As pandemic raged, global south lacked vaccines. Never again, researchers vow.

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Once it became clear that wealthy nations would help themselves to coronavirus vaccines long before poorer nations had access, researchers across Africa, Asia and South America banded together with the World Health Organization. Never again, they vowed, would they allow themselves to be at the mercy of the Western world while a deadly pathogen tore through their regions.

They launched a sprawling initiative that included companies and institutes in 15 middle-income countries in the global south, the half of the world longing for coronavirus vaccines in 2021 even as wealthy countries stockpiled doses. The groups aimed to develop their ability to produce messenger RNA vaccines. The first vaccines would protect against the coronavirus. And after that, they hoped to generate mRNA vaccines against other diseases, including yellow fever, tuberculosis and whatever scary virus emerges next.

Now, two years after the initiative’s start, the market for coronavirus vaccines has dwindled, and governments have turned their attention to other emergencies, such as the war in Ukraine. But the groups involved with the project continue to push forward. Called the mRNA vaccine technology transfer hub, a mouthful meant to reflect their intention to share mRNA technology, the initiative is distinct from the typical, competitive mode of drug development in which companies keep discoveries secret.

On a crisp, hillside lawn down the road from WHO’s Geneva headquarters, that agency’s project coordinator reiterated the organization’s commitment at a side event May 23 at the World Health Assembly. He and others discussed ideas for how the hub would stay afloat after some $117 million in funds runs out.

The damage caused by global vaccine inequity in 2021 was still fresh on people’s minds in Geneva. One study estimates it caused more than 1 million deaths in the global south. It also resulted in lasting damage to already weak health systems and, some scientists asserted, gave rise to the delta and omicron coronavirus variants, as India and southern Africa faced unmitigated surges of covid-19.

“Covid has put a magnifying glass upon the fissures and cracks in our world,” said Ayoade Alakija, co-chair of the African Vaccine Delivery Alliance, a group established by the African Union that aims to ensure that the continent can access vaccines against the coronavirus and other health threats. “This world is deeply, deeply unjust and inequitable.”

To avoid a repeat, big pharmaceutical companies, based predominantly in the United States and Western Europe, are building outposts in African countries and have signed a pledge to set aside doses for poorer countries during future pandemics.

In contrast, the smaller companies and institutes involved in the hub initiative are locally owned and operated, an assurance that the vaccines they hope to produce would serve people in those regions first.

The pandemic left an enduring lesson: National interests trump altruistic intentions, said Sotiris Missailidis, director of innovation at the government research institute Bio-Manguinhos/Fiocruz in Rio de Janeiro, the Brazilian hub in the initiative.

“The pandemic showed us that you can’t depend on others when the whole world is competing for a resource,” Missailidis said. “We need to make our own.”

Since the project’s start, hubs in Argentina, Bangladesh, Brazil, India, Indonesia, South Africa and Vietnam have built laboratories to develop mRNA vaccines. By early next year, Brazil expects to start clinical trials on its mRNA vaccine against the coronavirus.

Hubs that launched in countries with smaller biotechnology sectors, such as Senegal and Tunisia, have instead installed new equipment to conduct research on mRNA vaccines that might target diseases such as rift valley fever and leishmaniasis.

The United States has not funded the initiative thus far. The bulk of the program’s funds are from Canada, France and the European Commission.

Barney Graham, a virologist who led development of mRNA vaccines at the National Institutes of Health, is an adviser to the hub initiative because he believes it could be crucial to curbing the next pandemic. If the hubs can churn out mRNA vaccines rapidly when novel pathogens emerge, they might prevent localized outbreaks from spreading around the world.

“It is in everyone’s best interest if more places can find solutions to their own regional problems,” Graham said.

For that to happen, the hubs must remain open and operational between now and when the next outbreak explodes.

“Our biggest worry is that in 10 years’ time, we suddenly have another pandemic, we call them up and they say, ‘Oh, that facility? Well, we park cars in there now,'” said Martin Friede, coordinator of vaccine research at WHO. But the road ahead may be long. In addition to developing vaccines and plants to produce them in large quantities, several countries must strengthen their regulatory agencies to ensure the vaccines are safe.

The project’s complexity mirrors the problems it’s trying to solve. It’s not simply a matter of building vaccine manufacturing plants, said Jean Kaseya, director general of the Africa Centers for Disease Control and Prevention. “We are talking about job creation, we are talking about economic growth.”

For others, the goal of the initiative is to alter a fundamental imbalance that has repeatedly left the global south reliant on the north. For decades, lifesaving treatments have trickled down to developing countries. As the HIV epidemic surged in Africa in the early 2000s, hundreds of thousands of people died without access to antiretroviral drugs that arrived on the continent only several years after they became widely available in Australia, the United States and Western Europe.

One barrier that has prevented many lower-income countries from producing their own supplies is the expense of vaccine development and production.

