Researchers at a South African biotechnology company say they have nearly completed the process of reproducing Moderna’s mRNA vaccine against COVID-19, without Moderna’s involvement.
The company, Afrigen Biologics and Vaccines in Cape Town, has made only microlitres of the vaccine, which is based on data that Moderna used to make its shot. But the achievement is a milestone for a major initiative launched by the World Health Organization (WHO) — a technology-transfer hub meant to build capacity for vaccine manufacturing in low- and middle-income countries.
During the COVID-19 pandemic, developers of mRNA vaccines — Moderna, based in Cambridge, Massachusetts, Pfizer, in New York City, and BioNTech, in Mainz, Germany — have sent more than 70% of their doses to wealthy nations, according to vaccine-distribution analyses. Meanwhile, millions of doses purchased by or promised to low- and middle-income countries have been delayed. “Moderna and Pfizer–BioNTech’s vaccines are mainly still going to just the richest countries,” says Martin Friede, the WHO official coordinating the hub. “Our objective is to empower other countries to make their own.”
Many steps remain before Afrigen’s mRNA vaccine candidate can be distributed to people in Africa and beyond, and it definitely won’t help to curb the pandemic this year. But the WHO hopes that the process of creating it will lay the foundation for a more globally distributed mRNA-vaccine industry.
Gerhardt Boukes, chief scientist at Afrigen — the firm at the core of the WHO’s hub —is proud to have helped with the first phase of the plan, which included creating messenger RNA that encodes a modified portion of the coronavirus SARS-CoV-2 and encapsulating it in a lipid nanoparticle that delivers the vaccine to cells. “We didn’t have help from the major COVID-vaccine producers,” he says, “so we did it ourselves to show the world that it can be done, and be done here, on the African continent.”
Going it alone
When the WHO launched its mRNA tech-transfer hub in South Africa last June, it asked Moderna, Pfizer and BioNTech to help teach researchers in low- and middle-income countries how to make their COVID-19 vaccines. But the companies did not respond, and the WHO decided to go ahead without their help. Friede says the WHO chose to replicate Moderna’s shot because more information on its development is available publicly, compared with Pfizer–BioNTech’s vaccine, and because Moderna has vowed not to enforce its patents during the pandemic. Moderna did not respond to requests from Nature to comment on the WHO’s decision to copy its vaccine.
With funds from countries including France, Germany and Belgium, South African researchers began chipping away at the project in late September. A team at the University of the Witwatersrand in Johannesburg took the lead on the first step: making a DNA molecule that would serve as a template to synthesize the mRNA. Although Moderna has controversially patented this sequence, researchers at Stanford University in California deposited it in the online database Virological.org in March last year.
Patrick Arbuthnot, director of gene-therapy research at the University of the Witwatersrand, says, “We were not intimidated, because mRNA synthesis is a fairly generic procedure.” Despite delays in the shipment of raw materials, the team completed this process in ten weeks and sent vials of mRNA to Afrigen in early December.
During this period, having heard about plans to mimic Moderna’s shot, scientists from around the world e-mailed Afrigen researchers to offer assistance. Some of them were at the US National Institutes of Health, and had conducted foundational work on mRNA vaccines. “It was extraordinary,” says Petro Terblanche, Afrigen's managing director. “I think a lot of scientists were disillusioned with what had happened with vaccine distribution, and they wanted to help get the world out of this dilemma.”
On 5 January, Afrigen’s researchers accomplished another tricky part of the process: they encapsulated the mRNA in a fatty nanoparticle made of a mixture of lipids. Boukes says they haven’t yet used Moderna’s specific lipid mixture, but rather one that was immediately available from the manufacturer of the machine that the laboratory uses to create lipid nanoparticles. The researchers plan to use Moderna’s lipid mixture as soon as one last analytical instrument arrives. After that, the team will analyse the formulation to ensure that it is truly a near copy of Moderna’s vaccine.
An empowerment process
The next set of challenges will be to make a lot more of the vaccine. Jason McLellan, a structural biologist at the University of Texas at Austin whose work was foundational to the development of several COVID-19 vaccines, says he is not surprised that South African researchers seem to have copied Moderna’s vaccine, but he adds that scaling up production of that original shot required a lot of extra innovation by manufacturers.
For the next phase of the project, several companies in the global south will learn from Afrigen and attempt to create batches of vaccine themselves, in preparation for testing the shots in rodents. The WHO expects a Moderna mimic to be ready for phase I trials in people by the end of November.
What will happen next year remains uncertain. Charles Gore, director of the Medicines Patent Pool in Geneva, Switzerland — an organization working with the hub that is devoted to expanding drug and vaccine access around the world — says that the initiative has no intention of infringing Moderna’s patents. Laboratory research is generally not subject to patent rules, Gore explains.
And he hopes that once the vaccine is ready for use, Moderna might then license its patents — or that by then, there might be alternatives that companies could produce without fear of a lawsuit. Scientists at several universities are currently developing next-generation mRNA vaccines that might be cheaper to make or not require the ultracold storage needed for Moderna and Pfizer–BioNTech’s vaccines.
Although the pace of this effort will not meet the urgent need for vaccines across Africa, many researchers from the continent are enthusiastic. A reliance on vaccines from wealthy countries and companies has proved dangerous during the pandemic — only about 10% of people in Africa have been fully vaccinated — and this initiative aims to help nations to protect themselves. “Global health’s dysfunction derives from power imbalances,” explains Olusoji Adeyi, president of the organization Resilient Health Systems in Washington DC. “Addressing that will come from countries in the global south developing their own capabilities and taking responsibility for their own health.”