In a run-of-the-mill business park in Kvistgård, a Danish village about 25 miles north of Copenhagen encircled by forests, lies one of the most crucial solutions for controlling the global monkeypox outbreak. These are the manufacturing facilities of Bavarian Nordic, the biotech company that is the sole producer of the most advanced vaccine for monkeypox. Called Jynneos in the United States, Imvanex in Europe, and Imvamune in Canada, the vaccine is the only one that has been approved by the European Medicines Agency and the US Food and Drug Administration for preventing people from developing or transmitting monkeypox.
The problem? Bavarian Nordic’s manufacturing facilities have been shut until very recently, and most of the vaccine doses it produced before it closed are currently sitting frozen in plastic bags, not yet usable. Meanwhile, the monkeypox outbreak has been declared a public health emergency of international concern, with more than 27,000 cases—mostly traceable to sexual or skin-to-skin contact among men who have sex with men—in 88 countries.
In a desperately untimely twist of fate, Bavarian Nordic closed its bulk manufacturing facility in the spring of 2022 to focus on its other vaccine products, including vaccines for rabies and encephalitis. The company had expected to reopen the facility in the third quarter of this year, and it is “reopening as we speak,” Thomas Duschek, communications partner for Bavarian Nordic, told me. He says it will be operating at full speed within the next month or so, and will be reopening with two production lines as opposed to the previous one. The company is also considering moving to a 24-hour production cycle to meet demands, although this hasn’t happened yet, Duschek says. Bavarian Nordic may also postpone the production of other vaccines to prioritize production of the monkeypox vaccine.
The company is also looking at contracting other manufacturers to ramp up production. It has already inked a deal with a US company, the name of which remains confidential. The problem is that the vaccine is complex to make, so it would take months for another manufacturer to get up to speed. Even at Bavarian Nordic, Duschek reckons it will be half a year at minimum before newly produced vaccines start being shipped.
The WHO has said it thinks there are around 16 million doses of the vaccine available right now globally, which, by its estimates, should be enough to contain the outbreak. But there’s a snag, and it’s a big one: Most are still in their bulk form, meaning they still need to be transferred from those frozen bags into vials for use, a process known as “fill and finish”—and this will take several months, Bavarian Nordic says. The WHO is reportedly in talks with other manufacturers who could chip in and speed up the process. In the US, the New York Times reported that health authorities are negotiating with a factory in Michigan to help bottle 2.5 million doses.
The other catch is that most of these doses have already been snapped up by the US, despite only a quarter of global cases being located in the Americas, with no deaths reported.
But bizarrely, even though it owns most of the current stock, the US hasn’t secured a consistent supply of usable vaccines. The country has been stockpiling doses for years—to protect against smallpox, which it also works against, in the event of a bioterror attack—and has bought close to 30 million over the past two decades. However, the vast majority of the usable doses it ordered in the past expired sitting in freezers and were never replaced, despite the US having many more on order. (The country owns the equivalent of about 16.5 million doses in bulk form, Bavarian Nordic has said, and had been keeping a lot of it on ice while a method of freeze-drying the vaccine was being developed.) When the monkeypox outbreak hit the US, it had just 2,400 doses that were usable.
Now, bureaucratic fumblings on the part of the US government have made it difficult for the country to get its hands on more usable doses to replenish its stocks, even though it owns most of the bulk that’s already been made. In 2020, the US ordered 1.4 million usable doses of the vaccine from Bavarian Nordic, yet this June—when the monkeypox outbreak was beginning to proliferate across the country and the order was still outstanding—US authorities still dillydallied before requesting the company start fulfilling that request by shipping over some 370,000 doses sitting ready in Denmark.
For the rest of the order, the bulk form of the vaccine needed to be processed into usable doses at a new fill-and-finish plant that Bavarian Nordic had completed in 2021, but the FDA hadn’t at the time approved that facility for supplying materials to the US. This meant that on May 23, over 200,000 doses that could have gone toward fulfilling the US’ request from 2020 were delivered instead to European countries while the FDA finished up its inspection.
