How to Vaccinate the World

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The giant steel vats used to make most of the world’s vaccines are not easy to come by. They’re highly specialized pieces of equipment; there are only so many of them to go around, and it’s expensive and time-consuming to make more. So when vaccine developers were figuring out how to produce billions of Covid-19 vaccine shots as quickly as possible, they decided to use an alternative: disposable bioreactor bags. At first, it was a win-win. The bags are quicker and cheaper to make than the tanks, and using them can shave precious hours off manufacturing times because they don’t have to be cleaned and sterilized after each use.

But before long, even this innovation became an obstacle in the quest to end the Covid pandemic. First, larger vaccine makers bought up many more bags than they could use, leaving smaller vaccine makers with no recourse and potential manufacturing sites underutilized. Then as the vaccination campaign wore on, supplies began drying up altogether. Only a few companies make the bags, and they have little incentive to ramp up their manufacturing efforts because there’s no telling how long the uptick in demand will last.

“It’s become a huge problem,” Prashant Yadav, a senior fellow at the Center for Global Development, told me in June. “And it’s something that only an actual government can resolve.”

Pharmaceutical companies generally know how to coordinate their global supply chains. They also know how to work together to secure the resources they need to make their products. But when the situation requires changes to national and global policy, world leaders need to step in.

So far, they have not. For all its successes, the race to vaccinate the world against Covid has unfolded like a symphony without a conductor. The corralling of manufacturing sites has been haphazard. The channeling of equipment and ingredients has been messy and at times wasteful. And the flow of vaccines has been recklessly uneven: More than 80 percent of the four billion vaccine doses that had been distributed as of early August went to high- and upper-middle-income countries.

While the United States has bought enough shots to vaccinate its entire population three times over, most low-income nations still don’t have enough to give even first doses to their frontline health workers or older citizens. The People’s Vaccine Alliance estimated in June that at the current pace, it would take 57 years for low-income countries to vaccinate their entire populations. High-income countries will do so within the next six months (hesitancy notwithstanding).

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Credit…Ryan Young for The New York Times

This month, the global vaccine-sharing initiative known as Covax cut its projections by nearly 30 percent, saying it would have available only 1.4 billion doses by the end of this year. (The initiative has delivered just 271 million doses so far.) Later, President Biden reassured Americans that the United States had enough shots on hand to offer boosters to all its residents. The World Health Organization has been pleading with wealthy nations to hold off on boosters — and to forgo some of their planned vaccine purchases — until the rest of the world has a chance to secure more first doses. But if Mr. Biden felt any moral qualms about the United States’ booster ambitions, it didn’t show. “We’re proud to have donated nearly 140 million vaccines,” he said, to “over 90 countries, more than all other countries combined.”

Boosters for the wealthy and scraps for everyone else will neither get us out of this pandemic nor prepare us for the next one. But nearly a year since the first shots were administered, world leaders have yet to put forth a bolder or more comprehensive plan. “Nobody is saying unequivocally, ‘Here is what we need, and here is how we are going to get it,’” said Zain Rizvi, a health law expert at the consumer advocacy nonprofit Public Citizen. “We were promised a war effort, and instead we got a pillow fight.”

Mr. Biden has convened a global Covid-19 summit for Wednesday. Among other things, he is expected to call on world leaders to invest in vaccine making and vaccination and to increase vaccine donations — with the goal of inoculating some 70 percent of the global population by this time next year. Those are welcome steps, but the World Bank, the International Monetary Fund and the W.H.O. set a similar goal months back, and the global vaccine gap has only widened since then. For these latest pronouncements to make a dent in the problem, the summit must be followed, quickly, by concerted action.

While the world dithers, the virus is evolving. Given enough time and enough unvaccinated people, it could mutate its way past our best defenses, potentially sending the world — vaccinated and unvaccinated alike — back to square one. The best hope for preventing that from happening is to make many more vaccines — at least three times as many as the world has so far — and then deploy them as quickly and equitably as possible across the globe.

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To accomplish either of those goals, let alone both of them, we’ll need more than meetings and donations. We’ll need an entirely new global vaccination apparatus.

It’s worth understanding how the existing system failed.

Covax was created so that rich countries and poor ones could pool their resources and use their combined purchasing power to ensure equitable access to Covid vaccines for all countries. The idea was that rich nations would pay a certain amount upfront to secure their own supplies and Covax would use a portion of that money to help lower-income countries buy their shots. All countries would get the same relative portion of doses — enough to vaccinate 20 percent of their populations — but none would be able to choose which shots they received. Covax’s administrators assumed that wealthy nations would also cut side deals but hoped enough would still sign up for their program, even just as an insurance policy, that it would work.

