The maker of the mpox vaccine is looking at ways to dramatically scale up its production capacity to prepare for a potential threat from smallpox.
Bavarian Nordic CEO Paul Chaplin said the rapid spread of mpox last year was a wake-up call for the company, which is based in Denmark.
“If it wasn’t mpox but it was smallpox, we are completely at the wrong scale,” Chaplin told CNBC in an interview.
“We’re looking at ways we can dramatically change the way we manufacture to increase our scale,” he said.
Mpox is in the same virus family as smallpox. Bavarian Nordic’s Jynneos vaccine is approved by the U.S. Food and Drug Administration to protect against both pathogens.
Previously known as monkeypox, the World Health Organization changed the name to mpox last year to reduce stigma.
Bavarian Nordic plans to simplify its production process so it can easily partner with other manufacturers and scale up production capacity to hundreds of millions of doses in the event of an emergency.
The company’s current production capacity is tens of millions of doses.
Smallpox was eradicated from the world in 1980 after a successful global vaccination campaign. Though the risk of the virus returning is low, some governments don’t want to take any chances.
“There are concerns either through reengineering or accidental outbreaks from containment, or other terrorist activities that it could be reintroduced,” Chaplin said of smallpox.
Smallpox was one of the most deadly diseases known to humankind. It had a mortality rate of up to 30% depending on the strain, according to the WHO.
In the wake of the mpox epidemic, the European Union’s Health Emergency Preparedness and Response Authority and at least two European national governments have shown interest in stockpiling the Jynneos vaccine for use against smallpox, Chaplin said.
“Last year it was all about mpox. And now it’s a mixture of mpox, but also more strategic stockpiling, including the smallpox indication,” Chaplin said of discussions about future orders.
“The discussions have definitely intensified and increased,” he said.
The U.S. has a long-standing stockpile of more than 100 million doses of an older smallpox vaccine, called ACAM2000.
Bavarian Nordic will finish delivering an order of 5 million Jynneos doses for the U.S government in the first half of this year. That contract was signed during the mpox outbreak.
Mpox as a warning
Once limited mostly to Africa, mpox spread suddenly and rapidly around the world last summer, taking public health authorities and Bavarian Nordic by surprise.
Unlike smallpox, mpox is rarely lethal, but the virus can be deadly for people with severely compromised immune systems. And the skin lesions associated with the disease can cause excruciating pain.
Bavarian Nordic only had several thousand finished doses of Jynneos on hand when the United Kingdom reported the first known case of the epidemic to the WHO last May.
“We sold the entire stock to the U.K. government, thinking that this was, as usual, an isolated case,” Chaplin said.
Sporadic cases of mpox had occurred in countries outside Africa by travelers in the past. In 2003, there was a small outbreak in the U.S. that came from imported animals.
But when other countries in Europe started reporting cases of the virus last year, it became clear something unusual was happening, Chaplin said.
“The phone started ringing and we realized we were in a situation that we hadn’t seen before,” Chaplin said.
The virus has since exploded to more than 87,000 cases, with 120 deaths, across 110 countries, according to WHO data.
The global epidemic is the largest in the observed history of the virus. The U.S. had the worst outbreak with more than 30% of reported cases worldwide.
At that time, “We had no plans to manufacture Jynneos,” Chaplin said. “We manufacture other vaccines and our order book was full, but we had to make the decision there and then, we need to change all our manufacturing plants and just manufacture Jynneos.”
Bavarian Nordic distributed more than 4 million doses of Jynneos to over 70 countries from May to December of last year, Chaplin said.
More production capacity needed
Mpox since last year has spread primarily through sexual contact among gay and bisexual men.
But the rate of new cases of the virus has declined dramatically as vaccine distribution ramped up and communities at risk had better information about what precautions to take.
Bavarian Nordic estimates that the potential demand for the mpox vaccine could reach tens of millions of doses.
The company’s current annual production capacity is between 15 and 20 million doses, Chaplin said.
“It was contained in that risk population, it didn’t spread,” the CEO said of last year’s outbreak. “If that’s the way it manifests itself again, I think we can manage.”
