Aiming to break the rich world’s lockdown on mRNA vaccines: Goats and Soda: NPR

Gerhardt Boukes, chief scientist at Afrigen Biologics and Vaccines, formulates mRNA for use in a COVID-19 vaccine. The company, based in Cape Town, South Africa, is the linchpin of a global project to enable low- and middle-income countries to manufacture mRNA vaccines against all kinds of diseases.

Tommy Trenchard for NPR

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Tommy Trenchard for NPR

Gerhardt Boukes, chief scientist at Afrigen Biologics and Vaccines, formulates mRNA for use in a COVID-19 vaccine. The company, based in Cape Town, South Africa, is the linchpin of a global project to enable low- and middle-income countries to manufacture mRNA vaccines against all kinds of diseases.

Tommy Trenchard for NPR

For more than two years, Petro Terblanche has led a global effort to change the game: breaking the lock rich countries have on life-saving new vaccines so that low-income countries are no longer left in line.

Terblanche is the CEO of Afrigen Biologics and Vaccines, a South African pharmaceutical company that the World Bank and other partners have tapped to figure out how to make vaccines using new mRNA technology developed by Moderna and Pfizer to be used against COVID. None of these companies have shared their process. But if Afrigen can solve it, the next step in the plan will be for Afrigen to teach its know-how to scientists in low-income countries around the world.

An mRNA vaccine uses a new approach that essentially identifies the part of a virus or bacteria that the human body’s immune system must latch onto to kill the pathogen. Scientists then create an mRNA that’s like a recipe book: When it’s inserted into a person, it tells their body to make many copies of that piece of the pathogen. The immune system then launches an immune response against these pieces by creating antibodies. If the real virus or bacteria infects the person, then their immune system will be ready to fight it.

Compared to traditional vaccine methods, mRNA technology should be much easier to adapt to fight all kinds of other diseases beyond COVID. Afrigen’s work therefore has the potential to massively expand global access to vaccines.

Yet when NPR last reported on Afrigen’s progress last December, it was clear that the company faced serious obstacles. We called Terblanche to find out how far we’ve come since then.

Here is a progress report.

A major breakthrough

The broader goal of the “mRNA hub” effort — as the initiative is called — is to develop the capacity to produce mRNA vaccines more generally. But as a first test, Afrigen was tasked with making an mRNA COVID vaccine that it could prove was essentially a replica of Moderna’s version.

This required a series of reverse engineering steps, including figuring out how to make the mRNA used in the vaccine and then designing a way to encase that mRNA in a tiny fat particle so that it remains stable once inserted into the human body.

Afrigen now appears to have achieved this goal, says Terblanche. “We have demonstrated in a number of variables that we are comparable to Moderna,” she says.

These side-by-side comparison methods include studies that show Afrigen’s version of the vaccine behaves similarly to Moderna’s in mice. And, since last May, a series of “challenge” trials have been carried out in which hamsters were given the vaccine and then exposed to the coronavirus to show that Afrigen’s vaccine was just as effective as Moderna’s in preventing infection. ‘infection.

Just as significantly, Afrigen has sorted out the next step: proposing a system for manufacturing the vaccine on a scale large enough to produce the quantities needed for a human clinical trial.

Terblanche says getting to this point so soon after work began is “a phenomenal development.”

“If you had asked me 18 months ago,” she says, I would have said, “That’s not possible.” So I’m very optimistic.”

Train the rest of the world

As Afrigen masters each step, it also created a training program to pass this knowledge on to scientists in 15 countries currently participating in the mRNA hub effort, including Argentina, Bangladesh, Egypt, Nigeria, Serbia and Vietnam.

“We are not waiting until we have completed a turnkey process,” Terblanche notes, “because we are building capacity to deal with future pandemics. So speed is important.”

The company began by hosting a series of one-week practical courses for teams from each country at its Cape Town premises.

The invited scientists were chemists, biochemists and bioprocess engineers with extensive experience working on vaccines, Terblanche notes. “But almost none of them had ever worked on mRNA vaccines. This is a very different vaccine manufacturing platform.”

So, Terblanche says, “we train them in the science of mRNA vaccine production – to understand why mRNA is complex, why it’s unstable and how to make it stable, how to reduce impurities?

The Ukrainian team recently completed its visit. “We still need Kenya to come,” says Terblanche, “and then we will have achieved this first transfer of knowledge to the 15 partners. That leaves me with great satisfaction and enthusiasm.”

Afrigen has also completed preparation of the next training module – an information pack explaining how others can start manufacturing Afrigen’s mRNA vaccine. “The design of the facility, the equipment you will need, the raw materials, all the analysis,” Terblanche says. “This has also been sent to most partners.”

New variants cause delays

But the information pack only covers how to make small quantities of vaccine. Terblanche says it will take much longer to complete the next information package – on how to produce enough vaccines for human clinical trials.

Indeed, Afrigen ran into a problem: to definitively prove that its vaccine is legitimate, it still needs TO DO these clinical trials. “You know, hamsters and mice are not humans,” says Terblanche. “As scientists often say, mice lie.” And the company had to abandon plans to begin human trials last summer after it became clear that the original version of the COVID vaccine that Afrigen’s version is modeled after is not as effective as Moderna’s more recently updated version regarding the variants currently in circulation. of the coronavirus.

Continuing to perfect this product until it’s ready for commercial distribution “makes no ethical or financial sense,” Terblanche says.

Instead, Afrigen proposed a new alternative two-pronged strategy: complete validation of its current version of the vaccine in primates – and if successful, pass on information on how to produce this version to partner countries so that they can have at least this basic knowledge as a starting point for making different mRNA vaccines in the future.

At the same time, Afrigen is embarking on the development of a new mRNA vaccine against COVID, adapted to the most recent strains. Because this adaptation requires changing the content of the vaccine, it will add time, Terblanche says. Even in the best-case scenario, Afrigen probably wouldn’t be ready to start clinical trials until the third quarter of next year.

And it will take even longer to get up and running and produce this vaccine on a commercial scale.

“It’s still heavy,” sighs Terblanche. “Just a huge amount of work.”

Yet the fact that Afrigen is now able to develop a COVID vaccine against a new strain also suggests that some of the promise of the mRNA hub project is being realized.