SA’s mRNA hub is a messenger from the future for all of Africa
Afrigen Biologics and Vaccines, a Cape Town-based pharmaceutical company, has made the continent’s first Covid-19 jab as part of the World Health Organization’s mRNA vaccine technology transfer hub. This bodes well for low- and middle-income countries that will benefit from its work.
In 2021, the World Health Organization (WHO) chose the South African pharmaceutical company Afrigen Biologics and Vaccines to host its mRNA vaccine technology transfer hub.
Afrigen will invent jabs made with mRNA technology and then train manufacturers in poorer countries to make the shots as well. The first vaccine, for Covid-19, has been made and will be tested in clinical trials from early next year to see how well it works.
In Africa, 99% of all shots given to people are imported. During the pandemic, this meant African countries were last in line to receive jabs because manufacturers first served wealthier regions where the vaccines were made – and which could pay more.
To help reverse this situation, the mRNA hub in South Africa will figure out how to develop new shots for diseases rampant in low- and middle-income countries and share their recipes and methods with selected manufacturers in poorer states. This is something international pharmaceutical companies mostly refuse to do.
Although the hub is located at Afrigen, the South African Medical Research Council also helps with research and the vaccine manufacturer, Biovac, will do larger-scale production for clinical trials.
mRNA, short for messenger RNA, is the genetic code that tells a cell in your body how to make proteins. An mRNA vaccine contains the code for a specific protein that looks like it comes from the germ that causes a disease you’re trying to fight.
So when you get the shot, your body makes these proteins, which prompts your immune system to produce antibodies that will fend off the actual germ if you get infected with it.
Although mRNA technology was discovered in the 1960s and has been tested in other vaccines such as for flu and later also Ebola, it was only during Covid-19 that it was used in jabs rolled out around the world.
Two such jabs, one made by the pharmaceutical manufacturers Pfizer and BioNTech (we use this one in South Africa) and another by Moderna, proved to work very well.
So far, Afrigen has developed a small batch of a new mRNA Covid-19 vaccine, largely based on information about Moderna’s jab.
Because the genetic code for antigens can easily be changed using mRNA technology, this method for making vaccines can be adapted more easily than the more traditional ones. This means Afrigen can use the same basic process for making its Covid-19 jab to develop vaccines for other diseases such as HIV, tuberculosis (TB), malaria and influenza.
In fact, Afrigen says it’s already working on finding a new, better TB jab than the one currently given to babies.
A glimpse inside
From the outside, it’s hard to tell that there are sophisticated labs in the building where the scientists are working. The two-storey red-brick building is tucked away between a plastic pipe manufacturer and a hydraulics company in Montague Gardens, an industrial area about 16km outside Cape Town. But it’s here that the world’s first mRNA vaccine technology transfer hub has found a home.
A scientist is working in the research and development (R&D) lab of the hub. To her right, there’s a polystyrene cooler box with more test tubes on ice. And about a metre from her work station there’s a special machine, called a spectrophotometer, into which she drips a drop of the contents from each test tube to measure the amount of DNA in each tube.
“The promise of mRNA technology is phenomenal,” says Petro Terblanche, Afrigen’s managing director. “Once you’ve established the [mRNA] platform and therefore have a plug-and-play system, the target is that you can start manufacturing a vaccine in 90 days.”
With an mRNA platform, a vaccine developer can potentially make shots for different diseases or for a new variant of a disease-causing germ without having to figure out the process from scratch each time. All that changes when you switch to working on a new shot is the genetic code with which the process starts and the quality checks during the process.
Think of it as using a ratchet wrench and socket set. The steps for making the product is the wrench; the code for making the protein that will elicit an immune response is a socket. Just like you would choose from a set of different-sized sockets to find the right fit for loosening a nut and then attaching it to the ratchet, so you could choose from mRNA sequences for different proteins and plug them into the production process one at a time.
The vaccine on which the scientist is performing tests uses the recipe for Moderna’s Covid-19 jab as a starting point. But because Moderna refused to share its exact methods and knowledge with Afrigen (or anyone else), the company had to figure out the process from documents that were available in the public domain. The final product, which Afrigen developed between September 2021 and February, is a new jab and not an exact copy of Moderna’s shot. Rather, it is based on the DNA code of Moderna’s vaccine.
