Headquarters of the Bill and Melinda Gates Foundation in Seattle.
| Photo Credit: AP

A $40 million investment will help several African manufacturers produce new messenger RNA vaccines on the continent where people were last in line to receive jabs during the COVID-19 pandemic, the Bill and Melinda Gates Foundation announced Monday.

While it could still take at least three more years before any of the vaccines are approved and on the market, the foundation said that its mRNA investment marks an important step forward in improving vaccine equity.

“Whether it’s for local diseases in Africa like Rift Valley (fever) or for global diseases like TB, mRNA looks like a very promising approach,” Bill Gates told The Associated Press on Sunday after visiting one of the facilities involved, the Institut Pasteur in Dakar, Senegal.

“And so it allows us to bring in lots of African capabilities to work on these vaccines, and then this can be scaled up.”

The announcement comes as the foundation opens its annual three-day Grand Challenges event, which brings together scientists and public health researchers from around the world.

Institut Pasteur, along with the South Africa-based company Biovac, will be using an mRNA research and manufacturing platform that was developed by Quantoom Biosciences in Belgium.

The two Africa-based vaccine manufacturers are receiving $5 million each in funding from the foundation, while another $10 million is earmarked for other companies that have not yet been named.

The remaining $20 million is going to Quantoom “to further advance the technology and lower costs.”

The mRNA vaccine technology came to the forefront with the production of COVID-19 vaccines made by Pfizer and Moderna.

The messenger RNA approach starts with a snippet of genetic code carrying instructions for making proteins. And by picking the right virus protein to target, the body turns into a mini vaccine factory.

Those COVID-19 mRNA vaccines were fast-tracked through the regulatory process and granted emergency use authorisation.

The new vaccines under development in Africa face a far longer development timeline — anywhere from three to seven years.

Dr. Amadou Sall, chief executive officer at Institut Pasteur, said the deal will help build vaccine self-reliance in Africa.

The institute already has been producing yellow fever jabs since the 1930s and now hopes mRNA technology can be harnessed to produce vaccines for diseases endemic on the continent like Lassa fever, Rift Valley fever and Crimean-Congo hemorrhagic fever.

“What we want is next time there is a pandemic — we hope it won’t happen soon — Africa would be able to make its own vaccine, to contribute to the development, and make sure that we protect the population,” Mr. Sall said.

“What happened with COVID should never happen again in the sense that Africans should get vaccinated as a matter of equity.”

Jose Castillo, chief executive officer of Quantoom Biosciences, said the mRNA technologies allow low- and middle-income countries “to become autonomous in terms of research and development.”

The platform only needs 350 square metres (3,800 square feet) of space to have a manufacturing facility capable of making tens of millions of doses.

“Many people in many countries did not have the access they would have needed for them to be vaccinated on time” during the COVID-19 pandemic, he said.

“So we think that this technology will have a tremendous impact in terms of autonomy through regional manufacturing.”

With $8.3 billion to give away in 2023, the Gates Foundation is the largest private philanthropic donor.

And with an endowment of more than $70 billion, its spending power is likely to continue for many decades.

It has spent billions of dollars to vaccinate against polio, treat and prevent malaria and HIV and more recently advance vaccines for diseases like cholera.

Penn Medicine scientists Katalin Kariko and Drew Weissman have been awarded the 2023 Nobel Prize in Physiology or Medicine for discoveries enabling the development of mRNA vaccines.
| Photo Credit: Peggy Peterson/Penn Medicine, Reuters

The 2023 Nobel Prize for physiology or medicine has been awarded to the Hungarian biochemist Katalin Karikó and the American physician-scientist Drew Weissman. According to the Royal Swedish Academy of Science,  they have been feted for “discoveries concerning nucleoside base modification that enabled the development of effective mRNA vaccines against COVID-19”.

Dr. Karikó is only the thirteenth woman to win the prize.

That the citation mentions the pandemic is testament to the effect mRNA vaccines had on its evolution as well as how the global disaster became an opportunity for these vaccines’ technology to showcase its potential.

mRNA stands for messenger RNA, a type of molecule that carries instructions from the DNA to a cell’s cytoplasm, where those messages are ‘read’ to produce various proteins. In the late 1980s, scientists realised that mRNA could become the basis for a new kind of vaccines if some hurdles could be overcome.

The idea was to inject the body with a modified mRNA that would instruct cells to build a certain protein, which could then provoke the body’s immune system to ‘attack’ it as well as prepare itself to encounters with the same protein in future. This protein could be something produced by a virus – such as the spike protein of SARS-CoV-2. But the mRNA would have to survive its journey inside the body and be able to enter a cell.

