Indexbit-How a scrappy African startup could forever change the world of vaccines

Imagine a world with vaccines not just for global threats like measles and IndexbitCOVID but for all the diseases that afflict people in the world's poorest countries – illnesses that are largely ignored but devastating, such as tuberculosis, dengue and lassa fever. And even for the ongoing epidemic of HIV.

Better yet, what if these new vaccines were actually invented and manufactured in the very countries where they are most needed. These are countries currently so shut out of global vaccine production they were forced to wait last in line for COVID vaccines. Yet if and when the next pandemic hits these nations wouldn't just have access to new vaccines, they could be at the forefront of creating them.

That's the vision that a tiny biotech startup in South Africa appears on track to make real. The company – Afrigen Biologics and Vaccines – is the linchpin of an unprecedented global project launched last year by the World Health Organization and various partners.

So what does this work actually look like? On a recent visit by NPR, Afrigen's Cape Town facility – a row of small warehouse-like structures – is a hive of activity.

Dreaming of vaccine independence

The courtyard echoes with bangs and grunts as construction workers race to assemble metal racks for new computer servers.

Contractor Jaco Neethling says this job feels personal. Like many South Africans he was outraged that people in his country had to wait months for COVID vaccines after the wealthy countries of the world got them.

"We always get the shortest end of the stick," says Neethling.

He says he's also keenly aware that the African continent as a whole makes just 1% of the vaccines it uses. "So it's nice to know that we can actually move forward. We can become independent," he says. "We've all bought into the dream."

How to choose the targets

Just inside the building, Afrigen's Managing Director Petro Terblanche is sorting through a heap of business cards on her desk.

"Look at this! Look at all these!" she says.

They are from researchers at universities and biotech firms from Korea, the United States — in fact, from all over the world – all of whom want to team up with Afrigen to quash a different disease.

"Yeah, And I've weeded them out," she adds. "I've already screened them!"

The idea is to harness the game-changing potential of mRNA vaccines. It's a new approach that basically identifies what part of a virus or bacterium the human body's immune system needs to latch on to in order to kill the pathogen. Scientists then create mRNA that is like a recipe book: when inserted into a person, it instructs their body to create many copies of that piece of the pathogen. The immune system then launches an immune response to those pieces by creating antibodies. If the real virus or bacteria ever infects the person, their immune system will then be ready to fight it.

So far, of course, this new technology has only been used in the highly effective shots against COVID. But in theory, mRNA vaccines could function as essentially a whole new plug-and-play system. Once a company knows how to make them for one disease, they can pretty quickly and cheaply modify them with mRNA for a totally different disease.

Except that so far only two companies — Moderna and Pfizer-BioNtech — have succeeded in making mRNA vaccines. And they're not sharing their know-how.

That's where this World Health Organization-convened effort comes in: WHO and its partners have enlisted Afrigen to figure out how to make mRNA vaccines — and then teach that know-how basically for free to manufacturers in low- and middle-income countries.

Each of the wannabe partners that has contacted Afrigen has hit on the key to preventing a different disease: In other words, the mRNA that could be useful against it. Afrigen would then use its expertise on how to deliver that mRNA into the body in order to create the vaccine.

Already Afrigen has agreed to work on mRNA vaccines against tuberculosis and HIV.

"Of course, we are giving priority to unmet needs," says Terblanche.

But it's daunting to choose from all the other promising partnership offers.

Terblanche gives a little gasp as she flips through the business cards. "All of these are, like, un ... be ... lievable!"

The mystery of the spots

A few doors down, in one of the lab rooms, three of Afrigen's scientists are peering at a tube of liquid, with a look of concern.

"Look on the sides of the tube," says Brandon Weber. "You'll see little spots there. Do you see?"

The team is confronting an even more pressing task at Afrigen: Completing what is supposed to be the company's inaugural mRNA vaccine — the one against COVID that will serve as proof of concept for the whole project.

Last May, Afrigen finalized a prototype that works in mice. Clinical trials in humans are set for this summer. But for that Afrigen will need to produce a huge quantity of the vaccine.

The lead scientist for the team in this room, Eden Padayachee, says that means developing a whole new system for production at mass scale.

So right now her team is testing each step. "It's troubleshooting," she says with a game smile. "If there's trouble — we gotta shoot the trouble."

And right off the bat they've run into this snag: The liquid into which they've dissolved the mRNA for the vaccine has these mysterious particles in it.

"They need to be removed," says Padayachee, "or it will clog the column" – a piece of equipment that's supposed to purify the solution.

Weber gets on the computer to see if it's possible to buy a microscopic filter that could strain out the particles. Within minutes he finds an option.

"Yeah, this may solve our problem," he says. Then his face darkens. "Uh, the lead time to get the product here is quite long," he says.

In the U.S. he could probably get it overnight. But here in South Africa? "Weeks," he says, shaking his head. "Weeks and months even."

A coming battle

Back in the executive suite, Terblanche says these kinds of issues have already delayed the project's mRNA vaccine against COVID by almost a year.

She sighs heavily. "Access to equipment. Access to raw material. It is endless!"

Another looming issue: patents. Afrigen's COVID vaccine incorporates some mRNA vaccine breakthroughs from Moderna's version – in part because some of that information was publicly known, and in part because Moderna has said it won't enforce its patents when it comes to COVID vaccines.

But will Moderna allow those same patented elements to be used for the mRNA vaccines against other diseases that Afrigen is developing? Terblanche gives a little shrug. "So the short answer is, I don't know which way Moderna's going to go," she says.

And that's just one of what Terblanche says is a "battlefield's" worth of patent holders Afrigen may have to contend with.

In anticipation, Afrigen is already trying to develop its own versions of some patented elements. It may also help that the WHO-led mRNA project is also supporting an effort by one other vaccine development oufit — a public agency in Brazil called the Bio-Manguinhos Fiocruz Foundation — to produce a wholly original new mRNA vaccine against COVID, whose elements they would then share.

Still, says Terblanche, there are almost certainly some patents out there that "complicate our lives." So she says "we may need to start a process of challenging some of the claims."

"Well," she adds quickly. "You talk first then you go to court." She starts to laugh. "We first have coffee and then we go to court!"

How to make a profit

Terblanche does at least have breathing room when it comes to Afrigen's business model.

Afrigen is a privately held, for-profit company, founded in 2014 by a non-profit research institute based in Seattle, Wa. and funded by a South African national industrial development corporation and a multinational investment group started by health-care professionals, with the express mission of expanding local manufacturing and increasing access to vaccines and therapeutics in Africa. So, says Terblanche, "not even the shareholders are wanting to make billions."

Still, to ensure the company is sustainable, she does need some profit. And Afrigen's deal with the international funders who backed the mRNA project limits how much it can make from any mRNA vaccines sold in low- and middle-income countries. So Terblanche is also seeking partners to help develop vaccines aimed at wealthy countries for diseases that affect them.

Speaking of which, an alarm on her computer is sounding. Terblanche points to the calendar on her screen.

"Meeting time!" she says.

Another video conference with a potential partner. She grabs a sheaf of papers – and another essential: "Warpaint!" It's what she calls her lipstick. Tomato red.

She starts to laugh again. "You can't look tired," she says, "if you want to change the world."