Lea Suzuki/San Francisco Chronicle via AP
A pharmacist removes a tray of vials of the Jynneos vaccine, in the vaccine hub at Zuckerberg San Francisco General Hospital, July 29, 2022.
As the monkeypox outbreak appears to slow in the U.S., countries around the world are still waiting to get access to the vaccine, called Jynneos. African countries where monkeypox is endemic, including the Democratic Republic of Congo, have no doses, despite recording multiple deaths. All of Latin America is expected to get just 100,000 doses this year.
One small Danish corporation, Bavarian Nordic, controls global supply of Jynneos. That control gives it the power to shape the global response. For instance, after the Biden administration announced a plan to stretch supply of Jynneos by splitting doses, the head of Bavarian Nordic reportedly threatened to cancel U.S. orders. “People are begging for monkeypox vaccines, and we’ve just pissed off the one manufacturer,” one U.S. official told The Washington Post.
Bavarian Nordic recently told investors it set one price for the vaccine. “We use the same approach for everyone.” That price appears to be above $100—almost certain to keep Jynneos out of reach for much of the world.
The control exercised by Bavarian Nordic is all the more galling because it turns out that almost all the pioneering work on Jynneos was done with public dollars and public science in Germany and the U.S. The story of how this happened raises sharp questions about who decides how medicines are developed, produced, and distributed in a global health emergency.
The story of the monkeypox vaccine begins in Germany in the 1950s, when the Bavarian State Vaccination Institute was manufacturing a smallpox vaccine using a poxvirus called vaccinia. These were the days before smallpox was eradicated, and mass vaccine supplies were needed—but the vaccine tended to have harsh side effects. A senior official at the institute, pondering this problem, believed the strain of the virus deposited at another institute in Ankara was safer. He also thought that “passaging” vaccinia—or growing it in cells, and then transferring it to fresh cells every few days—could make the virus even more safe.
At the official’s direction, another institute scientist named Dr. Anton Mayr retrieved the vaccinia sample from Ankara and began the passaging process, continuing the work even as he took a new role at the University of Munich. After more than 500 passages, the virus weakened considerably: It produced less harsh side effects and was virtually unable to replicate in human cells. It would be called “Modified Vaccinia Ankara,” or MVA.
MVA initially belonged to the public. In the 1970s, the Bavarian government filed a patent and began pumping out MVA passaged 571 times as part of a smallpox eradication campaign. The MVA-571 vaccine was administered as the first dose, followed by a second dose of the conventional vaccine. Doses were safely deployed to more than 120,000 people until the smallpox vaccination program ended in Germany. (The virus was declared eradicated by the World Health Organization in 1980, though the U.S. and Russia still have samples.)
After containing smallpox, public scientists raced to find new applications for MVA. A graduate student of Dr. Anton Mayr, Dr. Gerd Sutter, passaged MVA further and developed a new strain. Dr. Sutter joined the U.S. National Institutes of Health in 1990. There, he made another important discovery: Beyond its use as a smallpox vaccine, MVA could also serve as a viral vector to target other diseases.
Bavarian Nordic now controls how much vaccine is produced, where it is produced, for whom, and at what price.
That’s where Bavarian Nordic comes in. Founded in 1994, the company was interested in targeting other diseases. By 1996, the company was working with Dr. Sutter, and also entered into a secret agreement with Dr. Mayr. Bavarian Nordic was given the “exclusive and sole access to MVA vaccine stock and MVA viral stock in the possession” of Dr. Mayr, who retained the ability to share MVA for research purposes. In 1998, the company said it was working on a cancer treatment using the virus developed by Dr. Sutter.
Bavarian Nordic claims it then further passaged MVA, finally producing Modified Vaccinia Ankara-Bavarian Nordic (“MVA-BN”)—or what is now called Jynneos. MVA-BN is “derived from Anton Mayr’s seed virus” but has “superior characteristics compared to other MVA strains,” according to the company. (One Bavarian Nordic–funded study found that MVA-BN did not replicate at all in some human cells or caused deaths among severely immunocompromised mice, unlike other strains of MVA. But the clinical significance of this finding remains unclear.)
