By Marco Evers, Georg Fahrion, Veronika Hackenbroch, Laura Höflinger, Kerstin Kullmann, Raniah Salloum, Alexander Sarovic, Cornelia Schmergal and Alexander Smoltczyk
They speak almost reverently about it in the laboratories and meeting rooms of Curevac. The call it “the candidate.” It may not have a name yet, but it does exist. It apparently has all the right qualities and exhibits promising values. It just needs a bit more time.
“We call it ‘the candidate,’ because CVnCoV isn’t so easy to pronounce,” says Florian von der Mülbe, the man responsible for production on the Curevac board. The biotech firm, which is based in the southern German city of Tübingen, has just moved into its new office buildings on the hills above the university town. You can see the ridges of the Swabian Alb mountains from the window, and moving boxes still line the hallways. Still, there’s no time for dilly-dallying. The world is waiting with growing apprehension, with many fearing that a second wave of the coronavirus pandemic is imminent — and that the next wave could be deadlier than the first. The only reliable hope for billions of people around the world that a vaccine will be developed soon.
“We have invested a large share of our resources in the development of a corona vaccine,” says von der Mülbe, who then goes on to share the questions his neighbors and friends have been asking him for weeks: When will your vaccine be ready? Where’s this candidate?
The candidate was created in part in room C.3.111, “RNA Optimization & Supply,” developed in a robotically automated laboratory workstation that is roughly the size of a refrigerator. A picture of Cinderella is affixed to it. The company says it already has a few million doses of the trial vaccine ready and the first clinical tests on 168 people are expected to start soon.
Germany’s 300-Million-Euro Gambit
The German government is hoping that the vaccine being developed here can be deployed around the world to halt the coronavirus. Berlin announced this week that it would invest 300 million euros in Curevac, putting 23 percent of the company under state ownership, with the government saying it is taking the step to prevent the company from moving abroad if it goes through with a planned IPO on the stock exchange in New York in July.
The German government wants Curevac to stay in Germany because of the ongoing presence of the virus. The number of new infections may be low at the moment, but just as China is currently experiencing a new outbreak, there’s a risk that the disease will flare up again in Germany. Many fear there will be a second wave of infections and no one knows right now what effect the loosening of the lockdowns in Europe will have. The only thing that can really make a decisive difference is a vaccine.
Production manager von der Mülbe spends 10 to 12 hours a day on the phone arranging meetings with supervisory authorities and negotiating with suppliers. The candidate isn’t his only problem. As with all of the company’s competitors, Curevac is already facing the threat of bottlenecks.
The mini vials made of special medical glass that vaccines are transported in are in short supply around the world. Demand is enormous, but the number of suppliers is limited. It’s almost reminiscent of the recent run on toilet paper around the world. In the case of the mini vials, though, this is just the beginning. Hypodermic needles are also becoming scarce around the world and existing manufacturing can’t easily be scaled up.
Indeed, developing the actual vaccine is only one of the steps necessary toward making it widely available. It will also have to be produced, distributed and administered in quantities that are difficult to fathom – and all of that will have to happen very quickly. But how?
Once a functioning vaccine, or several different vaccines, for the COVID-19 virus is approved worldwide, around 6 billion doses will be necessary. Or twice that if boosters are required to achieve immunity.
You don’t have to be a pessimist to see that it won’t be possible to meet that demand immediately. Even in the best-case scenario, it may take years before enough vaccines can be produced and delivered.
And that means that the question as to when a vaccine will be ready must be followed up with an even more challenging query: Who gets supplies of the life-saving substance first? And who gets to decide? The answers will determine life and death. And the prosperity or poverty of entire nations will also be at stake.
The mysterious rise of the American biotech pioneer Moderna illustrates the problem at hand. The small Boston-based vaccine company hasn’t launched a single product in its close to 10-year history, but the company is currently worth more than $23 billion on the stock exchange.
When the company recently reported initial success with its experimental mRNA-1273 vaccine in only eight volunteers, it caused not only the company’s share price to spike, but it also boosted the Down Jones index by almost 4 percent and Germany’s DAX index by more than 5 percent. It’s no less than the future of the global economy that is currently being decided in the laboratories of the vaccine manufacturers – and also who will have a share of the wealth and who will not.
