Even if Moderna Declines – Other Pharma Partners Now Poised to Join South African mRNA Vaccine Hub Initiative Analysis 09/02/2022 • Kerry Cullinan Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to print (Opens in new window) Inside Afrigen’s R&D facility in Cape Town, South Africa – where scientists think they have copied Moderna’s COVID-19 mRNA vaccine recipe. CAPE TOWN – The COVID-19 mRNA candidate vaccine, developed in two months flat by South African scientists based on Moderna’s “recipe”, might be too late for this pandemic, officials leading the project told Health Policy Watch, on the eve of a high-level WHO visit to the Afrigen Biologics & Vaccines facility where the vaccine formula was recently replicated. Still, the new WHO co-sponsored mRNA vaccine technology transfer hub based in South Africa aims to fill a longer-term mission, asserts Martin Friede, the WHO coordinator of the initiative in Geneva, in an interview with Health Policy Watch. And that is to act as a “training hub” building out capacity for manufacturing cutting-edge mRNA vaccines in other low- and middle-income countries. And in the absence of a high-level commitment to support the mRNA hub from Moderna or Pfizer – other pharma partners with vaccine expertise have come forward, Friede said. “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,” said Friede, declining to name who those partners might be. He and other officials spoke to Health Policy Watch on the eve of a planned visit here Friday and Saturday by WHO Director General Tedros Adhanom Ghebreyesus to Afrigen and other South African institutions collaborating in the new hub initiative. The visit by Tedros, accompanied by Belgium’s Minister of Development Cooperation, will likely bring more news of the expanding partnership around the hub. Along with Afrigen, Tedros will also visit the Biomedical Research Institute, based at Stellenbosch University’s Tygerburg Medical Campus, and Biovac, among other collaborators in the new hub. While Afrigen is the R&D faciilty that is developing the vaccine, Biovac would provide for its manufacture, accoring to the WHO plan. Dr Tedros and Minister Kitir will be hosted by the Minister of Health, Dr Joe Phaahla, and Deputy Minister Mr Buti Manamela as they will visit facilities including Afrigen Biologics & Vaccines, the Biomedical Research Institute, and Biovac, among others. pic.twitter.com/RhlHG9ogDM — DEPARTMENT OF SCIENCE & INNOVATION (@dsigovza) February 9, 2022 Meanwhile, at Afrigen, while the development of the new mRNA vaccine formula is an R&D breakthrough, the way forward to actual manufacturer remains littered with questions. If the recipe can be demonstrated to be biologically equivalent to the Moderna vaccine, then the company might be able to bring it to market by next year, company CEO Professor Petro Terblanche, told Health Policy Watch. But without Moderna’s direct cooperation, the formula could take another three years to get through regulatory hoops, she admitted. “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 said. She predicts that the company will only know which way the vaccine is headed in August, when it has made and tested good manufacturing practice-compliant (GMP) batches. Vaccine’s development used ‘forward integration’ strategy While Afrigen is doing the R&D, Biovac would be the first spoke of manufacturing for Africa’s own mRNA vaccines In June 2021, a South African consortium including Afrigen, Biovac and the South African Medical Research Council (SAMRC) was chosen by the World Health Organization (WHO) to host a new international centre of excellence and training – now known as the mRNA vaccine technology “hub”. They were tasked with making an mRNA vaccine, then sharing its know-how with companies and countries globally that lack this technology. A parallel initiative, announced in September 2021, is also ongoing in Brazil’s Oswaldo Cruz Foundation and in Argentina’s Sinergium Biotech. When the South African hub was first launched, the WHO appealed to pharmaceutical companies to share their know-how. But Moderna and Pfizer-BioNTech did not respond. So Afrigen’s scientists had to take what was available in open published sources and try to figure it out for themselves (selecting Moderna over Pfizer simply because the company said that 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,” said Terblanche. Instead, Afrigen’s scientists used a process of “forward integration”, Terblanche explains. They based their vacccine on the actual 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 linearized and purified RNA and we encapsulated it”, she explains. But while the sequence and the raw materials are the same, the precise vaccine formula still 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. The World Health Organisation announced last year that South Africa will host Africa's first COVID mRNA vaccine technology transfer hub, an initiative that is fully supported by the Government of South Africa, and numerous other countries and health partners. pic.twitter.com/CiFsftkNbw — DEPARTMENT OF SCIENCE & INNOVATION (@dsigovza) February 9, 2022 Still hopes that other major pharma firm – may join initiative Terblanche remains hopeful another experienced pharma firm, will assist with scale-up as “there are always challenges when you scale it up so from the laboratory to big scale, making the vaccines”. Afrigen needs help with issues such as some of the standard operating procedures, including the formula ratios