Every country wants a covid-19 vaccine. Who will get it first?

The Chinese company Sinovac Biotech developed an experimental vaccine for SARS back in 2004. That disease went away after killing just 800 people, and the project was shelved. But it meant that when the new coronavirus, SARS-CoV-2, exploded in China last January, the company had a road map for what to do next. Four months later, it published evidence that it could protect monkeys against the disease using a simple vaccine made from killed virus.

By then, though, China had a different problem: not enough covid-19. Its draconian lockdown measures had quashed the virus at home so effectively that doctors couldn't find patients to fully test their vaccine on. The US had plenty of infections, but tensions between the countries meant no Chinese vaccine for covid-19 will ever be tested on US soil.

So in June Sinovac struck a deal with a Brazilian vaccine center, the Butantan Institute in Sao Paulo, to run a large trial there on about 9,000 health-care workers. For Brazil, battered by covid-19, the study comes with a clear quid pro quo. Butantan will pay for the trial and recruit volunteers; in exchange, Sinovac has promised to supply Brazil with 60 million vaccine doses and to let it manufacture further supplies as well.

Brazil can do that because, since the 1980s, it has carefully protected its ability to study, manufacture, and bottle vaccines at Butantan and at a second center near Rio de Janeiro. The national immunization program of Brazil has self-sufficiency as a goal," says Ricardo Palacios, the Butantan infectious-disease doctor who is running the study.

People in every country in the world will soon be clamoring for covid-19 vaccines. The US, through a government initiative called Operation Warp Speed, has already spent more than $5 billion to get drug makers to manufacture vaccines on its soil. China has a portfolio of its own candidates and has ramped up investment in biomanufacturing. But other countries, particularly in Europe, over the years have sold off or shuttered government manufacturing centers, let national expertise disappear, lost interest, or come to rely on neighbors to make and bottle vaccines.

An ample supply of a covid vaccine could become a coin of geopolitical power, as oil and nuclear weapons are now. Governments will be counting on it to allow them to reopen economies and assure political stability. Alliances are already shifting, with leverage going to countries that can create vaccines, test them, manufacture bulk ingredients, and perform the fill and finish" bottling. The rest of the world apprehensively watches, fearful of being left defenseless against the deadly pandemic.

America first

The race toward covid vaccines has moved with unprecedented speed. As of July, several candidates, including Sinovac's, had been shown to protect monkeys and proved safe in initial tests on people; the next phase of clinical trials tests whether they work at conferring immunity. Experts say we'll need several vaccines, not just one, and it's likely that supplies will be sharply limited at first. That's why there is already unprecedented competition among nations to secure the shots.

Behind the scenes, bartering for access to vaccines has already started, and everything is on the table, says Pierre Morgon, a biotech consultant who has been working with CanSino, another Chinese maker of covid vaccines. You get into the dark world of horse trading," he says. During the H1N1 flu pandemic in 2009, when he was with the French drug company Sanofi, Morgon says, diplomats in Paris selected which countries should get priority supplies. The list included nations that supply commodities France depends on: gas, oil, and uranium. It was not even thinly veiled," says Morgon.

And it won't only be states vying for access, but also companies, individuals, even criminal gangs ready to hijack a refrigerator truck. During the H1N1 outbreak, France posted its gendarmerie at the gates of the Sanofi factory. When you have something in short supply and high demand, it has a street value," says Morgon. Just look at the masks, with people reselling them at massive multiples." Western intelligence services allege that Russia has already deployed a team of hackers known as Cozy Bear to extract vaccine secrets from UK and US servers.

In the US, the Trump administration has the aim of securing 300 million doses of a safe, effective vaccine by January, something it has sought to guarantee through pre-purchase" agreements. When it announced a $1.6 billion payment to Novavax, a biotech company with no vaccines on the market (the money is for manufacturing one), the Department of Health and Human Services specified that the federal government will own the 100 million doses of investigational vaccine" expected to result from the contracts.

The implication: it's for Americans first.

A similarly risky US advance purchase deal with Paris-based Sanofi-risky because no vaccine is guaranteed to work-created a diplomatic breach with France. Sanofi's CEO, Paul Hudson, said the US has the right to the largest preorder because it's invested in taking the risk." French officials called the explanation unacceptable," saying a vaccine should be a global public good" and that equal access for everyone to the vaccine is not negotiable." Similarly, in June Doctors Without Borders, the international nongovernment medical group, put out a fiery statement against nationalist stockpiling measures," saying that global solidarity should be paramount."

The nonprofit Gavi vaccine alliance, which is based in Geneva and buys vaccines for poor countries, is raising $2 billion to make its own pre-purchase agreements for covid-19 immunizations so that everyone will get supplies at the same time. We saw a danger that vaccines would get snapped up by wealthy countries, and there would be no vaccines for the rest of the world," says Gavi CEO Seth Berkley.

I understand national governments trying to protect their citizens ... but the issue is that you are not safe unless everyone is safe," he says. If epidemics are raging in the rest of the world, you can't go back to normal, you can't travel, you can't do tourism-you are not going to get the reprieve from the economic crisis."

Better than trying to immunize everyone in a few countries first, says Berkley, would be to distribute the initial doses to vaccinate a portion of each country's population. If there are 2 billion doses available in 2021, as he anticipates, every country could vaccinate 20% of its people, including health workers, those at higher risk, and potential superspreaders" like prisoners, people in refugee camps, and workers at meatpacking plants.