The U.S. vs. China and the EU
Rivals in the U.S. and China, in particular, are engaging in a multibillion-dollar race to develop the first vaccine. Both U.S. President Donald Trump and Chinese President Xi Jinping are well aware that whoever gets their hands on it first will be the first to emerge from the crisis, perhaps even stronger than before.
Developing the vaccine means much more than just technological prestige for the two global powers. It could also become a means for applying political pressure, a power factor not unlike the politics of oil. The question of who has this essential resource could put an end to old alliances and create new ones.
Trump is also well aware of the powerful battalions he has at his disposal to send into the battle for the vaccine. America is home to the best laboratories and the most powerful pharmaceutical industry in the world. With Pfizer, Johnson & Johnson and Merck & Co., all of which had revenues of more than 40 billion dollars in 2019, three of the six top-selling companies in the industry are American. Four of the world’s top five biotech companies are American, including Amgen (market value: 119 billion euros) and Gilead Sciences (83 billion euros).
But it’s also clear that the powerful U.S. will not be able to defeat the coronavirus on its own. It can only do so with China’s help, because no matter what “Big Pharma” wants to produce, the active pharmaceutical ingredients, the basic ingredients of almost every drug, have been mostly manufactured in China and India for the past decade.
The crisis caused by the coronavirus provides China will the opportunity to finally catch up with America in the strategically important biotech sector. China doesn’t have any pharmaceutical companies yet that are known worldwide for their strength in innovation, but SARS-CoV-2 could change that.
The Coming Conflict
No politician, no society, no state, and neither the European Union nor the United Nations nor the World Health Organization (WHO) is really prepared for the conflicts over distribution and fairness that will arise internationally and within each country from vaccine scarcity.
It seems safe to assume that the rich, the powerful and the selfish will prevail as usual. Unless, that is, the parties involved succeed together in laying down ground rules on who has access to the vaccine, when and why.
Only five and a half months ago, the SARS-CoV-2 pathogen was completely unknown. Today, thousands of researchers in more than 12 countries are working on over 130 vaccine development programs. Around a dozen pharmaceutical companies and government research institutions have already begun conducting human trials in the U.S. and China, but also in Britain, Australia and in Germany.
The Americans have already ordered 300 million doses of a trial vaccine. The Europeans have ordered 400 million.
Never before have scientists, pharmaceutical companies, startups, funders and regulators achieved so much so quickly, although it is still completely uncertain when, how and even if any of these projects will bear fruit.
It’s also still unknown how long the hoped-for immunity will last after vaccination. Experience with other coronaviruses suggests that the vaccine might have to be administered every one, two or three years. This would increase the risk of global scarcity by orders of magnitude and also exacerbate conflicts over distribution.
The development of vaccines has always been a long, exorbitantly expensive and, above all, high-risk process. The substances researchers pin their hopes on can turn out to be nonstarters or even deadly in clinical tests. One Dutch study found that only around 6 percent of all vaccine projects have ever made it to the market.
By joining forces, the countries conducting the research could minimize the risk of eventually being left without a vaccine. But they’re finding it chronically difficult to work together – and this isn’t only a product of the recent escalation in the dispute between Washington and Beijing.
Showing Their Selfish Sides
When pandemics strike entire populations, even friendly states can show their selfish side. When SARS-CoV-2 began spreading around the world in March, dozens of countries closed their borders and banned the export of medicines, protective clothing, disinfectants and ventilators. France even seized masks that were intended for Spain and Italy.
When worse came to worst, there was often no trace of global solidarity, of respect for supply chains or existing contracts. There’s no reason to believe that countries will act any differently when it comes to the vaccine. In March, the news broke that the U.S. had sought to obtain the exclusive rights to the vaccine being developed by Curevac. The Tübingen-based company denied the report, but the incident shows that such brazen attempts aren’t completely out of the realm of possibility.
When WHO declared the swine flu a pandemic in 2009, experts also predicted that millions of people could lose their lives (which ultimately didn’t happen). The first new vaccine for the H1N1 virus became available after only seven months – and wealthy countries immediately bought up the global supplies.