of the lipid nanoparticles that encapsulate the mRNA; 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. But so far, none of the big pharma firms with approved vaccines have come forward to offer such assistance. Friede, who has been reaching out to the pharma industry from his seat in Geneva, says that announcement of a pharma partner is pending. “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,” said Friede. While Friede said he was as yet unable to name the companies, Moderna and Pfizer are not among them, he confirmed. “What would have been great is if one of the companies that’s got approved vaccine 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 a 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.” May be too late for COVID – but not for other diseases Martin Friede, the WHO official who is coordinating the mRNA hub. Whatever the timeline may be, the senior WHO official who led the creation of the hub, sees it 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 Friede, himself an ex-pharma officer. As the leader of an earlier WHO global initiative to develop regional hubs for the manufacture of influenza vaccines, which operated between 2006-2016 – he’s also got extensive experience in what it really takes to build vaccine manufacturing capacity. In any case, if the more virulent forms of COVID really fade away over the 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 could still contribute in a practical way to squelching future rounds of SARS-CoV2, along with building regional capacity in mRNA vaccine manufacturing. Primary objective of hub is capacity building for future mRNA vaccines Inside Biovac – which is to be the first manufacturing spoke for the mRNA products produced by the South African Hub. A primary objective of the mRNA hub is not only to build capacity in South Africa, but to train young professionals from other low- and middle-income countries (LMIC) to acquire and use cutting-edge mRNA vaccine technology and production capacity. This can allow countries in the global South to respond more rapidly and agilely not only to COVID but also future disease threats, for which mRNA vaccines may be highly relevant – “and there will be future outbreaks”, Friede stresses. “We need to build a pipeline of other vaccines, for example HIV vaccines, to follow on after COVID to ensure that the facilities that we build are sustainable,” he explained in a recent video. Ensuring sustainability by diversifying mRNA applications for other diseases The investment in vaccine research, development and production is massive – the price tag for five years of the hub’s operation is $100-million. That’s another reason why diversification of mRNA applications to other diseases is critical – ensuring sustainability 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 Professor Richard Gordon, Director of International Partnerships at the South African Medical Research Council (SAMRC), another member of the hub consortium. “The SAMRC’s role is to put together a consortium of researchers to be developing 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 Africa Rift Nile fever,” adds Gordon. But Gordon warns that while many people have romantic ideas about mRNA vaccines, diseases such as TB and HIV still aren’t going to be easy vaccine targets- . In the coming months, the SAMRC will assemble a scientific advisory group to prioritise the diseases most likely to be quelched by mRNA vaccines, he adds. Staffing requirements another huge challenge 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 – approximately 1000 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. He cited the new 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 os 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 stresses. Hub set up in reaction to vaccine hoarding WHO Chief Scientist Soumya Swaminathan Said WHO Chief Scientist Dr Soumya Swaminathan, WHO decided to set up an mRNA hub in the face of vaccine hoarding by wealthy countries as well as export bans. India’s decision to ban exports of its locally-produced version of the Astra Zeneca vaccine, Covishield, during the spring 2021 Delta wave was devastating for the global COVAX vaccine facility – which abruptly lost its main supplier, the Serum Institute of India, that was contracted to supply hundreds of millions of vaccine doses destined to Africa and other low-income countries. “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’s not happened,” said Gore, echoing the disappointment of Terblanche and Friede. “But there may be licencing around second-generation technologies that we would like to incorporate,” adds Gore, who stresses that the mRNA hubs intend to strictly abide by existing patent rules. Eventually, the WHO intends to have at least one mRNA vaccine training and production hub in each of its six regions. Along with the identified sites in Argentina and Brazil for the Americas, other regions are expected to make announcements soon. -Elaine Ruth Fletcher contributed to this story Image Credits: Afrigen . Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to print (Opens in new window) Combat the infodemic in health information and support health policy reporting from the global South. Our growing network of journalists in Africa, Asia, Geneva and New York connect the dots between regional realities and the big global debates, with evidence-based, open access news and analysis. To make a personal or organisational contribution click here on PayPal.