While mpox spreads mostly through close physical contact, smallpox infects people primarily through respiratory droplets, which means the virus has greater potential to spread widely.
And Bavarian Nordic’s annual production capacity for Jynneos wouldn’t be sufficient to deal with a wide-spread outbreak of smallpox, Chaplin said.
“We will need many, many more doses. We need to think about how we are better prepared,” the CEO said.
Bavarian Nordic’s current production capacity is constrained by the fact that the weakened virus used in the vaccine is produced from chicken cells that come from special hen eggs.
Bavarian Nordic has developed a permanent avian cell line that will simplify production and make it easier to bring in other manufacturers in an emergency, Chaplin said.
The company plans to introduce the new cell line in the next 18 months, he said.
Though smallpox was eradicated more than 40 years ago, there are still two known stockpiles of the virus.
The U.S. Centers for Disease Control and Prevention and the Russian State Centre for Research on Virology and Biotechnology each have smallpox samples for research purposes. They are the only two labs in the world approved to hold the virus.
The World Health Assembly, a United Nations entity, has repeatedly passed resolutions calling for the eventual destruction of the remaining smallpox samples.
The U.S. in 2011 pushed back against that effort, contending that the samples needed to be preserved for the time being to develop countermeasures in the event someone deliberately reintroduced smallpox, or the virus escaped from an undisclosed stockpile somewhere in the world.
The U.S. has 360 samples stored by the CDC in Atlanta. And Russia has 120 samples stored at its research facility in a small town called Koltsovo in Siberia, according to a WHO report from 2021.
They are used to research the development of diagnostics, antivirals and vaccines.
In 2019, a gas cylinder exploded at the Russian facility and caused a fire. No biological material was stored in the room where the blast happened, according to a statement from Russian authorities at the time.
The Soviet Union had a biological weapons program until the early 1990s, which included storing dozens of tons of smallpox, according to congressional testimony from Ken Alibek, that program’s former deputy director, who had defected to the U.S.
And in 2018, scientists in Canada constructed a horsepox virus in the lab, raising concern that the same method could be used to synthesize smallpox.
Chaplin said, “It’s known that Russia weaponized smallpox and grew up large quantities, so there’s concerns that maybe that has gotten into the hands of other people.”
“If you can reengineer a related virus like horsepox, you can engineer variola, which is the smallpox virus that infects humans,” he said.
Declining population immunity
Smallpox vaccines have not been routinely administered to the general population in decades. As a consequence, many people around the world do not have protection against the virus.
“Collective immunity in the human population since that time is not what it was at the time of smallpox eradication,” Dr. Rosamund Lewis, head of the WHO’s smallpox secretariat, said last summer.
Most people under the age of 40 aren’t protected because they were born after smallpox vaccination stopped, Lewis said.
The U.S., the WHO and other countries keep stockpiles of smallpox vaccines in the event of an emergency, but many of these shots use older technology.
The overwhelming majority of the U.S. smallpox vaccine stockpile is ACAM2000. Though effective at protecting against smallpox, ACAM2000 can cause serious side effects in pregnant women, people with skin conditions like eczema and those with weak immune systems.
This is because ACAM2000 uses a mild virus strain related to smallpox that can still spread in the human body of the vaccinated patient and to others who are unvaccinated. The vaccine cannot cause smallpox.
But the vaccine virus can spread to a pregnant women’s fetus and result in still birth. It can also grow uncontrollably and cause dangerous infections in people with compromised immune systems and those with skin conditions.
People who receive ACAM2000 can also spread the virus in the vaccine for several weeks to others who are unvaccinated. This could result in severe side effects if someone in the vaccinated individual’s household is in any of the risk groups.
The Jynneos vaccine uses a weakened virus strain that cannot spread and does that not cause the side effects associated with ACAM2000.
Jynneos originally was developed with support from the National Institutes of Health for people who cannot take shots like ACAM2000.
Jynneos is administered in two doses taken four weeks apart.
One dose of the Jynneos vaccine is estimated to be 80% effective at preventing disease from mpox, according to scientific studies.