With made-in-Africa mRNA vaccines, a small Cape Town company wants to stand up to Big Pharma

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When Africans began dying from the fast-spreading new coronavirus in early 2020, the talented young biochemist Hapiloe Maranyane was unemployed and disheartened. Nobody seemed to recognize that African scientists such as herself could fight the pandemic if given the opportunity.

Despite her doctorate in medical biochemistry and extensive post-doctoral work, the Lesotho-born scientist had been jobless for six months in South Africa and was thinking about emigrating. As the pandemic wore on, her parents fell sick with serious illnesses from COVID-19. Relatives and close friends died. It was a time of trauma and frustration and an “overarching paralysis,” she recalls.

But this year, everything changed. African vaccine research finally gained funding, and Dr. Maranyane was hired by a pioneering new manufacturer in Cape Town to help develop the continent’s first mRNA vaccines. It’s a potentially historic step toward challenging the world’s pharmaceutical monopolies and conquering some of Africa’s most intractable diseases, from HIV to tuberculosis and malaria.

Dr. Maranyane works for Afrigen Biologics & Vaccines, a small but fast-growing South African company that hosts the World Health Organization’s vaccine technology transfer hub, an experiment in open-sourcing and tech-sharing. Its five-year budget of US$117-million includes $15-million from the Canadian government.

“It feels like a dream come true, to be able to find solutions to real problems, for Africa, by Africans,” Dr. Maranyane told The Globe and Mail.

“A lot of capable scientists tend to leave, because there isn’t the market for them,” she said. “I hope to be part of writing a different tale. This will inspire other work on the continent.”

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The needs are desperate. Africa consumes 25 per cent of the world’s vaccines, but 99 per cent of these are imported, and the costs are often prohibitive. During the COVID-19 pandemic, the continent was fully dependent on imported vaccines, which arrived so late that millions of Africans fell sick or died. Producers gave priority to wealthier countries, including Canada, which used their financial muscle to secure far more doses than they needed. Poor countries were forced to wait for much-delayed donations.

Now, despite non-co-operation or outright opposition from the leading Western vaccine manufacturers, Afrigen is progressing more swiftly than anyone had expected.

After achieving success in tests with mice this year, the company plans to begin manufacturing its COVID-19 shots by February or March. It aims to launch human trials in South Africa by May, while also training its partners in 15 countries (mostly in the developing world) to make the same vaccine.

“In less than 20 months, we’re going from zero to manufacturing,” said Petro Terblanche, managing director of Afrigen, in an interview with The Globe. “We had no facility, no license. I can’t believe it. How the hell are we doing it?”

15 vaccine manufacturers that will receive the mRNA technology from Afrigen, a biotech company based in Cape Town, South Africa

1

15

14

2

13

3

4

12

5

6

7

8

9

10

11

1

Ukraine

Darnitsa

8

South Africa

Biovac

9

Kenya

TBD*

2

Serbia

Institut Torlak

10

Egypt

BioGeneric

Pharma S.A.E.

3

Tunisia

Institut Pasteur

de Tunis

11

Indonesia

Biofarma

4

Brazil

Bio-Manguinhos

12

Vietnam

Polyvac

5

Senegal

Institut Pasteur

de Dakar

13

Bangladesh

Incepta Vaccine Ltd.

6

Argentina

Sinergium Biotech

14

India

BiologicalE

7

15

Nigeria

Biovaccines

Nigeria

Pakistan

National Institute

of Health

THE GLOBE AND MAIL, SOURCE:

MEDICINES PATENT POOL

15 vaccine manufacturers that will receive the mRNA technology from Afrigen, a biotech company based in Cape Town, South Africa

1

15

14

2

13

3

4

12

5

6

7

8

9

10

11

1

Ukraine

Darnitsa

8

South Africa

Biovac

9

Kenya

TBD*

2

Serbia

Institut Torlak

10

Egypt

BioGeneric

Pharma S.A.E.

3

Tunisia

Institut Pasteur

de Tunis

11

Indonesia

Biofarma

4

Brazil

Bio-Manguinhos

12

Vietnam

Polyvac

5

Senegal

Institut Pasteur

de Dakar

13

Bangladesh

Incepta Vaccine Ltd.

6

Argentina

Sinergium Biotech

14

India

BiologicalE

7

Nigeria

Biovaccines

Nigeria

15

Pakistan

National Institute

of Health

THE GLOBE AND MAIL, SOURCE: MEDICINES PATENT POOL

15 vaccine manufacturers that will receive the mRNA technology from Afrigen, a biotech company based in Cape Town, South Africa

Ukraine

Darnitsa

Pakistan

National Institute of Health

India

BiologicalE

Serbia

Institut Torlak

Bangladesh

Incepta Vaccine Ltd.