Despite its initial interest in targeting other diseases, after inquiries by several governments, Bavarian Nordic began developing MVA-BN as a stand-alone smallpox vaccine. “MVA had already been used as a pre-vaccine in the 1970s, so the assumption was that MVA-BN would be effective,” the company said.
The September 11 and anthrax attacks led to a new sense of urgency. The U.S. was gripped by fears about bioterrorism. Topping the list was the release of the smallpox virus—one of the deadliest pathogens in human history. Shortly after 9/11, Anthony Fauci and the NIH met with Bavarian Nordic. The NIH sponsored a regulatory application with Bavarian Nordic and, in 2003, the agency formally began bankrolling the development of MVA-BN for smallpox. Once again, it was public money pushing this work forward—though through a private intermediary.
The move raised some eyebrows. “Agency Chief Spurs Bioterror Research—and Controversy,” blared the headline of a Wall Street Journal article. “I’m not sure Tony should be investing. His experience in products and manufacturing is very limited. Maybe they ought to pay more attention to the invisible hand,” said one venture capitalist.
But the agencies persisted. The U.S. government—primarily through the NIH and Biomedical Advanced Research and Development Authority (BARDA)—funded clinical studies, dose purchases, new formulation development, and even the qualification of a new production facility.
Public records show the U.S. has poured $1.97 billion since 2003 into Jynneos. Millions more was likely spent supporting independent clinical studies run by the NIH and CDC. In total, U.S. support for the vaccine likely exceeds $2 billion, according to my research at Public Citizen.
Aside from financing, the U.S. government has carried out its own research directly. In 2015, Army scientists, subsidized indirectly by BARDA, ran a pivotal clinical trial comparing the immune response from Jynneos to a traditional smallpox vaccine in U.S. service members stationed in South Korea. It was also U.S. officials who first raised the possibility of getting Jynneos authorized for monkeypox, because the two viruses are similar. Bavarian Nordic did not initially request such regulatory authorization.
When Jynneos was finally approved for both smallpox and monkeypox, the head of Bavarian Nordic thanked the U.S. government: “Jynneos is the culmination of a fifteen-year partnership that started with a call from the NIH for a safer smallpox vaccine, successfully transitioned to BARDA and was delivered to the Strategic National Stockpile for use in an emergency.” U.S. officials are more forthcoming about their contribution. Dawn O’Connell, assistant secretary for preparedness and response at the Department of Health and Human Services, told reporters: “The world has Jynneos because we invested in it.” In a sense, it was a remarkable success—a rebuke to those who thought that public-health agencies could not develop drugs.
Yet the debacle of the monkeypox vaccine rollout nonetheless underscores the limits of this approach. Bavarian Nordic now controls how much vaccine is produced, where it is produced, for whom, and at what price. The profiteering is bad enough. But consider also the fact that the company threatened to cancel orders from the U.S. government even after its foundational support. Or that the company closed its factory last year because it wanted to increase the capacity to produce another vaccine. As the new outbreak raged, for several months, no new bulk vaccine was produced at all. Instead, the world was reliant on stockpiled bulk that could be converted into finished doses. As one former CDC official responsible for the Strategic National Stockpile recently asked on Twitter, “Who is in charge? … Why does [the] U.S. not hold [a] license for $2B investment?”
The problem, it turns out, was not empowering public-health agencies too much, but too little. A whole-of-government approach was organized only to prop up Bavarian Nordic, without asking for virtually anything in return. A better approach could have recognized the centrality of public power to public health. At a minimum, we might require up-front agreements for publicly funded companies to set reasonable prices and to license technology to help expand supply. The U.S. could also return to the model used in Bavaria that helped bring MVA to the world many decades ago: build a wholly public vaccine laboratory, working with academic partners, to develop and produce vaccines.