The U.S. alone – which was much more engaged with the world under President Barack Obama at the time – signed contracts for 600 million doses of the vaccine. Poor countries and emerging economies, meanwhile, were left empty-handed for quite some time. Many experts agree that the goal this time around should be that of preventing a repeat.
Three Centers of Power
There are essentially three major centers of power for vaccine research around the world: the U.S., China and the EU. And there is blatant distrust and fierce competition between these parties. Currently, the situation situation looks as follows:
In the U.S., the bombastically named Operation Warp Speed follows the Trumpian logic of “America First”: Billions of dollars are raining down on American pharmaceutical companies, and the U.S. military and numerous research institutes are involved in the endeavor. The goal is to develop an effective and safe vaccine by the beginning of 2021, with Americans getting priority access to the substance. To save time, many of the necessary steps in the process – clinical tests, for example – are taking place in parallel rather than one after the other, as is usually the case. The aim is to radically reduce the amount of time it takes to develop a vaccine, from a normal period of several years to just a few months. Many experts have criticized the approach as being too hasty.
China started work developing a vaccine earlier and is likely more advanced at this point than any other country. Beijing is hoping to begin production of a vaccine by the end of the year. Two highly secure factories – one in Beijing and another in Wuhan – could initially produce 200 million doses of the vaccine a year using deactivated coronaviruses. The Chinese vaccine projects are subject to state control, and the military is also involved. The country’s vaccine development is so secretive that no other country can really assess how risky or successful products will ultimately be.
The EU’s own coordinated vaccine research effort is born out of the realization that Europe won’t be able to rely on the U.S. or China in this crisis. Many EU countries are pushing forward to expand their vaccine production capacities.
Trump, for his part, had long been an anti-vaxxer. He has claimed, for example, that vaccines cause autism in children, which isn’t true. But now he wants a COVID-19 vaccine, whatever the cost and as fast as possible.
The operation in the U.S. is being led by former pharmaceutical executive Moncef Slaoui and four-star General Gustave Perna of the U.S. Army. A budget of $10 billion has been initially made available. The basic rules are simple: Whatever happens, American companies have priority. Cooperation with China is out of the question, as is partnering with the EU, WHO or other international bodies.
At the same time, the U.S. Department of Health and Human Services is spending considerable money in an effort to secure vaccines elsewhere. It has agreed to pay the British-Swedish pharmaceutical company AstraZeneca more than a billion dollars for 300 million doses of a vaccine developed for testing in Oxford, England, which will be available in January. That’s a dose for almost every U.S. citizen. Trump hopes to receive the first several million doses by October, in time for the election.
Trump has compared Operation Warp Speed to the legendary Manhattan Project, which developed the nuclear bomb in the 1940s. The comparison is revealing. For him, coming in first is crucial. “Winning matters,” says Defense Secretary Mark Esper. At the same time, it would be easy enough for the U.S. to lose, because Operation Warp Speed is focusing its considerable resources on only five vaccine candidates, all of which are extremely ambitious from a technological point of view. What happens if they all fail?
Trump’s intention to make the vaccine available to Americans first, no matter what their risk of infection is, testifies to a kind of nationalist thinking that is so menacing in this crisis. Few people are as aware of that as Seth Berkley, the CEO of the Geneva-based vaccine alliance Gavi, which provides vaccine for developing countries. “The pandemic is global,” says the epidemiologist. “We need to find global solutions.”
On behalf of Gavi, Berkley has recently collected the unimaginable sum of $8 billion in donations – and he has already spent some of it. He placed a huge order with AstraZeneca for 300 million glass vials for vaccine delivery, all of them earmarked for developing and emerging countries. Delivery should commence toward the end of the year.
“This is a difficult challenge for the world,” says Berkley. “We won’t be able to put an end to the epidemic anywhere if we don’t end it everywhere.” For as long as the global population hasn’t built up sufficient immunity, he says, the disease can reappear anywhere in a second or third wave, perhaps even more dangerous than it is now.
If countries already begin competing for vaccines and drugs, agrees the U.S. health expert Thomas Bollyky, “then there will only be losers.” Even just a well-coordinated global campaign can help, as long as it makes the best research and results available around the world.
