After the terrorist attacks of September 11, 2001, fears of a possible bioterrorist attack by viruses or other pathogens also increased in the United States. This prompted the US agency BARDA (Biomedical Advanced Research and Development Authority), which is part of the Ministry of Health, to also promote research in the field of long-forgotten diseases such as smallpox, which have been considered eradicated since 1980.
Among other things, the state authority supported the Danish-German biotech company Bavarian Nordic, which was researching the further development of the already known smallpox vaccine. With success: at the beginning of August, the company, based in Tuborg Havn north of Copenhagen, received approval from the EU Commission for its vaccine against monkeypox and is therefore still the only manufacturer of the preparation worldwide. In order to meet the demand, the group now wants to expand production. The company is currently planning to deliver around four million vaccine doses by the end of 2022 from batches that have been manufactured since May. "We will do everything we can to meet the high demand around the world," said company boss Paul Chaplin.
However, the vaccine is not new. The vaccine was approved in the EU nine years ago – but at that time it was limited to use against conventional smallpox.
Large sums from the USA
Bavarian Nordic, which also maintains a large research facility in Martinsried near Munich, was founded in 1994 and initially focused primarily on cancer research. The history of the development of the vaccine only began when fear of bioterrorism increased in the USA after September 11, says Gerd Sutter in an interview with tagesschau.de. The virologist and professor at the Ludwig Maximilians University in Munich has been researching vaccines and smallpox viruses for more than 30 years.
BARDA threw billions of dollars on the market to develop various vaccines and therapeutics in the early 2000s, Sutter said. They were intended to serve as a countermeasure to bioterrorism. There was nothing comparable anywhere in the world. "The development of Bavarian Nordic's MVA-based smallpox vaccine was funded almost entirely by the United States." The advanced smallpox vaccine is based on a modified form of the old vaccine virus, also known as the vaccinia virus. The adapted form is called Modified Vaccinia Ankara, MVA for short.
Business model that hasn't been very attractive for a long time
In Germany, people played more at risk, says virologist Sutter. The old smallpox vaccine is still stored in sufficient numbers in Germany in the event of an outbreak. For a long time it was not foreseeable whether the vaccine would ever be needed again. For many companies, this was not an attractive business model. "That's also the reason why Bavarian Nordic is currently relatively unrivaled on the market," says Sutter.
In Europe, the monkeypox vaccine from the Danish-German company is called Imvanex. In the US and Canada it is marketed under the brand names Jynneos and Imvamune. However, the vaccine is not the same vaccine that was used against smallpox more than 40 years ago.
It has been known for decades that these old vaccines can cause strong and dangerous side effects, says Sutter. There was an interest in America to develop a more tolerable and modern smallpox vaccine, says Thomas Duschek from Bavarian Nordic tagesschau.de. It was a matter of national security for the US to have enough vaccine in case smallpox broke out again.
Modified vaccine with fewer side effects
According to Hartmut Hengel, virologist at the Freiburg University Hospital and head of the scientific advisory board at the Paul Ehrlich-Ehrlich Institute, the modified form has fewer side effects and "is therefore safer than the traditional vaccine". People who have not yet been vaccinated against smallpox should receive two doses of the vaccine. In the case of people who have already been vaccinated, one can assume that a one-time booster vaccination with Imvanex is sufficient, according to Sutter.
Imvanex from Bavarian Nordic is the only vaccine against monkeypox that has been approved so far – and the demand is increasing. So far, the authorities have reported more than 40,000 confirmed cases from more than 80 countries. According to the Robert Koch Institute (RKI), more than 3,300 people in Germany have contracted the virus. The true number, says Hengel, is probably higher. If you want to catch the spread, you need a coordinated global vaccination strategy. The good news is that there is already a vaccine with a fairly good protective effect.
The EU has so far ordered more than 160,000 doses of the Imvanex vaccine. Most importantly, the US has secured vaccine doses. By next year alone, the United States will receive seven million doses, according to Duschek. Most of them are currently stored by Bavarian Nordic in Denmark and are gradually being shipped from there to the USA. When it comes to storage and transportation, Sutter says there are few concerns at the moment. The smallpox vaccine virus is very long-lasting and very durable. However, the requirements of the current approval must be observed.
The vaccine is stored at a temperature of minus 20 to minus 50 degrees, says Duschek. But if you use the vaccine directly, you can also thaw it. But then it has to be used within days or weeks.
Quantity increase not easily possible
Bavarian Nordic can produce around 30 million doses of the vaccine annually – at least in theory, says Duschek. So far, the company had planned to make 1.5 to two million doses available this year – which is now to be increased to around four million. The manufacturer is also examining the possible use of cans with an expired use-by date.
From the point of view of the Freiburg virologist Hengel, the vaccine cannot easily be produced inexpensively in large quantities. It is a sophisticated vaccine in which an increase in production is not as easy to handle as, for example, with the mRNA vaccines against corona. The vaccine virus has to be grown in cell cultures, and that is much more complex.
Distribution across the federal states
Producing the vaccine from scratch is a sensitive process, says Duschek from Bavarian Nordic. He estimates that it will take between six and twelve months to implement the process in new plants. The biotech company is currently in talks with other contract manufacturers to further increase capacity. From the fall, an American manufacturer should help to fill the vaccine.
In Germany, according to the RKI, the vaccine doses are distributed by the federal states due to the limited availability. The vaccine against monkeypox has already been vaccinated in Brandenburg, Hamburg and Bavaria, and some practices in Berlin are already offering the Imvanex vaccine.
How much the company can make from selling the cans depends on what's being negotiated in each state, the quantity ordered, and the length of the contracts, Showerk says. The company's long-term relationship with the United States means that US pricing differs from that of the EU. There is currently no commercial market, so Duschek. One is currently only negotiating with states about deliveries.
Vaccine also against Ebola
But the biotech company's business isn't just limited to smallpox. In the past, it researched, among other things, a vaccine against rabies. Together with Johnson & Johnson, Bavarian Nordic also developed a vaccine against Ebola. In the corona pandemic, the company, like many other vaccine manufacturers, expanded its business to include corona vaccines.
Briton Paul Chaplin has been at the helm of Bavarian Nordic for eight years. Last year, the biotech company achieved more than 50 percent of its sales with the sale of smallpox and Ebola vaccines – a value that is likely to increase significantly this year. In 2021, the income from the sale of the smallpox vaccine, which went mainly to the USA, was the equivalent of almost 100 million euros.