Afrigen’s early studies in mice show not only that the jab gets the rodents’ immune systems to make antibodies, but also that the antibodies are good at inactivating the SARS-CoV-2 virus, which causes Covid-19.
Terblanche says these results suggest that the mRNA technology Afrigen developed works. “What Covid did is to unite the world in the quest for survival and we realised that access requires manufacturing capacity,” she adds.
Starting an mRNA vaccine
Across the corridor from Afrigen’s R&D lab is another, bigger one called the good manufacturing practice suite. Here scientists are covered in white disposable jumpsuits. The
outfits protect researchers from coming into contact with bacteria or introducing potential contaminants into the process. The staff also wear gloves and masks and there are stainless steel tanks called bioreactors, lots of tubes and pressure meters in the room.
The R&D lab is where scientists play and have fun; the manufacturing lab is where actual jabs get made.
The bioreactors are tanks in which bacteria are grown. Scientists put a ring of DNA, called a plasmid, into a small sample of bacteria to make a starter culture.
The plasmid carries the gene for the immune-prompting protein the vaccine will get your body to make. When the bacteria multiply, researchers get many copies of the plasmid, which they will eventually use to make lots of vaccine.
But this is just the first step for making an mRNA jab – there are six more before you have something that can go into people’s arms (see the sidebar for the full process).
Making an mRNA shot doesn’t need a big production plant. In fact, the development facility at Afrigen spans 380m², about the size of four two-bedroom townhouses next to one another. A setup of this size can produce, theoretically, about three million vials a year, says Caryn Fenner, an executive director at Afrigen. Three million vials will give 30 million doses because each vial contains enough for 10 shots.
The number of vials that can be pushed out in a certain time, however, depends not only on how long it takes to make the actual drug product (the stuff that goes into the vaccine that makes it work), but also on how long the quality tests take during the process to ensure the jab is safe to use. Fenner says making the drug product can be done in as little as seven days, whereas the various quality tests can add up to two months.
A hub with spokes
It’s not Afrigen that will mass-produce the shots it develops. For that, the mRNA hub model has something called “spokes”.
Spokes are vaccine manufacturers in lowand middle-income countries that the WHO has chosen to make the jab that Afrigen creates in large volumes.
Spoke companies won’t simply be getting a pack of instructions and then be left to their own devices. Instead, Afrigen’s scientists will train them, with people from the spokes coming to the hub to learn how to work with mRNA technology. Afrigen researchers will also do on-site visits at spokes’ premises to help them set up their facilities. One of the rules to become a spoke is that the country where a spoke is based must have a medicine regulator that has reached at least level three maturity according to WHO standards.
A level three rating means the regulator is stable and has “stringent, well-functioning regulatory systems” that are on a par with the standards of international authorities such as the US Food and Drug Administration. The South African Health Products Regulatory Authority was awarded this status in early October and a few other spoke countries, such as India, Ghana and Serbia, have received their status too.
Fenner says: “Some spoke companies have fairly advanced setups already, whereas others are building their facilities from scratch. But there’s no set way to design your space: the plant simply needs to meet clean-room requirements.”
The spoke that is part of the hub’s South African consortium is the vaccine manufacturer Biovac in Cape Town. Biovac already has some experience with mRNA technology, because it signed a deal with Pfizer and BioNTech last year to fill, cap and label vials of their mRNA jab.
So far, there are 15 biotech companies in Africa, Latin America, India and eastern Europe that have been chosen as spokes. By the end of September, six of them had already had their first set of training sessions at the hub, learning how to work with mRNA vaccine technology.
The Medicines Patent Pool (MPP), a UN-backed organisation that helps to negotiate licences for the generic production of medicines, will help the hub to sort out licensing agreements for the jabs that Afrigen develops. Although the intellectual property of the shots will be held by Afrigen, it will be made available to spokes for free and the MPP will help with “defining and negotiating terms and conditions of eventual agreements”.
So when will we see this Covid-19 jab in use? The WHO says approval in South Africa could be in 2024, and the spokes in countries that receive the technology should be able to secure approval shortly thereafter.
Charles Gore, executive director of the MPP, says: “This [the hub] is about empowerment. We cannot fail. This project has to work.”