Several such initiatives have launched in the shadow of the U.S.-China confrontation. Under the auspices of the WHO, with support from the EU and several other countries, an ACT-accelerator (ACT stands for “access to COVID-19 tools”) was launched in Geneva in late April. It is essentially a consortium including Gavi and many other initiatives.
At the donor conference in early May, 7.4 billion euros was raised for the accelerator, with 4 billion of that earmarked for vaccine development. The plan calls for much more money than that to be made available to participating countries in the future.
Germany has thus far pledged 525 million euros, the European Commission a billion, Canada 550 million euros and Australia has promised 200 million euros. There has been no support forthcoming from the U.S., Brazil, Russia or India, the latter of which will likely play a key role in the battle against the coronavirus due to its vaccine production capacities.
“Available to All of Humanity”
The tests, therapeutics and vaccines produced by the accelerator are to be treated as the property of the global community. Depending on the financial resources available to a given country, the products developed could be supplied for free or paid for via loans. “Once there is a good vaccine, it must be made available to all of humanity, paid for by wealthy countries,” Karl Lauterbach, a health expert with the center-left Social Democrats (SPD) in Germany, recently tweeted.
Another participant in the accelerator is CEPI, the second alliance that is investing heavily in the search for a vaccine. Other participants include the Global Fund, the British health foundation Wellcome Trust and the Bill & Melinda Gates Foundation.
At the World Health Assembly in mid-May, the WHO passed a resolution that could be interpreted as a challenge directed at the U.S. and China. It includes a demand that all countries have equal access to vaccines and medicines and also clearly states that international patent rights may be restricted for that purpose. Should the need arise, countries would be allowed to ignore rules for the protection of intellectual property and clone drugs even without a license. The U.S. was the only country in the world to voice criticism of this passage.
“It is noteworthy that over 140 member states explicitly supported this resolution, including those in which a vaccine may actually be developed,” says Olaf Wientzek of the Geneva offices of Germany’s Konrad Adenauer Foundation, a think tank aligned with Chanceller Angela Merkel’s conservative Christian Democrats.
The resolution is a success for the Europeans since they were the driving force behind it. Even Australia and Japan, both of which have recently been quite critical of the WHO, joined the initiative. Given the vast consensus, China sought to improve its image and announced a pledge of billions more dollars for the global fight against the virus.
Chinese President Xi also promised that vaccines developed in China would be made available as a “global public good,” particularly to poorer countries. He did not, however, comment further on what that might actually mean.
“By definition, a global public good” would mean “that everybody should have access to the vaccine,” says Yanzhong Huang, a senior fellow for global health at the U.S. think tank Council on Foreign Relations. But because that is essentially a practical impossibility, the pledge cannot be taken at face value, he believes. “It is unrealistic to expect China to have the vaccines provided for free to everybody on this planet.”
It is, however, conceivable that China could share the methods and data pertaining to vaccine production with other countries. Developing countries that don’t have laboratories to produce the vaccine themselves could be supplied by others that do. The same likely applies to participants in China’s Belt and Road Initiative. Even if China won’t likely be able to demonstrate quite as much generosity as Xi’s words might suggest, Beijing has staked out a position that is far less self-centered than the naked selfishness of the U.S.
The internationally minded accelerator is a project of hope. “This is the best strategy to get a vaccine, drugs, diagnostics and better public health,” says Jeremy Farrar, head of Wellcome Trust.
So, will the world really be able to confront this global catastrophe with a community approach? Yes and no. Important agreements have been reached and fundamental principles for greater fairness have been established, and yet not everybody will be in the same boat in the future. It remains to be seen how much the pledges from wealthy countries will ultimately be worth. The political forces that will be exerted due to the scarcity of the vaccine will be intense.
The German government is supporting international efforts to develop a vaccine with both money and rhetoric, both of which is a welcome relief from the bombast coming from the U.S. Berlin is pursuing several strategies at the same time. And demonstrating solidarity is an important aspect, but not at the price of placing Germany at a disadvantage.
Health Minister Jens Spahn has pushed his European counterparts to establish a response to U.S. unilateralism. The result has been an alliance of Germany, France, the Netherlands and Italy. And they, too, have placed an initial order with AstraZeneca for up to 400 million doses of the experimental vaccine being developed in Oxford. Delivery is scheduled to start in late 2020.
