CAPE TOWN – Sustainability is the priority for vaccine manufacturers that are part of the mRNA technology transfer programme established by the World Health Organization (WHO) and the Medicines Patent Pool (MPP).

The programme was launched in 2020 to equip low and middle-income countries (LMIC) to make their own COVID-19 vaccines to address the inequity exposed by the pandemic – but few countries want or need these vaccines now. 

“The network was built on the premise of a COVID-19 vaccine market. What do the manufacturers do to stay alive?” asked Martin Friede, head of WHO’s vaccine development unit, at a three-day progress meeting in Cape Town.

The immediate priority is to ensure that the 15 partners in the network can “make commercially viable products that they can sell and that there are people out there who want these products,” he added.

Dengue, H5N1, malaria, cholera and Rift Valley fever (RVF) are some of the vaccines under research and development (R&D). Meanwhile, South Africa is putting much of its focus on trying to develop an mRNA vaccine for tuberculosis, the world’s biggest infectious disease.

Some manufacturers also looking at vaccines for zoonotic diseases like leishmaniosis, which affects people and animals, and animal vaccines to keep their new facilities “warm” and ready for the next pandemic.

MPP executive director Charles Gore said that manufacturers can also go beyond mRNA:  “We need monoclonal antibodies and immune modulators.”

But unless the manufacturers sell vaccines and other products to address the health challenges of their regions, they will either go bankrupt or move on to commercially viable products, and their new capacity will be lost by the next pandemic.

In 2023, the South African government, which hosts the mRNA hub, opted to procure pneumococcal vaccines from an Indian company rather than local company Biovac, which is part of the programme, because they were cheaper. In the meantime, the vaccine platform, Gavi, has set aside money to assist up-and-coming vaccine manufacturers particularly in Africa to compete in a tight market.

Amazing progress – and financial challenges

Despite the challenges, progress has been “really amazing,” said Gore of the programme that started in Cape Town, South Africa.

“We are now poised to establish a sustainable mRNA vaccine production capacity that will benefit millions across the Global South, truly redefining what health equity can look like on a global scale,” added Gore.

From zero mRNA manufacturing capabilities in LMICS at the launch, the initiative expects 11 state-of-the-art good manufacturing practices (GMP) certified mRNA manufacturing facilities to be launched in 10 countries by 2030 – two within the next year. 

Should this happen, the network will be able to make 60 million doses annually by 2030, with the potential to scale up to a maximum of two billion doses in the event of a pandemic. 

The initiative is supported by the governments of South Africa, France, Belgium, Canada, the European Union, Germany, Norway, and the ELMA Foundation.

“Despite remarkable progress, additional funding is required to fully achieve the programme’s ambition. An estimated $200 million is needed to advance all manufacturers to GMP standards and continue to strengthen the R&D pipeline in support of at least 12 mRNA products currently in development,” the MPP noted in a statement on Wednesday.

South Africa leads

South Africa was chosen to lead the initiative because of its strong research community and manufacturing sector, according to Gore.

Commercial company Afrigen was appointed as the “hub” of the programme. Within six months, its scientists had developed an mRNA vaccine based on the Moderna vaccine – although the drug company declined to offer any help.

Afrigen has since trained 15 partners to develop mRNA vaccines from Argentina, Bangladesh, Brazil, Egypt, India, Indonesia, Kenya, Nigeria, Pakistan, Senegal, Serbia, Tunisia, Ukraine and Vietnam. 

Afrigen expects to be GMP-certified within the next year but it too is challenged by the need for commercially viable products, particularly as money for the mRNA initiative only runs to 2026.

CEO Dr Petro Terblanche says her company and others in the network are exploring a variety of options to keep afloat including “blended finance” from governments, donors and development banks.

South African manufacturer Biovac is the manufacturing arm of the country’s consortium. It is in the process of developing a cholera vaccine which enters clinical trials next year.

Scaling up

Some of the partners, such as BioFarma in Indonesia and Egypt’s BioGeneric are not only honing their ability to make vaccines but scaling up their manufacturing capacity to produce millions of vaccines per year.

Biofarma’s Indra Rudiansyah said that the Indonesian company was expanding its site and had a candidate vaccine for rabies.

BioGeneric has four vaccines in the pipeline including rabies and polio, and now has fill-and-finish capacity to make 30 million vaccine doses a year. It has invested $50 million in expansion.

“But it’s very hard to know when we will reach profitability,” said Heba Wali, the company’s general manager.

Companies that are government-funded have more security. Bio-Manguinhos, which falls under Brazil’s science foundation, makes vaccines for the country’s public health programme.

“There is a very strong possibility that our government will use our mRNA COVID-19 vaccine,” said Patricia Neves of Bio-Manguinhos.

Kenya’s Biovax is 100% state-owned, and its government has procured a $120 million loan from the World Bank for its expansion. However, it’s biggest challenge is that it is unable to compete with the salaries paid by commercial companies. 

Meanwhile, Senegal’s Institut Pasteur Dakar, have gone from three employees to 16 and still are far from ready to manufacture vaccines.

Regional co-operation

But, said Friede, “most of the vaccine manufacturers on earth are not research entities. They are manufacturing entities. They go and buy their research from universities or biotech companies.

“How are we going to ensure that these manufacturers get access to a portfolio product that they can manufacture?”

To assist with this, R&D consortia have been set up to lead product-orientated research. Most consortia are aimed at developing vaccine candidates for diseases that are priorities in their regions. 

The consortia are bringing in experienced translational research groups like the International Vaccine Institute in Korea and Hilleman laboratories in Singapore and universities, said Friede.

At least 13 of the 15 partners and the WHO have also signed a memorandum of understanding with Professor Drew Weissman at the University of Pennsylvania, who is assisting in building their research development capacity and they will get access to the portfolio of products coming out of this. Weissman and Katalin Karikó won the Nobel Prize for Medicine in 2023 for their work on mRNA.

The Southeast Asia consortium is fairly advanced in its work on four mRNA vaccines for dengue, HPV, malaria and Enterovirus. Any vaccines developed through this initiative will be shared across participating LMICs.

Moderna has around 5,000 scientists, which is hard to compete with, added Friede. But the consortia are enabling the network to start building “the critical mass that is necessary to ensure that LMICs can get a portfolio of products that have been taken to a certain point in development and then transferred over”. 

“The point of the network is sharing and collaborating,” said Gore, adding that those in the network will get preferential treatment and access to products.

Image Credits: Kerry Cullinan, Rodger Bosch / Medicines Patent Pool.