cows.
But behind the scenes, officials are getting ready at Seqirus’ advanced facility in the biomanufacturing hub of Holly Springs.
Already, 4.8 million doses of a potential vaccine are sitting in an undisclosed Seqirus distribution center, ready for delivery if needed.
“An exercise like this gives our partners a chance to exercise that muscle, to make sure that the manufacturing’s there,” Dawn O’Connell, assistant secretary for preparedness and response for the U.S. Department of Health and Human Services, told USA TODAY during an exclusive tour of the vaccine factory in late July.
In past disease outbreaks, she said, getting enough vaccine made in time to stop individual infections and slow the spread of disease has been the government’s “Achilles’ heel.”
So here, in the heart of North Carolina’s coveted Research Triangle, winding conveyor belts and hanging robotic arms are filling one thumb-sized glass vial at a time to avoid the next global pandemic.
True success would mean at some point the contents of those vials could essentially be flushed down the toilet – because bird flu no longer poses a theoretical threat to human health.
But at a time when the virus seems to be spreading to new farms every week, when America’s healthcare system and treatment of farmworkers means infections are likely going undetected and fall flu season is rapidly approaching, public health officials say there’s no such thing as being too careful.
“You want to prepare for the worst case,” said Dr. Raj Panjabi, who oversaw pandemic preparedness at the White House from 2021 to 2023 as a special assistant to President Joe Biden. “This gets the engine moving.”
On the production line
Through several security doors at the Seqirus facility, scores of workers in white zip-up plastic suits, hairnets and goggles worked along conveyor belts carrying small tubes along a packaging line.
Seqirus’ packaging lines are capable of producing 2 million flu vaccine doses every two weeks, said Jonathan Kegerise, vice president of manufacturing and the site head for the facility in Holly Springs. The 4.8 million doses of H5N1 were slotted in between batches of seasonal flu and didn’t affect the production of those shots.
Robotic arms filled and capped vials as workers stood watch and prepared machines for the next batch. Along the way, lights flashed as cameras captured images of the vials for quality control. They would undergo additional inspections before they were packed away, ready for shipping if the federal government decided the H5N1 vaccines were needed.
The liquid was mainly divided into 10-dose vials. Seqirus produced an additional 250,000 pre-filled, single-dose syringes for times when opening a 10-dose vial would be wasteful.
The H5N1 vaccine had already been manufactured at the same Seqirus facility and stored at temperatures between 35.6 and 46.4 degrees Fahrenheit. Concentrated doses are made ahead of time as part of the national stockpile.
The vaccine has now been poured into vials allowing public health officials to more easily distribute doses if they are needed.
Making the substance for the doses takes about a month, followed by a day to formulate a batch, another day to fill the vials, and one last day to inspect and package them.
Seqirus is producing all 4.8 million doses under a $22 million agreement with the federal government, the company said.
Two types of vaccines are being prepared as defenses against the H5N1 virus. In addition to the vaccine being readied at Holly Springs, in July, the government also directed $176 million to Moderna to develop mRNA influenza vaccines, including for H5N1.
The two vaccines use different technologies – mRNA can be made faster, in case a pandemic is spreading quickly; the more traditional, cell-based vaccine rolling off these assembly lines takes longer to produce.
It makes sense to now complete the cell-based vaccines that are already in the national stockpile, said Dr. Nahid Bhadelia, the founding director of Boston University’s Center on Emerging Infectious Diseases. She told USA TODAY an mRNA vaccine could help if the virus changes enough that a new vaccine has to be developed.
Still, Bhadelia, who worked in the Biden administration during COVID-19, worries that Congress hasn’t allocated enough money to get ahead of the bird flu virus.
“Nothing can happen without money,” she said.
The vaccine we have now
Scientists hope the vaccine being poured into vials here would protect someone against a severe H5N1 infection, but they aren’t sure.
So far it has been tested only in ferrets, the animal typically used by labs to test flu vaccines. Seqirus already manufactures an H5N1 vaccine that FDA has determined is safe and effective. This new bird flu vaccine replaces the H5N1 strain with the circulating virus.
The first human trials for the new vaccine have begun, starting with healthy people to ensure the vaccine triggers the desired effect on the immune system. Those results are expected later this year.