Negotiations with additional producers for the purchase of specific amounts are currently ongoing. Each of the four members of the European vaccine alliance is to pay a quarter of the cost, but the vaccine is to be delivered across the entire EU. The doses are to be divvied up according to size of population, Spahn and his three alliance counterparts wrote. The more inhabitants a country has, the more doses it will get.
The Highest Bidder?
In addition to community efforts, though, some countries are also pursuing a solo approach. The French company Sanofi – which was heavily criticized recently for briefly considering the approach of initially only selling vaccines to the U.S. – is planning to build a new vaccine factory and state-of-the-art research laboratory near Lyon. Neither Paris nor Berlin want to be as dependent on foreign vaccines and medicines as they have been thus far. Moving pharmaceutical production sites back to Europe will be an important priority when Germany takes over the rotating European Council presidency on July 1.
Germany has also made other preparations. On May 11, the “Corona Cabinet” in Berlin passed a purely national program in which the Education and Research Ministry will provide 750 million euros to support vaccine producers in Germany and secure production capacity at German companies like Biontech in Mainz or Curevac. The plan calls for these facilities in Germany to be rapidly converted if, for example, the mRNA vaccine from Curevac proves ineffective but the one from the U.S. competitor Moderna succeeds. The German government’s investment in Curevac is also intended to guarantee exclusive access to a vaccine.
Article 2 of the German constitution holds that the state is responsible for protecting the health of all people living in the country. But if a pharmaceutical firm in southern Germany, for example, was to produce a vaccine that is desperately needed around the world, who would it go to? The highest bidder or those in greatest need?
CEPI Chair Jane Halton has warned of what she refers to as “vaccine nationalism,” a refusal on the part of some countries to share the scarce commodity with other countries. As soon as an effective product comes available, Halton says, political pressure will develop in many countries to ensure that the national population is helped first.
The German government says it will provide 750 million euros in support to companies in the development and production of a COVID-19 vaccine in Germany.
Infectiologist Farrar from the Wellcome Trust has already prepared a solution for this dilemma. Vaccine factories, he says, should be located in countries that are technically advanced, but which have a low population, such as Singapore, Denmark or New Zealand. Such countries could quickly take care of their own needs and could then work on behalf of the rest of the world.
The fundamental problem with the idealistic concept of global public good, however, would still exist. The more countries that must be supplied with the vaccine, the scarcer it will be for all. That would mean that local outbreaks would last longer, and economies would take longer to recover.
It is an “insoluble paradox,” says the London-based vaccine expert David Salisbury of the think tank Chatham House. Prior to his current position, Salisbury worked for the British government and was also part of high-level panels at the WHO. He is fully aware of the destructive forces such a situation can produce. “The more equitable you become with access to supply, the less efficient the ability that you will have to protect your population and stop transmission,” he says.
Salisbury has no illusions. “Much of the outcome will be: Who has got a contract with pharmaceutical manufacturers? And then what decisions the manufacturers come to about how they will prioritize their customers?” In cases of conflict, he fears, the countries in which the production facilities are located may simply pass a ban on the export of vaccines.
The U.S., Salisbury says, has already indicated that it would actively make use of such bans. He doesn’t even rule out the EU adopting a “Europe first” policy. The 27 EU member states could act as a bloc for the joint procurement of vaccines. “So would the EU come to a view that an EU producer should serve the European joint procurement first before vaccine leaves the EU?” he wonders.
His conclusion is clear. The altruism of even well-meaning countries is limited. “The depths of your pockets defines how quickly you get vaccine,” he says.
Germany has deep pockets and will likely be able to secure significant quantities of a vaccine. How, though, will it be distributed?
It seems likely that health care workers would be the first to receive the vaccine so that medical practices, hospitals and care facilities can continue operations. This approach has a broad consensus in Berlin at the moment. People who belong to high-risk groups would also be vaccinated early on. But then?
The article you are reading originally appeared in German in issue 26/2020 (June 20, 2020) of DER SPIEGEL.
All those who yell loud enough and are willing to pay a high price? Police and firefighters? Teachers? People who work in vital industries like automobile manufacturing or workers in places that have been hit hard by the virus, like slaughterhouses?
