/ 28 November 2021

South Africa at the start of a Covid-19 vaccine the world has never seen

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The World Health Organisation has enlisted a team of South African researchers to produce a new mRNA Covid-19 vaccine, but with no recipe to follow, it’s not an easy task. (Photo by PATRICK HERTZOG/AFP via Getty Images)

In a small laboratory not far from the heart of Johannesburg, Patrick Arbuthnot is surrounded by technology — and test tubes.

Arbuthnot heads the Antiviral Gene Therapy Research Unit at the University of the Witwatersrand. Standing at his lab bench, Arbuthnot is just a few metres away from a high-powered microscope that reveals cells in tissues and molecules in cells. Behind him, a machine that could be mistaken for an office scanner is actually a gadget for parcelling out the unseen building blocks of our lives — DNA, RNA and other proteins.

Still, Arbuthnot’s attention is focused on something much lower-tech — a simple red and black notebook. In it, could be the start of a Covid-19 vaccine the world has never seen.

Africa produces less than 1% of the vaccines it uses

Almost 70% of people in the United Kingdom have been fully vaccinated against the SARS-CoV-2 virus. But less than 5% of people in low-income countries have received even one dose of a vaccine. In Africa, fewer than one in 10 people are fully immunised.

Vaccine inequality is nothing new for the continent. When swine flu broke out in 2009, rich vaccine-producing countries refused to export jabs until domestic needs were met. In 2010, children in countries such as Morocco and Algeria missed out on life-saving meningitis vaccines amid a global shortage.

At the time, a leading vaccine manufacturer was obliged to supply the United States and rich countries with doses first, recalls Mehdi Zaghloul, executive director of Morocco’s Sothema pharmaceutical company.

Less than 1% of vaccines used in Africa are produced locally.

Zaghloul continues: “As Africa, we need to ensure a minimum level of autonomy over our vaccine supply.”

Now Africa could be set to turn the page on history — and the first chapter is being written, in part, in Arbuthnot’s lab.

The WHO’s crack team of South African scientists

In June, the World Health Organisation (WHO) enlisted a team of South African researchers to crack the code for an mRNA Covid-19 vaccine and then teach others around the world to make it. South Africa will be the first of what the WHO envisions as several mRNA hubs, allowing more and more countries to produce the jabs locally.

Covid-19 vaccine manufacturers Pfizer and Moderna have refused to share their vaccine recipes with the WHO or partners. South African scientists are now piecing together what we know about the vaccines publicly — in part from patent applications — to develop an mRNA vaccine of their own that will be similar to Moderna’s.

They hope to produce a prototype for testing in the next year that is adapted to new variants and that, unlike current brands, does not need the ultra-cold storage that poses problems for developing countries without sophisticated refrigeration systems.

How do mRNA vaccines work?

Historically, vaccines have worked by using harmless versions of a germ — or proteins designed to look like a virus — to trick the body into churning out antibodies to fend off future illness.

Messenger ribonucleic acid (mRNA) vaccines are different, explains Kristie Bloom, Antiviral Gene Therapy Research Unit team leader for next-generation vaccines.

“Think of a cell inside your body as a little 3-D printer,” she says. “Messenger RNA is like a code that you send to that 3-D printer to get the cell to print — or produce — proteins.”

In the case of mRNA vaccines, this code teaches cells how to produce the proteins needed to mount a defence against SARS-CoV-2. This response snowballs, growing bigger and triggering different responses by your immune system.

Once the mRNA printing code has served its purpose, it simply disappears, Bloom says. Our cells — or printers — stop marking copies of the proteins. Still, the process leaves your immune system with a memory of how to fight the virus.

Cracking the code: Scientists are closer than you think

But mRNA’s disappearing act, known as instability, is also what makes vaccines like these tricky, says Arbuthnot.

Seated at a large round table, he is surrounded by stacks of papers, simple microscopes and, after almost a decade working on mRNA, piles of his black and red notebooks. His lab is the only one in Africa with a history of mRNA research, which is why the quest for an African Covid-19 vaccine begins here.

Naked mRNA degrades quickly. If mRNA in a vaccine disappears too soon, it won’t stick around long enough in the body to make the proteins needed to spark an immune response.

To stop this and help mRNA deliver its cellular printing code, vaccines like Moderna’s clothe mRNA in a protective layer of fats, or lipids.

“We know what lipids they put in, but the ratio is also very important,” Arbuthnot says. “We have a rough idea, but we don’t know what it is exactly and that’s not even available in their patents.”

Arbuthnot’s team is still figuring this out. Still, he believes they have already developed the mRNA sequence itself that will form the basis of their mRNA vaccine.

The end result won’t be a copy of the Moderna or Pfizer vaccine but a totally new mRNA vaccine, he says.

Do patents pose a threat?

The team at the University of Witwatersrand is busy teaching a group from South African company Afrigen Biologics and Vaccines to make mRNA technology. Other academic teams from around the country are also involved, using genome sequencing data plus the latest Covid-19 science to make sure any eventual vaccine is as variant-proof and powerful as possible before Afrigen starts production for clinical trials in the coming year.

It’s difficult to say when the jab would be publicly available. Doctors Without Borders (MSF) vaccine pharmacist Alain Alsalhani says Africa could have had an mRNA vaccine in as little as six months had Moderna or Pfizer shared their formulas.

Meanwhile, South Africa recently granted Moderna several far-reaching patents on mRNA technology that could potentially undermine efforts to get a new Covid-19 vaccine off the assembly line.

“One of these two patents is problematic because it’s extremely broad and basically would cover any mRNA-based technology, be it a vaccine or a therapeutic,” Alsalhani explains.

Provisions in international trade law exempt clinical trial research from patent protections, says Petro Terblanche, Afrigen’s managing director. But Moderna’s current patents could threaten future production: “The patents will prevent us from doing market authorisation and then distributing these vaccines,” she says.

In response, Moderna’s vice-president of medical affairs, Cesar Sanz Rodriguez, did not directly address questions about the effect of patents or the company’s participation in the WHO hub. He said Moderna plans to build a manufacturing plant in Africa to supply the continent.

Pfizer’s spokesperson for East and Southern Africa, Willis Angira, said the company is working to increase the amount of contract manufacturing sites — like the Biovac Institute in South Africa — to produce the firm’s Covid-19 jab for the continent.

“We remain committed to the responsible use of our intellectual property for the benefit of patients, and to collaborating with global health partners, as appropriate, to increase access to the Covid-19 vaccines,” Angira said.

Back in Johannesburg, Bloom is standing in the conference room of the Antiviral Gene Therapy Research Unit gazing at a scientific poster showing a map of Hepatitis B infections around the world. Africa’s high burden of illness means the continent is shaded a deep blue.

One day, she hopes to use mRNA technology to find a functional cure for the virus.

“There are people who are not very positive about the idea that South Africa and Africa could make their own vaccines. But we’re still very positive about making this work.”

This article is part of the Vaccine for the World series from the Evening Standard in London.