At this point, researchers believe the vaccine coming off this assembly line will be effective, but it’s not guaranteed, Bhadelia said.
It’s also possible that by the time the virus transforms enough to become truly dangerous to large numbers of people, it will have changed so much that the vaccine that has been prepared here will no longer work, said Dr. Paul Offit, an infectious disease and vaccine expert who directs the Vaccine Education Center at Children’s Hospital of Philadelphia.
Even if the vaccine works well, there’s the problem of scaling up production and getting it to enough people fast enough.
To work effectively, the vaccine requires two doses to be delivered at least three weeks apart. It’s unclear how much protection someone gets after the first dose. In emailed responses, Seqirus wouldn’t say when the vaccine doses expire and when they’d have to be replaced.
Delivering them to people will be challenging, too.
With the COVID-19 vaccine, it was more difficult than expected to get the doses from the warehouses to vaccine clinics and into arms. Cold storage, bottle size and other factors posed problems that had to be resolved on the fly.
The National Biodefense Plan, which Panjabi oversaw, was launched in 2022 with the goal of providing enough vaccines for all at-risk populations within four months of a pandemic’s start.
If bird flu could be addressed early enough – contained before it spreads beyond farmworkers and their families and not spread among the general public – it would be much easier to make enough vaccine and deliver it to the right people in four months’ time.
That’s why some public health experts believe farmworkers should be offered vaccines before the virus has a chance to become more dangerous.
Vaccinating farmworkers would not reduce the number of people who become severely infected with bird flu, Bhadelia said, but she thinks they should be offered it as part of a research trial. “It will just potentially help with severe disease and to further our scientific understanding,” she said.
Still, Dr. Nirav Shah, principal deputy director for the Centers for Disease Control and Prevention, doesn’t think the time is right to start vaccinating anyone.
H5N1 has not caused serious cases of disease, it is not spreading person-to-person, and its genetics haven’t changed substantially since the vaccine was developed against it. Right now, he told reporters in late July, a readily available antiviral is a better tool for anyone infected or exposed than the vaccine would be.
“The H5 vaccine, at this moment in time, is not performing the job that we really need,” Shah said.
A different vaccination
Finland made a different decision. In June, Finnish officials began distributing 20,000 doses of a different Seqirus vaccine to people ages 18 and older exposed to animals they believed were susceptible to bird flu, including workers in the country’s mink industry
In late July, fewer than 200 people in Finland had received shots, and the vaccines must be used by mid-September before they expire, said Mia Kontio, chief specialist for the Finnish Institute for Health and Welfare’s infectious disease control and vaccinations. Many Finns are on vacation in the summer, she added, so August is going to be “very hectic” to quickly immunize people with the two-dose regimen.
The return of wild migratory birds in the fall, potentially carrying the virus, add to the urgency, she said.
We felt that it’s our responsibility to actually do something if we can,” Kontio told USA TODAY. “Because the situation might change very quickly.”
Where are we now?
In the U.S., federal officials expanded regulations on interstate transportation of livestock in recent months. They’ve added alerts on products such as unpasteurized milk, and warned that shared equipment can spread the virus among animals.
They have also provided personal protective equipment, such as N95 respirators, goggles and gloves, in states affected by bird flu.
Recently, federal officials launched an effort to vaccinate livestock workers against the seasonal flu. That vaccine doesn’t offer any protection against H5N1, which is a different strain of influenza, said Shah, from the CDC.
Getting the seasonal vaccine, however, could prevent someone from simultaneously having both the seasonal flu, which is highly contagious, and H5N1, which can be extremely dangerous. A worst-case scenario would be a virus that combines the two, Shah said.
Flu viruses are known to exchange genes with one another, so such a combination is always possible.
“Viruses are sort of smart,” May Chu, a clinical professor of epidemiology at Colorado School of Public Health, told USA TODAY. “Our bodies offer the place where they replicate. And so if you don’t let the virus into you, you aren’t going to be contributing to the genetic growth of this virus. This is what you want to stop. Because the more people get infected, the more viruses grow, and the more chances of the genetic variant arising of deleterious effect.”