The reality could be a little different, says Clint Hermes, a lawyer at Bass, Berry & Sims, who specializes in vaccine trials. It may not be fair that some countries buy ahead of others, but that is what is likely to happen," says Hermes. I don't think anyone expects the US to send vaccine to Angola before it gets to Arkansas ... The real challenge with equitable access is how to make it work. Ethicists can sit in a room and decide who gets what in what order, but none of that matters unless there is a financing mechanism."

The gamble

For now, there's no proof that any vaccine works, so all the bets involve risk. Early in the pandemic, the US and nonprofit funders heavily backed advanced technologies that were quick to generate candidates but have never yet led to an approved vaccine or been produced at scale. These include the RNA vaccine being developed by Moderna Pharmaceuticals, and a DNA injection from Inovio Pharmaceuticals; both try to directly deliver genetic information about the virus into a person's cells. Since then, the US has also funded Johnson & Johnson, which uses a more conventional approach.

Morgon compares it to a race in which there are an ostrich, a horse, and a dog" at the starting gate. You want to lay a bet on each kind of animal," he says.

In Brazil, far-right president Jair Bolsonaro, sometimes called the Tropical Trump," has scoffed that the virus is a mere cold, fired his health minister, and claimed that a malaria drug, chloroquine, cured him when he contracted covid-19 in July. Instead of going through the federal government, the trial in Brazil of the Chinese vaccine is being financed by Joao Doria, governor of the country's richest state, Sao Paulo, and a rival of Bolsonaro's who has his eyes on the presidential palace.

Sinovac's vaccine uses a tried-and-true approach-virus that is chemically inactivated, or killed-and Palacios says Brazil will be equipped to manufacture it locally once a production line is retrofitted. Berkley therefore sees a tortoise and hare" situation in which conventional approaches may reach the market first or become more widespread.

Despite the intense focus on a vaccine, some worry it's the wrong priority. William Haseltine, a onetime HIV researcher and biotech entrepreneur, thinks more effort should be spent on antiviral drugs-the strategy that eventually brought AIDS under control. That, he says, would buy time to create a vaccine whose safety is fully understood before trying to inoculate billions of people.

This is not an ordinary situation for vaccine development, because there is such political and economic pressure to find a solution to the problem," says Haseltine. If we launch a vaccine that is not fully vetted for safety, and has nasty side effects, there will be hell to pay for vaccines for years, which would cost hundreds of millions of lives."

Science on trial

This summer and fall, companies and researchers should start getting data on whether the vaccines under development really protect people against infection by the coronavirus, or at least from its worst effects.

The US has redirected a federally funded network based at the Fred Hutchinson Cancer Research Center in Seattle, which had been testing HIV vaccines, to instead gather evidence on five covid-19 vaccines in big trials of 30,000 people each. Chinese companies, without enough cases at home, are running studies in Canada, Brazil, and elsewhere.

NICOLaS ORTEGA

Lawrence Corey, a virologist from Fred Hutchinson who was tapped by Warp Speed in July to head the US trials (see Q+A, page 31), says the vaccine hunt is moving quickly because scientists have been planning for success." Rather than wait for final proof that a shot is effective, for example, companies are using US government funds to scale up manufacturing now. The ramp-up for the studies is extremely fast-much faster than for any trial that I have ever been involved in," says Boris Juelg, a doctor at Harvard who is among those who have switched their efforts to covid-19 trials.

One danger now is that governments will push to release a vaccine prematurely. In the US, for instance, the Food and Drug Administration approved chloroquine for treating covid-19, only to reverse itself weeks later after it became plain the drug didn't work. By then, India had blocked exports of raw ingredients, the US had spent millions on useless stockpiles, and Brazil's president had ordered the army to manufacture vast supplies of the drug. I expect the vaccines to be less of a circus, and a lot more cutthroat," says Hermes, the vaccine lawyer.

One danger now is that governments will push to release a vaccine prematurely.

Another worry is that evidence for or against a vaccine could get twisted. Already, a sizable part of the population suspects vaccines are part of a plot. US polls carried out this summer show about a quarter of respondents say they would refuse a coronavirus vaccine.

The efforts risk getting caught up in politics, too. In July, President Trump said the US would exit the World Health Organization, a body that has a major role in setting common standards, such as which type of mouse to test vaccines on. The White House has also attacked its own top virologist, Anthony Fauci, whose institute funds the testing of vaccines.

Since the start of the pandemic, fast sharing of information has been a key weapon against the virus. It was the publication of the germ's genetic sequence in January, by Chinese scientists, that kicked off the vaccine race. After that, European doctors flooded academic journals with descriptions of cases and tricks they had learned for managing severe illness. With vaccines, whether they originate in China, the US, or the UK, sharing data will be crucial so that researchers can compare notes.

They may, for example, learn how to tell whether someone has developed immunity to the virus by measuring the level of antibodies or certain immune cells in the blood. If they do, the third or fourth vaccine to reach the market might get approval based on biomarkers alone. There will be no need to wait a year-as in a typical vaccine trial-to find out what proportion of people who were given the vaccine subsequently got sick.

To Corey, at the Fred Hutchinson, the involvement of large multinationals like AstraZeneca and Merck is likely to act as a bulwark against the politicization of vaccine research and supplies. During the Ebola crisis, the winning vaccine was created in Canada, sold to Merck, funded by the US, and tested in Guinea, under the coordination of the World Health Organization. It is now manufactured in Germany. Says Berkley, Try to make that nationalistic-how would you even define that?"