Tobias Witte, 34, is a medical lawyer in the city of Münster and is well prepared for the legal questions raised by the pandemic. From 2011 to 2013, he wrote his Ph.D. thesis, the first run of which is now sold out. It is called: “Law and Equitableness in a Pandemic: Stockpiling, Distribution and Pricing of Scarce Medicines in the Case of an Epidemic Outbreak.”
For Witte, it is clear that when decisions are made about who receives a vaccine first and who is further down the list, it should not be arbitrary and factors such as power or market power cannot be decisive. Law must be applied. “We badly need a federal law on vaccine distribution,” he says. That law must ensure, he adds, that every single action is taken to save as many human lives as possible with the limited number of vaccine doses available.
“Veil of Ambiguity”
Nobody yet knows what kind of characteristics the vaccine will ultimately have. Whether it will be suitable for everyone or how risky it will be. Given such doubts, is it not too early to begin establishing the legal framework for the distribution of the vaccine?
Witte actually believes that this lack of detailed knowledge represents an opportunity. “If I don’t know where I stand in a catastrophe, then I will make decisions that are less self-interested,” he says. Distribution resolutions passed in an atmosphere of uncertainty, he believes, tend to be relatively fair because decision-makers try to do well by everybody. The “veil of ambiguity” is clearly advantageous, the lawyer says.
It is not German parliament, however, that decides on the distribution of scarce goods in the health-care system, particularly when ethically sensitive questions are involved. Health Minister Spahn has commissioned a group of 18 scientists and medical professionals to develop a distribution plan.
The Standing Vaccine Commission (known as STIKO for short) at the Robert Koch Institute is to develop a “risk-oriented prioritization concept” for vaccine distribution, according to a ministry response to a parliamentary inquiry. STIKO has been around for years, deciding which vaccines are necessary for which groups of people – and doctors tend to adhere to their recommendations without the need for cementing them into law.
But will that system withstand the pressures that come along with the COVID-19 pandemic? Or will patients sue their doctors because they were denied the vaccine in favor of a privately insured patient?
Producers, for their part, are preparing for mass production. AstraZeneca has already secured global production capacity of 2 billion vaccine doses of the vaccine from Oxford, despite it not yet having been approved.
The company Serum Institute of India (SII), the world’s largest vaccine producer, is a significant part of the massive production expansion. Currently, SII, located in the city of Pune, produces around 1.5 billion doses of various vaccines per year, including those for diseases such as tetanus, measles, polio and mumps.
Preparing for Future Pandemics
SII head Adar Poonawalla, 39, is planning to begin production of a SARS-CoV-2 vaccine now. By autumn, he hopes to have produced 40 million doses, at which time it will become clear if it is granted approval – or not.
If it is approved, Poonawalla intends to make at least half of the doses available to India, with the rest going to countries that don’t have their own vaccine. If approval is not forthcoming, it will all be discarded.
Poonawalla’s company joined the project at its own risk. In the worst-case scenario, he might lose a few million euros of his multi-billion-euro nest egg. But should everything go well, he’ll be a hero by the end of the year – and have the reputation for being a visionary businessman.
Currently, SII sends most of its exports to Africa, South America and Asia, though Poonawalla has long wanted to expand into the North American and European markets. He views this crisis as an opportunity for the Indian pharmaceuticals industry. “The world has always underestimated our capabilities,” he says.
It is difficult to see a solution for vaccine scarcity without the participation of India. Vaccine producers in the country cover roughly 60 to 70 percent of global demand. And the prices they command are often merely a fraction of those paid in the West.
In this pandemic, many of the pharmaceutical companies have signed cooperation agreements with Western partners, which could elevate them to a new level. Poonawalla has joined forces with the U.S. biotech company Codagenix and the Austrian firm Themis.
SII is also in the process of building a new, extremely flexible factory, with completion expected within three years. It will have a capacity of 700 million doses of vaccine per year – and not just for COVID-19, but for a variety of illnesses. “What the world needs is a pandemic-level facility that can ramp up very quickly in case of a pandemic,” Poonawalla says. And one thing is certain: There will be other pandemics after COVID-19.