Tunisia

Institut Pasteur de Tunis

Vietnam

Polyvac

Senegal

Institut Pasteur de Dakar

Nigeria

Biovaccines

Nigeria

Argentina

Sinergium Biotech

South Africa

Biovac

Egypt

BioGeneric Pharma S.A.E.

Brazil

Bio-Manguinhos

Kenya

TBD*

Indonesia

Biofarma

THE GLOBE AND MAIL, SOURCE: MEDICINES PATENT POOL

Some Western pharmaceutical executives had cast doubt on Africa’s ability to manufacture complex vaccines, but Afrigen is proving them wrong. After launching its mRNA research barely a year ago, Afrigen can already produce fresh batches of the vaccine’s active ingredient in just seven days. Vaccines for other neglected diseases are already in the early planning stages.

“The progress has been phenomenal,” Prof. Terblanche said. “We know time is of the essence. We know that failure is not an option. We couldn’t ponder alternatives.”

Charles Gore, director of the Medicines Patent Pool, an international agency helping WHO establish the hub in Cape Town, has described it as the “single most exciting project in global public health.” A Canadian parliamentary committee recommended last week that Canada should boost its financial contribution to the hub.

Afrigen is focusing on mRNA (messenger RNA) vaccines, which use genetic code to teach the body’s cells how to make a protein that triggers antibodies from the immune system. This technology was the basis of the Moderna and Pfizer/BioNTech COVID-19 shots.

Afrigen’s vaccine process is based on Moderna’s, but the U.S.-based company refused to co-operate, so Afrigen simply reverse-engineered its own version, using information in the public domain, without copying the pharmaceutical giant’s exact technology.

Moderna eventually decided not to fight against Afrigen, and allowed its vaccine to be used for comparison tests. But it has taken out several patents in South Africa, sparking fears that it could some day take legal action when Afrigen develops vaccines for other diseases. “They know where the power sits – the power sits in the patent system that protects them,” Prof. Terblanche said.

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Last month, a coalition of more than 30 health and human-rights groups wrote to South African President Cyril Ramaphosa to ask him for legal safeguards to protect the mRNA technology hub. They said they are deeply worried that Moderna’s patents in the country will hinder the development of vaccines for low-income countries.

Meanwhile, a consultancy hired by BioNTech issued a report saying that the outlook for Afrigen’s project was “not favourable” and could “damage” the vaccine producers. It called for the project to be “terminated immediately” – a demand that the South African government has declined to obey.

“I was very sad about it,” Prof. Terblanche said. “But then I just thought, why should we let them drain our energy? So I said, ‘Ignore it.’” Today the relationship between Afrigen and the two big mRNA manufacturers is basically “non-existent,” she added.

Instead of working with the vaccine hub, Pfizer struck its own deal with a local company, the Biovac Institute, to produce its vaccine in South Africa. But the deal is only a “fill-and-finish” arrangement – for the final stage of production and bottling – which allows Pfizer to retain control.

Afrigen and its South African partner, Biovac, expect to manufacture mRNA vaccines in large quantities within about three years. The pandemic might be largely over by then, but the breakthrough in African mRNA vaccines has benefits that go far beyond the coronavirus, for diseases that have been neglected for decades.

Africa has always suffered from its lack of medical manufacturing and its reliance on high-priced imports. Prof. Terblanche, like many South Africans, recalls the early years of the HIV epidemic, when millions of Africans perished because the newly developed antiretroviral medicines were unaffordable. Later in her career, she watched as South Africa endured long delays in getting flu vaccines. “When COVID happened, we couldn’t get sufficient access to vaccines for six months,” she said. “I thought, no, not again. It reinforced for us that it’s time we establish manufacturing capacity – or we’ll see this happen again and again. It should have been done 20 years ago.”

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During the pandemic, the WHO believed that doses donated through COVAX, a global vaccine-sharing initiative, would meet the needs of low-income countries. But it soon became clear that the non-profit was far too slow in providing such assistance – largely because of hoarding in wealthy countries, which received 70 per cent of the vaccines produced by the world’s major pharmaceutical companies.

“Any failure that happened in COVAX happened because countries did not want to share, not because COVAX was badly designed,” WHO emergencies director Mike Ryan told a conference this month. “We failed because of the greed of the North, we failed because of the greed of the pharmaceutical industry, we failed because of self-interest in certain member states who were not prepared to share.”

African health agencies are pushing hard to escape such reliance on foreign corporations and organizations. Within 20 years, they want Africa to be producing 60 per cent of the vaccines that are used in the continent, up from 1 per cent today.