Instead, as the Duke scientist Gavin Yamey told The Lancet, “rich countries behaved worse than anyone’s worst nightmare.” They bypassed Covax — either completely or by slow-walking their financial contributions — cut multiple deals directly with vaccine manufacturers and bought up many more shots than they would need, long before any had been authorized for use. As a result, not only did Covax never amass the purchasing power at the heart of its plan, but also by the time the initiative secured enough funds to start buying shots, it was at the end of a long queue.

In an attempt to lure more high-income countries to its cause, Covax made several concessions in the past year. Rather than enforce its equal access plan, the initiative allowed wealthier nations to buy more shots than poorer ones and to pick which vaccines they would get, while poorer nations have had to take what’s offered. The result was a lose-lose: Covax still does not have enough high-income participants to shore up its purchasing power, and it’s now contractually obligated to reserve one in five of its shots for a small cadre of wealthy countries. As The Lancet notes, Group of 7 countries are entitled to more Covax doses by the end of this year than they have pledged to donate to the initiative.

When Covax failed to deliver, lower-income nations began purchasing doses directly from vaccine makers. But because they lacked the money or negotiating power of wealthier countries, the deals they secured were not as good. For example, they were not able to demand clear delivery timelines or charge companies a penalty if they failed to meet such schedules, a shortcoming that has made it nearly impossible for some countries to plan their vaccine distribution. They were pressed to include expansive liability protections — and in some cases to put their sovereign assets up as collateral against lawsuits.

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Credit…Rodrigo Sura/EPA, via Shutterstock

They were also, in many cases, precluded from banning the export of vaccine products made within their borders. That much is as it should be. “Ideally, you want manufacturing and allocation to be decoupled,” said Mr. Yadav. “That way, shots get made where it makes the most sense to make them and are then deployed to where they’re needed most.” But without any international standard or agreement, countries that do the right thing by allowing doses to be exported lose out, he said. India, the United States and the European Union — where the vast majority of vaccines are made today — have employed export controls that enable them to prioritize vaccinating their own citizens. But South Africa was contractually prohibited from doing the same. Even as the Delta variant wreaked havoc, Johnson & Johnson shots that were put into vials and packaged there (what manufacturers call fill and finish, the final step in the vaccine-making process) were shipped to Europe.

The world’s richest nations have tried to correct these imbalances by donating some of their vaccine surplus — to Covax in some cases and directly to lower-income countries in others — but donations are a flimsy fix for such rampant inequity. For one thing, the vast majority of doses pledged by Group of 7 countries in July have yet to be delivered. Also, the shots are only one item on a roster of needs that must be met for vaccination to succeed. Transportation, electricity for cold storage, trained health workers for vaccine administration and campaigns to combat hesitancy all need to be bolstered. So far, the United States has treated this list as zero-sum, planning to pay for its promised donation of 600 million doses by diverting funds that had been earmarked for vaccination programs in low-income countries.

The administration has managed to ship more than 110 million doses to countries around the world by early August. That’s an impressive feat. It took several years for the United States to donate lifesaving H.I.V. medications overseas, as administration officials are keen to point out. But it’s still just a tiny fraction of what lower-income countries need.

By some estimates, the world is poised to have 12 billion or so shots — enough to vaccinate more than 70 percent of its population — by the end of this year. But if current trends persist, very few of those shots will reach the poorest countries with the greatest need. To alter this grim calculus, public health officials say, more companies in more regions need to start making vaccines.

“Africa produces less than 1 percent of what it needs on the continent,” said Mo Ibrahim, a Sudanese philanthropist working to secure vaccine equity for Africa. “That is not sustainable. We need to boost manufacturing here. We need to build the infrastructure for storage and transport, and we need to join the global supply chain.”

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Credit…Brendan Mcdermid/Reuters

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Credit…Leo Correa/Associated Press

The potential advantages of what experts call distributed manufacturing are plain: It would be much easier to quash variants like Delta if each region of the globe had its own modern vaccine manufacturing hub capable of responding quickly to local needs. This would also leave the world much better prepared for the next pandemic and the one after that. The Coalition for Epidemic Preparedness Innovations said that regional facilities would make it possible to create shots within 100 days of dangerous diseases emerging and to stop outbreaks before they mushroom into pandemics. Public Citizen estimated that it would take $25 billion, and about six months, to establish a network of such hubs around the world and that if officials started today, the world could have billions more doses by this time next year.