The FDA has now finally signed off the facility, meaning 786,000 more doses have since been shipped to the US. Up to the middle of July, the US also put in new orders for about 5 million more usable doses, but because of its tardiness earlier in the summer, by this point other countries had already snapped up the existing supply of ready-to-use vaccines—meaning that these newly ordered usable doses can be delivered only in 2023. In a press release from July 15, Bavarian Nordic said it expected to deliver nearly 7 million doses to the US in 2022 and 2023.
Outside of the US, the European Health Emergency Preparedness and Response Authority (HERA) has bought 160,000 doses for Europe. Health authorities in the United Kingdom recently said they had procured more than 100,000 vaccine doses, and Australia says it has bought 450,000 doses, with 100,000 arriving this year and the remainder in 2023. So even though the US has been slow to replenish its stockpile, it still has the biggest supply of Bavarian Nordic’s vaccine by far.
But this vaccine isn’t the only answer; alternatives do exist. One is ACAM2000, another vaccine that protects against smallpox. But it has its various downsides: It’s linked to some rare but serious side effects, specifically in pregnant people, infants, and immunocompromised people such as those with HIV, which has a higher prevalence among men who have sex with men. Administering it also requires special training. Even so, some experts are advocating that this vaccine be made available to those who choose to receive it with knowledge of the risks—especially considering the US is sitting on a giant stockpile of about 100 million doses. Alternatively, Japan also has a smallpox vaccine that could be used against monkeypox, called LC16, although it’s also associated with some unfavorable side effects.
At this point, mass vaccination campaigns have not been called for. At first, ring vaccination campaigns—where the close contacts of the infected are called to be vaccinated—were used. Now the WHO has moved to recommend targeting the vaccine toward at-risk communities, which includes health care workers and men who have sex with men.
The WHO is still weighing up the pros and cons of the existing vaccines, but it has put out a call to countries that are using vaccines to “collect and share critical data on their effectiveness,” as the picture remains pretty blurry given that all the vaccines were originally developed for smallpox—not monkeypox. WHO officials estimated at a July 27 press conference that 5 to 10 million doses would be sufficient to keep the outbreak under control under its current strategy—fewer than what is available in bulk, but much more than what could be quickly given to people right now. There are discussions around whether giving one dose of the Bavarian Nordic vaccine—or perhaps even less—could be sufficient given the shortages (it was designed as a two-dose vaccine).
Amid the scramble, this all brings a sense of déjà vu. The very first death from the outbreak occurred in Africa, which is the only continent where the virus is endemic—and yet it is also the only continent that has received no vaccine doses. Monkeypox outbreaks have been ongoing in parts of Central and West Africa for the past five years; to date, 75 people are suspected to have died from the virus across the continent, and cases are on the rise in Nigeria. The death count is likely higher, owing to limited testing.
And vaccine inequity is what got us to this point: African scientists made noise about the recent ongoing outbreaks but were largely ignored. “The lack of investment just keeps coming back to haunt us,” says Liz Breen, a professor at the University of Bradford in the UK who is an expert in health care supply chains. The Africa Centres for Disease Control and Prevention has called for the continent to be prioritized in the rollout. “If we’re not safe, the rest of the world is not safe,” said Ahmed Ogwell, the Africa CDC’s acting director.
The WHO has urged countries with vaccines to share them with those without. In June, it said it will set up a vaccine-sharing program, but has since released little information on when or how that will happen.
The supply is dependent, after all, on the pharmaceutical industry, which is driven by financial incentives, not a sense of moral duty that everyone should get what they need. “I would not be surprised if you find that in two years’ time, this company will be churning out billionaires,” says Sridhar Venkatapuram, a senior lecturer in Global Health and Philosophy at King’s College London. Bavarian Nordic’s expected revenue for the year has more than doubled already, and its share price has tripled. This means that the world is dependent on the output of a few companies to stem the outbreak. “I mean, God forbid any of these companies go under,” Breen says.
What this also means is that vaccines will be a scarce commodity in the coming months, nowhere more so than in low-income countries. And failing to control the outbreak means there’s a risk the virus could spill over and establish itself in new animal populations. What Covid—and now monkeypox—reveals is that tackling outbreaks as a domestic problem simply does not work. Leaders of rich countries and international organizations need to understand that “if there is an outbreak in some faraway country, it could be your problem within a month or a week,” says Venkatapuram. “That has really not gotten into people’s heads.”
