However, if the vaccine developed by the South African biotech company, Afrigen, is the same as the Moderna vaccine, it might be able to skip some regulatory steps, says company CEO Prof Petro Terblanche.

“Our aim was to replicate the Moderna vaccine and that’s what we hope we have done. If there is equivalence, we might be able to fast-track clinical development. If there are variances, then we will have to go for longer-term clinical trials,” Terblanche told Health Policy Watch.

She estimates the company will only know this in August, when it has made and tested its good manufacturing practice (GMP) batches.

In June, Afrigen was chosen by the World Health Organization (WHO) as an international centre of excellence and training — now known as the mRNA vaccine technology “hub” — tasked with making an mRNA vaccine, then sharing its know-how with companies and countries that lack this technology.

When the hub was launched, the WHO appealed to pharmaceutical companies to share their know-how — but Moderna and Pfizer-BioNTech ignored this appeal. So Afrigen’s scientists had to take what was published and try to figure it out for themselves (selecting Moderna over Pfizer simply because the company said it wouldn’t enforce its patent during the pandemic).

“This is not reverse engineering, which implies that we’ve taken the actual vaccine, analysed that and worked backwards to meet the qualities and the composition of what we have analysed,” says Terblanche.

Instead, Afrigen’s scientists used a process of “forward integration”, says Terblanche, based on the sequence for Moderna’s Vaccine 1273, which was discovered by Stanford University and is in the public domain.

From that, “we made the plasmid using our own scientific knowledge base, our own instruments and our own process mapping; we made the pDNA, we linearised and purified RNA and we encapsulated it”, she explains.

But while the sequence and the raw materials are the same, the ratios might be different — simply because “we don’t know the ratios because we don’t have the Moderna tech transfer”.

“So we have not pressed the button to make a copy of the Moderna vaccine. We are innovating from a sequence,” Terblanche stresses.

Terblanche still hopes that Moderna or another mRNA vaccine manufacturer will assist with scale-up, as “there are always challenges when you scale it up from the laboratory to big scale, making the vaccines”.

Afrigen needs help with some of the standard operating procedures, the ratios of the lipids, mixing conditions and encapsulating conditions, she says.

“We’ll have to experiment until we get it right, or we can get assistance from Moderna or one of the other companies that have got it right, to fast-track us,” she says. 

Might be too late for Covid

The WHO sees the hub as a long-term investment to combat future pandemics and diseases endemic to Africa — and accepts that this vaccine candidate might be too late for the Covid-19 pandemic.

“We don’t really know how this pandemic is going to pan out,” acknowledges the WHO’s Dr Martin Friede, who coordinates the hub.

If it’s over in the next few months, becoming another seasonal disease with predominantly mild outcomes in a population that has acquired immunity, then “none of the vaccines that are still in development will be of much use”, Friede told Health Policy Watch.

But if it drags on and countries need to give citizens booster shots, then the South African vaccine will contribute to regional health. 

Either way, says Friede, the primary objective of the mRNA hub is to enable other low- and middle-income countries (LMIC) to have the technology and production capacity to respond to this and future outbreaks — “and there will be future outbreaks”, he stresses.

“And, at last, I’m pleased to say that a few biotech companies have said we are prepared to share with you some of our knowledge about how to scale up so that you don’t spend too much time,” says Friede.

While Friede says he’s unable to name the companies just yet, Moderna and Pfizer are not among them.

“What would have been great is if one of the companies that’s got approved vaccines came along and said ‘we’ll share with you our technology… we’ll share with you our data’. 

“If that was done, the South Africans would have been able to get a vaccine approved in the space of about 12 to 18 months. Without them, they’re still going to manage to get a vaccine made and approved, but it’s going to take at least three years.”

Ensuring sustainability

The investment in vaccine research, development and production is massive — the price tag for five years of the hub is $100-million, so it also needs to be sustainable beyond the current pandemic.

“Sustainability is really around developing a pipeline of vaccine candidates that are not necessarily for Covid, but for diseases of LMICs, particularly in Africa,” says Prof Richard Gordon, Director of International Partnerships at the South African Medical Research Council (SAMRC).

“The SAMRC’s role is to put together a consortium of researchers to develop vaccine candidates for life after Covid,” says Gordon.

“We are fundraising, making grants and ensuring a continuum of vaccine candidates for other diseases for when Covid is a thing of the past. We’re going to need to work on HIV vaccines, TB vaccines, HPV, Chikungunya and Rift Valley fever,” adds Gordon.

But Gordon warns that while many people have romantic ideas about mRNA vaccines, diseases such as TB and HIV aren’t going to be easy to develop vaccines for. In the coming months, the SAMRC will assemble a scientific advisory group to prioritise the diseases most likely to be stopped by mRNA vaccines, he says.

But Gordon admits that the part of the hub that keeps him awake at night is how to ensure that there are enough skilled people to scale up vaccine production — about 1,000 people are going to be needed to staff the various vaccine initiatives in the country in the next few years.

“There are a number of initiatives on the way around capacity development, and the MRC is really trying to be involved in many of them,” he said, mentioning the WHO Academy, the Pan-African Vaccine Manufacturing group, and a soon-to-be-launched SAMRC scholarship programme being financed by billionaire Patrick Soon-Shiong.

Needs range from PhD graduates to new graduates in life sciences able to move into private tech companies. The new WHO Academy in Berlin is expected to help with training.

Terblanche says Afrigen will be working with the SAMRC to look at other vaccine candidates — adding malaria, Lassa fever, ebola and Schistosomiasis (bilharzia) to the list of possibilities.

“This facility was not designed for Covid-19 only. What we have built is a facility that has the ability to produce vaccines end-to-end from sequence right through to the final fill-finished product, and to be multi-purpose and multi-product,” she says.

Hub set up in reaction to vaccine hoarding

The WHO decided to set up an mRNA hub in the face of vaccine hoarding and export bans by wealthy countries, says WHO chief scientist Dr Soumya Swaminathan.

“It became very obvious that the countries that were suffering the most were those that were dependent entirely on imports,” says Swaminathan, adding that the WHO decided to establish a “multilateral mechanism for technology transfer”.

“The concept here is that it is a global hub that shares technology with anybody who wants to receive it, focusing on LMIC countries and those which do not have adequate capacity,” says Swaminathan, adding that mRNA was chosen because it has “immense potential” for other diseases, not just Covid-19.

The Medicines Patent Pool (MPP) is supporting the hub with licensing and fundraising, says executive director Charles Gore. France has already made a substantial donation to the hub.

The @MedsPatentPool
(MPP) & #Afrigen have signed an agreement to allow the 🇿🇦 company to establish itself as the global #mRNA vaccine technology transfer hub. #TeamEurope pic.twitter.com/0w2pwss3lI

— France in S. Africa (@FrenchEmbassyZA) February 3, 2022

“We had hoped that some of the originators of the current vaccines would come to us and agree to licence their technology to us… that has not happened,” says Gore.

“But there may be licensing around second-generation technologies that we would like to incorporate,” adds Gore, who stresses that the mRNA hubs will abide by patents.

Meanwhile, the WHO intends to have at least one mRNA vaccine production facility in each of its six regions — Argentina and Brazil have already been identified as the sites for the Americas. The other regions will make announcements soon. DM/MC