The great vaccine ... bake off ... has begun

Fans of the television series The Great British Bake Off have long marveled at the skill contestants show during the dreaded "technical challenge" — for which they are given a basket with all the ingredients needed to make a highly unusual dish but a set of instructions that are often as vague as, "Bake until ready." Now a team of scientists at a pharmaceutical startup in South Africa is essentially confronting the same type of test — except the stakes are life and death.

The World Health Organization has hired the company, called Afrigen Biologics and Vaccines, as part of a $100 million plan to figure out how to make an mRNA vaccine against COVID that is as close as possible to the version produced by Moderna.

Until recently, Afrigen specialized in developing veterinary shots using fairly traditional methods. Now, says Afrigen's Managing Director, Petro Treblanche, the company's labs are a hive of research into the cutting-edge technology behind mRNA vaccines.

"You will see scientists in white coats and some with full personal protective equipment [suits] operating a bioreactor to make the actual DNA," says Treblanche. "You will see microbiology clean rooms where testing is taking place. You will see stability chambers where some of the products are put in to understand how stable they are in different environments of humidity and temperature."

Once Afrigen has sorted out all the complicated steps to make Moderna's shot on an industrial scale, WHO and other partners plan to pay Afrigen to become a teaching center.

"We call it a 'technology transfer hub,' " says Martin Friede, the WHO official in charge of this effort. "Manufacturers from around the world will be invited to come and learn the entire process. So this will accelerate the availability of the technology, not to one manufacturer but to many manufacturers."

Specifically manufacturers in low- and middle-income countries, Friede says the pandemic has shown they're sorely needed.

"There are regions on earth — the whole of Africa, for example, the whole of the Middle East — that really suffer because they've got no vaccine production capacity," says Friede.

At best some countries have "fill and finish" plants that can complete the final stages of packaging a vaccine. But Friede says the lack of soup-to-nuts manufacturers is a major reason that low- and middle-income countries have been all but boxed out of buying COVID vaccines. For instance, just 5% of people in Africa have gotten a full dose even as wealthy countries have vaccinated well above half of their populations.

Friede says it makes sense to set up more manufacturers of mRNA vaccines in particular because the technology appears so effective against COVID and because it shows promise against other diseases including malaria and tuberculosis.

As to why WHO has chosen to try to copy Moderna — rather than the other mRNA COVID vaccine, which is made by Pfizer BioNTech, Friede says the choice was practical.

"Moderna has reiterated on several occasions that they will not enforce their intellectual property during the pandemic," says Friede. In other words, a manufacturer probably won't face a lawsuit for producing a vaccine that's virtually identical to Moderna's.

Also, says Friede, compared to Pfizer's vaccine, there just happens to be a lot more information in the public domain about how Moderna's vaccine is made.

But Afrigen's Petro Treblanche says there are still a lot of unknowns. Take Moderna's patent.

"It's written very carefully and cleverly to not disclose absolutely everything," says Treblanche.

So while Afrigen has been able to determine most of the equipment and specialized ingredients that are needed, "what we don't know is the exact concentrations," says Treblanche. "And we don't know some of the mixing times — some of the conditions of mixing and formulating."

A particularly vexing question is how to replicate Moderna's "lipid nano-particle" — a special casing around the mRNA strand at the heart of the vaccine that keeps it stable as it travels through the body to, as Treblanche, "essential places like the spleen and lymph nodes."

"We understand other encapsulations," says Treblanche. But for all the expertise at Afrigen, "my team has never formulated a liquid nanoparticle."

Moderna is facing growing pressure to share this type of know-how. Last week several Congressional Democrats released a letter pointing out that Moderna got a massive infusion of U.S. taxpayer funds to help develop its vaccine. At least $1 billion for the research component alone. And they argued that President Joe Biden can and should use language in the government's contracts with Moderna to force the company to divulge its process.

When asked for comment, Moderna referred NPR to a statement on its website expressing that the company has a commitment to "protect as many people as possible around the globe." It notes that, among other steps to expand access to people in low income countries, Moderna has announced plans to build its own plant in Africa. The company has said it will begin searching for the location soon. Pfizer-BioNTech has made a similar announcement.

The WHO's Friede says this type of plant would have limited impact because it won't be teaching center. "But also — and this is very important," he says, "we need to make sure that it is owned by the Africans, and that the Africans are empowered." Otherwise there's no guarantee that in the event of a global supply crunch the doses wouldn't be shipped to the U.S. or Europe.

Stil, Friede says the WHO is talking to Moderna, and he remains hopeful the company will ultimately agree to provide some kind of tech transfer.

If so, Friede estimates it would cut the time it will take to get a manufacturer pumping out doses of the Moderna copycat vaccine from three or four years down to about two.

But even that could be too late, says Ramsus Bech Hansen, CEO of Airfinity, an independent London-based analytics company.

He says in recent months several of the existing manufacturers have ramped production to an "extraordinary" level. And he projects that by next year existing plants will already be providing more than enough COVID vaccines for the world.

This doesn't mean the effort centered on Afrigen is pointless. "But we should think about these regional initiatives more as preparation for the next pandemic."

WHO's Friede is less convinced that there will soon be sufficient COVID vaccine supply.

But even if that's the case, he says it will still be enormously valuable to have cracked the code of mRNA production on behalf of low and middle income producers.

All the more so, since an additional goal of the effort is to devise a COVID vaccine that can remain stable at much higher temperatures than the ones made by Moderna and Pfizer.

"That's a tall order," concedes Afrigen's Treblanche. But she says it's both do-able and vital--given how much of an obstacle the extreme cold chain required by the current mRNA poses in African countries with limited infrastructure.

"Moderna is the blueprint," she says. But in the long term, "this is about trying to make a vaccine that's even better." [Copyright 2021 NPR]