But, even now, Afrigen’s research is hampered by the difficulty in importing key ingredients, some of which are under patent control. “The frustration is that we’re waiting too long for equipment and raw materials,” Prof. Terblanche said. “Some suppliers don’t prioritize us.”

Funding for African companies has always been a challenge as well. She recalls a BioNTech consultant “snooping around” at Afrigen in its early days; he told her the company would struggle to raise capital for the project. She surprised him by disclosing that Afrigen had already managed to secure the money, because of the pledges from Canada and others. “It would have been impossible without it,” she said.

The vaccine hub is aiming to raise a further US$40-million for its budget, to train Afrigen’s global partner companies and to develop new vaccines for neglected diseases, Prof. Terblanche said.

“That’s what drives us: to address the unmet needs in low- and middle-income countries that the rest of the world is oblivious to and has forgotten about.”

What is an mRNA vaccine? How does it work?

For more than 25 years, research labs have been exploring the use of messenger RNA to build the body’s immunity against diseases. With the technology’s proven efficacy against the COVID-19 virus, researchers see a future in which the platform could be used to make vaccines and treatments for many more diseases, including malaria, tuberculosis, hepatitis B, cystic fibrosis and even HIV, for which human trials of an mRNA vaccine have already begun.

The vaccine is a Messenger RNA (mRNA) encased in a lipid envelope

1

mRNA

Envelope

Cell membrane

HOST

CELL

The vaccine enters in a compartment (an endosome) formed from the cell membrane

2

The endosome fuses with the lipid envelope and the mRNA is released. The mRNA carries the instructions for making copies of the virus’ spike proteins

3

Ribosomes, the cell’s protein builders, read the mRNA and produce a long chain of amino acids called a polypeptide

4

Ribosome

Polypeptides

The polypeptides assemble to form the viral spike proteins

5

Viral spike protein

ACE2 receptors

The cell displays the spike proteins to the immune system

6

Antibody

The immune system is primed to produce antibodies that prevent the virus from attaching to host cells via the ACE2 receptor

7

Virus

particle

MURAT YÜKSELIR /

THE GLOBE AND MAIL

For more than 25 years, research labs have been exploring the use of messenger RNA to build the body’s immunity against diseases. With the technology’s proven efficacy against the COVID-19 virus, researchers see a future in which the platform could be used to make vaccines and treatments for many more diseases, including malaria, tuberculosis, hepatitis B, cystic fibrosis and even HIV, for which human trials of an mRNA vaccine have already begun.

1

The vaccine is a Messenger RNA (mRNA) encased in a lipid envelope

mRNA

Envelope

Cell membrane

HOST CELL

2

The vaccine enters in a compartment (an endosome) formed from the cell membrane

3

The endosome fuses with the lipid envelope and the mRNA is released. The mRNA carries the instructions for making copies of the virus’ spike proteins

4

Ribosomes, the cell’s protein builders, read the mRNA and produce a long chain of amino acids called a polypeptide

Ribosome

Polypeptides

5

The polypeptides assemble to form the viral spike proteins

Viral spike protein

ACE2 receptors

6

The cell displays the spike proteins to the immune system

Antibody

7

The immune system is primed to produce antibodies that prevent the virus from attaching to host cells via the ACE2 receptor

Virus

particle

MURAT YÜKSELIR /

THE GLOBE AND MAIL

For more than 25 years, research labs have been exploring the use of messenger RNA to build the body’s immunity against diseases. With the technology’s proven efficacy against the COVID-19 virus, researchers see a future in which the platform could be used to make vaccines and treatments for many more diseases, including malaria, tuberculosis, hepatitis B, cystic fibrosis and even HIV, for which human trials of an mRNA vaccine have already begun.

Virus

particle

The vaccine is a Messenger RNA (mRNA) encased in a lipid envelope

The immune system is primed to produce antibodies that prevent the virus from attaching to host cells via the ACE2 receptor

1

7

mRNA

Envelope

ACE2

receptors

Antibody

Cell membrane

The cell displays the spike proteins to the immune system

6

HOST CELL

Viral spike protein

The polypeptides assemble to form the viral spike proteins

5

The vaccine enters in a compartment (an endosome) formed from the cell membrane

2

Polypeptides

The endosome fuses with the lipid envelope and the mRNA is released. The mRNA carries the instructions for making copies of the virus’ spike proteins

Ribosomes, the cell’s protein builders, read the mRNA and produce a long chain of amino acids called a polypeptide

3

4

MURAT YÜKSELIR / THE GLOBE AND MAIL

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