Rekubit-Whatever happened to the project to crack the wealthy world's lock on mRNA vaccines?

For more than two years Petro Terblanche has been spearheading a global effort with a game-changing goal: Break the lock that wealthy countries have Rekubiton life-saving new vaccines so that lower-income nations are no longer left waiting last in line.

Terblanche is the CEO of Afrigen Biologics and Vaccines, a South African pharmaceutical firm that the World Bank and other partners have tapped to figure out how to make vaccines using the new mRNA technology that Moderna and Pfizer developed for use against COVID. Neither of those companies has shared their process. But if Afrigen can crack it, the next step in the plan is for Afrigen to teach its know-how to scientists from lower-income countries around the world.

An mRNA vaccine uses 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.

Compared to traditional vaccine methods, mRNA technology is expected to be far easier to adapt to fight all manner of other diseases beyond COVID. So Afrigen's work has the potential to massively expand global access to vaccines.

Still, when NPR last reported on Afrigen's progress last December, it was clear that the company was facing some serious obstacles. We called Terblanche to find out how much headway they've made since.

Here's a progress report.

A major breakthrough

The larger goal of the "mRNA hub" effort – as the initiative is called – is to develop the capability to produce mRNA vaccines more generally. But as a first test, Afrigen was tasked with making an mRNA vaccine against COVID that it could prove was essentially a replica of Moderna's version.

This required reverse engineering a raft of steps – including figuring out how to make the mRNA that is used in the vaccine and then devising a way to encase that mRNA in a tiny fat particle so that it remains stable once it's inserted in the human body.

Afrigen now appears to have accomplished this, says Terblanche. "We've demonstrated in a number of variables that we are comparable with Moderna," she says.

These side-by-side comparison methods include studies that show that Afrigen's version of the vaccine behaves similarly to Moderna's in mice. And, as of last May, a series of "challenge" trials were completed in which hamsters were given the vaccine and then exposed to the coronavirus to show that the Afrigen vaccine was just as effective as Moderna's in preventing infection.

Just as significantly, Afrigen has sorted the next step: coming up with a system for manufacturing the vaccine at a large enough scale to produce the quantities that would be needed for a clinical trial in humans.

Terblanche says that to have reached this point so soon after the work began is "a phenomenal development."

"If you'd asked me 18 months ago," she says, I would have said to you, 'It's not possible.' So I'm very upbeat."

Training the rest of the world

As Afrigen has mastered each step, it's also created a training program to pass on that knowledge to the scientists from 15 countries currently participating in the mRNA hub effort – including Argentina, Bangladesh, Egypt, Nigeria, Serbia and Vietnam.

"We're not waiting until we have finished a turnkey process," notes Terblanche, "because we are building capacity for future pandemics. So speed is important."

The company began by arranging a series of weeklong hands-on courses for each country's team at their Cape Town facility.

The visiting scientists were chemists, biochemists and bioprocessing engineers with deep experience working on vaccines, notes Terblanche. "But almost none of them had ever worked on mRNA vaccines. It is a very different vaccine manufacturing platform."

So, Terblanche says, "we train them on the science of mRNA vaccine production – to understand why mRNA is complex, why it's unstable and how do you make it stable, how do you reduce the impurities?"

The team from Ukraine recently wrapped up its visit. "We still need Kenya to come," says Terblanche, "and then we will have completed this first knowledge transfer to all 15 of the partners. That leaves me with absolute great satisfaction and excitement."

Afrigen has also finished putting together the next training module – an information package explaining how others can get started on making Afrigen's mRNA vaccine. "The design of the facility, what equipment you will need, what raw materials, all the analytics," says Terblanche. "That has been sent to most of the partners too."

New variants cause delays

But the info package only covers how to make small quantities of the vaccine. Terblanche says it's going to take a lot longer to complete the next info package – on how to produce enough vaccines for clinical trials in humans.

That's because Afrigen has hit a snag: In order to definitively prove that its vaccine is legitimate it still needs to actually do those clinical trials. "You know, hamsters and mice are not humans," says Terblanche. "As scientists often say, mice lie." And the company had to scrap plans to start the human trials this past summer after it became clear that the original version of the COVID vaccine that Afrigen's version is modeled on is not as effective as Moderna's more recently updated version when it comes to currently circulating variants of the coronavirus.

Continuing to perfect that product until it's ready for commercial distribution "does not make ethical and financial sense" says Terblanche.

Instead, Afrigen has come up with a new two-pronged alternative strategy: Finish validating its current version of the vaccine in primates – and if that is successful, pass on the information on how to produce that version to the partner countries so that they at least have that baseline knowledge as a starting point for making different mRNA vaccines in the future.

At the same time, Afrigen is getting started on developing a new mRNA vaccine against COVID that is tailored to the more recent strains. Because this adaptation requires changing the content of the vaccine, it's going to add more time, says Terblanche. Even in the best case scenario, Afrigen likely wouldn't be ready to start clinical trials until the third quarter of next year.

And it will take even longer to get set up to produce that vaccine at commercial scale.

"It's still heavy lifting," says Terblanche, with a sigh. "Just a massive amount of work."

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