The United States International Development Finance Corporation, a federal agency that funds and oversees private development projects in low-income countries, has offered at least $2 billion in incentives to companies in low-income countries to help spur vaccine development. But so far, the agency appears to have secured only fill-and-finish contracts, in which smaller companies finish and package the shots made by larger brand-name operations. The trouble with these contracts, critics say, is that the larger company retains control over the final product, including how much is made, where and when doses are shipped and at what price.

The barriers to increasing manufacturing capacity are legion. Factories have to be upgraded or built from scratch, and when it comes to novel mRNA vaccines, expertise is scant outside the world’s wealthiest nations. But the biggest hurdle, by far, appears to be the obstinacy of the world’s leading vaccine makers, which have largely refused to share their technology, even when it was developed with public money. For example, a technology transfer hub established in South Africa by the W.H.O. recently announced that it would aim to copy Moderna’s mRNA vaccine. But so far, the company has not agreed to share its technology or expertise with the hub, according to Reuters. The W.H.O. created a similar global technology transfer hub this year, but so far no companies or countries have agreed to join.

Industry leaders say that it will take years for outside companies or low-income nations to develop the infrastructure and expertise needed to make the shots themselves. Quality and safety would suffer, they argue. And so would innovation if they are forced to share their trade secrets with the world. But it’s hard not to see other motives. “What most of the established players really want is to keep control of their profits,” said Andrey Zarur, the C.E.O. of GreenLight Biosciences, a biotech company that’s developing mRNA technology. “They say, ‘We’ll hold on to the technology, but we promise we’ll be good citizens and make sure you get what you need.’ Africa has heard this a million times before, and they’re sick of it, because they know it never works out that way.”

It’s also true that vaccines are not easy to make. The mRNA shots, for example, require highly specialized equipment and hundreds of ingredients, most of which are not made in underresourced settings. For instance, a chemical capping agent that prevents the body from rejecting the vaccine’s mRNA is patent protected and is made by just one company. Even simpler vaccines tend to involve multiple companies and countries; almost no shot is made in just one place.

But these hurdles are not insurmountable. Russia, for example, managed to transfer its technology to scores of smaller companies, including in the global south, in a matter of months, as Nature recently reported. The country’s strategy was to not only license its intellectual property but also to send its experts to those companies to show them what to do.

Emerging technology promises to be simpler. Dr. Peter Hotez, the dean of the National School of Tropical Medicine at Baylor College of Medicine in Texas, and his colleagues have developed what’s called a recombinant protein vaccine. It can be grown efficiently in yeast cells, has no onerous storage requirements and should be easy to mass-produce anywhere. Univercells, a Belgian company, has built a vaccine manufacturing facility that can fit inside a shipping container and could theoretically be deployed almost anywhere in the world. (The Financial Times called it “Ikea-style manufacturing” for vaccines.)

And GreenLight Biosciences has developed a different, potentially simpler technology for making mRNA vaccines: Rather than produce the necessary components through a complicated string of in vitro processes, the company grows them in E. coli bacteria. The company is already using the technology to mass-produce RNA for a novel pesticide. (GreenLight is primarily an agricultural company.) If it succeeds in adapting its manufacturing processes for medical products, which have to be much cleaner and more sterile than agricultural ones, lower-income countries could use that method to produce billions of mRNA vaccines. “It enables you to transfer just one technology instead of dozens,” said Mr. Zarur. “And once you transfer it, the countries have that knowledge forever.”

The African Union has set a goal of scaling up manufacturing capacity to 60 percent of its total need by 2040. But low-income countries are not the only ones hoping to produce more vaccines. The European Union and Britain have been building more plants and securing contracts with more companies. And the United States has pledged to invest nearly $3 billion in domestic vaccine production. Whether these efforts clash with or complement one another will depend in part on what world leaders say at this week’s summit — and what they do after it concludes.