Traditional vaccine technologies rely on inactivating live viruses, or growing proteins within large vats of living cells or within fresh chicken eggs. These steps require lots of space, equipment and biological processes that are finicky and can fail.

Graham considers mRNA technology a potential game changer because it relies on more predictable chemical processes with a smaller manufacturing footprint. It means that small laboratories can generate vaccine candidates to test at a faster clip, saving time and money.

But mRNA vaccines so far have proved effective against only the coronavirus. In April, scientists from some 20 countries convened at the initiative’s flagship hub, a small biotechnology company called Afrigen Biologics and Vaccines, in Cape Town, South Africa. For a few long days, they hashed out what sort of mRNA vaccines to try to create now that the demand for shots against the coronavirus has waned.

Afrigen had succeeded in reproducing Moderna’s mRNA coronavirus vaccine in January 2022 based on publicly available information, after the company declined to license its technology to the initiative. Since then, Afrigen has been tweaking the recipe and studying the vaccine’s protectiveness in rodents. But Petro Terblanche, Afrigen’s CEO, said the company no longer plans to test it in clinical trials because those are logistically complicated now that most South Africans have been infected or vaccinated. Plus, demand for coronavirus vaccines is now low in South Africa.

Still, she said, the process of developing a Moderna-like vaccine has allowed the company to build up its facility to meet high international standards for safety in mRNA vaccine production. They have begun research on an mRNA vaccine against tuberculosis, which would target a few proteins on the tuberculosis bacterium, identified at the University of Cape Town.

Tuberculosis is a leading killer in the country, causing some 58,000 deaths in 2019. Although the impact of a vaccine would be massive, Terblanche expects development could take a decade because the tuberculosis bacterium is biologically more complicated to target with vaccines than many viruses, including the coronavirus SARS-CoV-2. So, Afrigen is also looking into the potential for an mRNA vaccine against the virus that causes rift valley fever, in collaboration with the hub in Senegal.

In Brazil, at the hub at the Fiocruz institute, researchers dared not reproduce Moderna’s vaccine because the country – with a large, middle-income population and therefore a sizable market – faces higher patent barriers. Whereas Moderna promised not to enforce its patents on the hub in South Africa, the company provided no such assurance in Latin America.

Another barrier, Missailidis said, was that when Brazilians were desperate for coronavirus vaccines in 2021, Fiocruz signed a deal with the British pharmaceutical company AstraZeneca promising they wouldn’t make vaccines originally produced in other countries in exchange for a license to produce AstraZeneca’s shots. As a result, they may not be able to transfer in the mRNA vaccine that their South African collaborators have made.

Still, Brazilian immunologist Patricia Neves was excited a few months ago about her team’s latest results at Fiocruz. An mRNA vaccine they based on a different fragment of the coronavirus than those targeted by Moderna and other groups had evoked strong immune responses in mice. And they were testing a related vaccine that includes genetic instructions that direct the mRNA to replicate itself within cells. In theory, that would lower the amount of vaccine needed per dose, lessening costs.

The Brazilian hub hopes early next year to compare one of its mRNA vaccine candidates to booster doses from Moderna or Pfizer in clinical trails. If it proves as effective, Missailidis said the Brazilian government would probably purchase the Fiocruz vaccines because they would be less expensive.

“As a public institution, we can only add a 20 percent margin above the cost of production when we sell to the government,” Missailidis said. He estimated a price of about $1.50 a dose, compared with more than $20 for products from the big pharmaceutical companies.

The group has also begun to explore leishmaniasis.

Meanwhile, the hub in Bangladesh, at the biotechnology company Incepta Pharmaceuticals, hopes to develop a vaccine to protect children against the deadliest form of diarrhea caused by rotaviruses. Although that appears biologically feasible, Friede said, that vaccine might struggle to find a market because generic rotavirus vaccines, made on more traditional platforms, cost less than $1 a dose.

Market realities are top of mind for Friede because he participated in a project 17 years ago to build production facilities for pandemic influenza vaccines across the global south. By 2016, only a couple of the facilities retained the capacity to churn out the vaccines should another flu pandemic emerge.

Friede said this time around, the outcome may be different given the efficiency of mRNA technology. The flu vaccines required plants to continuously stock thousands of fresh, fertilized chicken eggs ordered from farmers in advance. When the vaccines weren’t in demand, eggs were wasted.

Another reason for hope is that the mRNA initiative has sustained interest from influential groups, including the biggest buyer of vaccines for lower-income countries, the Gavi vaccine alliance. Gavi has pledged support by offering to pay extra for vaccines produced in Africa – although it hasn’t contributed money to the effort, as Operation Warp Speed did in the United States, or specified the size of the extra payment.

Creating a more equitable world for vaccines is no longer a question of technological innovation, said Graham. “We have the science to do the right things if we had the political will.”