Dr. Karikó and Dr. Weissman began to collaborate in the late 1990s. They and other scientists published many studies until 2004 elucidating the steps from delivering mRNA into a body (such as of a rat) to the immune system responding. But one problem remained. The immune system sensed the synthetic mRNA to be a foreign substance that needed to be eliminated but not the cells’ mRNA. Why?

A study the duo published in 2005, with Michael Buckstein and Houping Ni, had the answer: the cells’ mRNA underwent chemical reactions that modified it in certain ways, whereas the synthetic mRNA remained unchanged.

RNA is made up of smaller molecules called bases. Dr. Karikó and Dr. Weissman reported that when they modified some of these bases in the synthetic mRNA and delivered it to cells, the cells produced more provocative proteins than they did without the modifications. They had found out how foreign mRNA could enter a body and then its cells without setting off alarm bells.

They published two more studies that set the stage for the use of an mRNA platform for a new kind of vaccine. In 2020, the COVID-19 pandemic dawned on the world, and mRNA vaccines played a pivotal role – if also one overtaken by the dubious virtues of vaccine nationalism – in lowering its death toll.

“You can start a production cycle in the morning and by evening have enough for tests,” former Indian Institute of Science, Bengaluru, director Govindarajan Padmanabhan told The Hindu in October 2022 about the advantage of mRNA vaccines. Currently, scientists are exploring their use against influenza, dengue, and some cancers and auto-immune diseases.

Dr. Drew Weissman arrives for the Ninth Breakthrough Prize Ceremony at the Academy Museum of Motion Pictures in Los Angeles, California, U.S., April 15, 2023.
| Photo Credit: Reuters

Drew Weissman’s decades of research into mRNA technology paved the way for Covid-19 vaccines, finally earning a Nobel prize for the physician-scientist.

The 64-year-old University of Pennsylvania immunologist, who won the Nobel Medicine Prize along with long-time collaborator Katalin Kariko on Monday, is far from done.

His next quests include, among others, developing a vaccine against all future coronaviruses.

“There have been three (coronavirus) pandemics or epidemics in the past 20 years,” Weissman told AFP recently, referring to the original SARS virus, MERS and Covid-19.

“You have to assume there’s going to be more, and our idea was that we could wait for the next coronavirus epidemic or pandemic, and then spend a year and a half making a vaccine. Or we could make one now.”

Twin breakthroughs

The world is now aware of the elegance of the mRNA (messenger ribonucleic acid) vaccines, that deliver genetic instructions to cells telling them to recreate the spike protein of the coronavirus, in order to trigger effective antibodies when they encounter the real thing.

But back when Weissman teamed up with Kariko in the 1990s, the research was considered a scientific dead-end, and working with DNA was considered a more promising avenue.

“We started working together in 1998, and that was without much funding and without much in the way of publications,” he said.

In 2005, the pair found a way to alter synthetic RNA to stop it from causing a massive inflammatory response found in animal experiments.

“Just before our paper was published, I said ‘Our phones are going to ring off the hook,'” he recalls.

“We sat there staring at our phones for five years, and they never rang!”

With a second big breakthrough in 2015, they found a new way to deliver the particles safely and effectively to their target cells, using a fatty coating called “lipid nanoparticles.”

Both developments are part of the Pfizer and Moderna Covid-19 vaccines today.

Helping people

Weissman grew up in Lexington, Massachusetts.

His father and mother, both since retired, were an engineer and dental hygienist, respectively.

“When I was five years old, I was diagnosed as a type-one diabetic, and back then it was testing urine and taking insulin shots a few times a day,” he recalled, and this motivated him to pursue science.

He was educated at Brandeis University and completed an MD-Phd program in immunology at Boston University.

As a young fellow at the National Institutes of Health, he worked for several years in Anthony Fauci’s lab on HIV research, before finally arriving at his long-time home Penn.

Weissman was a practicing doctor until a few years ago, and says it brings him great joy that his invention has helped save millions of lives.

“I’m a clinician scientist, my dream since starting college and medical school was to make something that helps people. I think I can say that I’ve done that. So I am incredibly happy,” he said.

Beyond vaccines, mRNA technology is also being heralded for its potential across medicine.

Weissman’s team is working on using RNA to develop a single-injection gene therapy to overcome the defect that causes sickle cell anemia, a genetic blood disease that 200,000 babies are born with in Africa every year.

Significant technical challenges remain to ensure the treatment is able to correctly edit genes and is safe, but the researchers are hopeful.

Bone marrow transplant, an expensive treatment with serious risks, is currently the only cure.