Above all, critics say, someone desperately needs to take charge. New facilities will take time to set up. There’s no telling what the demand for any given shot will be after they are built, and smaller regional operations may need subsidies to survive, especially at first. World leaders will have to decide who bears that cost and how. They will also have to figure out how to direct traffic. Where does manufacturing capacity exist? Which facilities can be upgraded quickly? Which ones can make mRNA shots, and which would be better dedicated to other options? “To me, the million-dollar question is, ‘Who does all of that?’” said Mr. Yadav. “We urgently need a system orchestrator to direct all these flows not just for this pandemic but for all future ones. And right now, we don’t have that at all.”

If countries commit to a global vision for vaccination and if they work together toward its realization, it’s possible the vast inequities of today will be avoided next time around. If individualism is allowed to prevail instead, the world’s resources will only grow more concentrated, and the world’s poorest nations will continue to be left out.

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Credit…Denis Balibouse/Reuters

In 2000, when malaria was still a leading cause of death in sub-Saharan Africa, the global health community launched what would become one of its simplest and most successful initiatives, providing insecticide-treated bed nets to as many households as possible. In the decades since, more than one billion nets have been distributed, and malaria mortality has plummeted. Similarly, H.I.V. ravaged low-income nations around the world, until a global campaign put forth a simple but forceful goal: to quickly get antiretroviral drugs to many more countries.

The struggle to end the Covid pandemic would benefit from a similar focus. “It’s a classic collective action problem,” said Zoë McLaren, a health economist at the University of Maryland, Baltimore County. “You have a problem with a really obvious solution that will only work if enough people get on board and work toward it. But nobody wants to be the first one to make the effort because if no one else follows, it will be in vain.” To resolve a collective action conundrum, she said, you need two things: a concrete goal and a convincing sales pitch.

Vaccinating the world against Covid will cost a lot of money, but almost any amount of money will be worth it. The pandemic has caused the global economy to contract by trillions of dollars and will cost the world trillions more if it’s allowed to fester. It will also require some short-term sacrifices: Wealthy nations will have to hold off on boosters and possibly on shots for young children until at least the higher-risk groups in lower-income countries have received their first doses.

It will also take patience. Building a truly global vaccination system will be an epic challenge and will almost certainly not result in a fresh abundance of vaccines in the immediate future. But at some point, if they’re serious about stopping this pandemic and preventing others, leaders will have to face those challenges. They might as well start now.

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Credit…Chamila Karunarathne/EPA, via Shutterstock

If Mr. Biden wants to lead the way, he will have to take an unequivocal stance on global vaccine equity. Surveys show that most Americans agree that other countries should get first doses before the United States claims boosters for the masses.

The president should also support the NOVID Act, a bill that would authorize spending some $34 billion on the global vaccination effort, and direct his administration to spend the $16 billion or so that Congress has already allocated for that purpose. Only a tiny fraction of that money has been put to use so far, an unconscionable missed opportunity.

He will also need to do more than support vaccine waivers at the World Trade Organization. He will have to press peer nations like Germany to do the same. And he will have to ask more of private industry. The United States has untapped leverage with Moderna. The government helped pay to develop the company’s intellectual property and holds a patent on and contractual rights to it. The United States also has leverage with Johnson & Johnson, which the government paid more than $1 billion for advance purchases and research support. One idea, reported on by Nature: Nudge Johnson & Johnson to make use of factories that are currently making the Sputnik V shot, which is similar to the Johnson & Johnson shot but has run into manufacturing troubles.

If Mr. Biden is really serious about vaccinating the world, he’ll have to set aside geopolitics and work with China and perhaps Russia to validate their vaccines for broader use. China’s vaccine producers Sinovac and Sinopharm have pledged to export two billion doses by the end of this year, and experts say the companies are capable of making even more. But their shots need to be more thoroughly vetted, and their manufacturing facilities need to be inspected and cleared. For either of those things to happen, the United States and the rest of the world will have to cajole, and collaborate with, China.

Even as the world waits for such leadership, progress is being made. The recombinant protein shot developed by Baylor College of Medicine has advanced to large-scale clinical trials. Mr. Zarur said that GreenLight Biosciences is planning to launch clinical trials for its mRNA vaccine in Africa next year. The company is planning to build a factory in South Africa that he said would be “controlled by local or regional needs and not the whims of the Western world.” What he and other prospective vaccine makers need most from U.S. officials is clarity, he said. Regulatory hurdles are myriad for a new vaccine, and the logistics of transport and distribution will have to be worked out with scores of nations.

“The previous administration did a hell of a job making it so that the United States would get a billion shots,” Mr. Zarur told me recently. “But the United States is supposed to stand for something bigger than just taking care of its own citizens.”