This is a historic moment,” said WHO director-general Tedros Adhanom Ghebreyesus in a statement that month.
The vaccine — dubbed RTS,S — promises a 30 percent reduction in severe malaria in fully vaccinated children. In 2020, a research team estimated that each year, the vaccine could prevent between 3 and 10 million malaria cases, and save the lives of 14,000 to 51,000 small children, depending on how it’s implemented.
What those plaudits often failed to note, though, was that the core ingredient of the path-breaking vaccine was actually almost 35 years old — and that researchers have known since the late 1990s that the formula was probably somewhat effective at protecting against malaria.At a time when Covid-19 vaccines were developed and authorized in less than one year, the delay for malaria raises a question: Why did a vaccine for a leading global killer take so long to arrive? According to researchers involved in the development of RTS,S, the answer involves the challenges of developing a vaccine against a vexing parasite — and the chronic lack of urgency and funding behind malaria research, which stymied the logistics of research trials at every step.
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The people who are affected by malaria, “they’re not Europeans, they’re not Australians, they are poor African children,” said Ashley Birkett, director of the malaria vaccine initiative at PATH, a non-profit global health organization. “Unfortunately, I think we have to accept that that is part of the reason for the lack of urgency in the community.”
Researchers had been searching for a malaria vaccine since the late 1960s. In 1980, they identified a protein that is abundant on the parasite’s surface, called circumsporozoite protein, and realized that a vaccine directed against this protein might grant immunity. After U.S. government researchers sequenced the gene for the protein in 1984, the military asked them to develop a malaria vaccine to protect troops overseas. Government officials then enlisted Smith, Kline & French, a precursor company to the pharmaceutical giant GlaxoSmithKline, to help.
The work, experts recalled, was extremely challenging. The malaria parasite has a notoriously complex life cycle with at least three distinct stages once it’s inside humans, and it is “actually changing clothes during the evolution, during the cycle,” said Lode Schuerman, the scientific affairs director for GSK’s global health vaccines program. Any vaccine developed against a particular stage would have to stop the infection then, and would not work if the parasite has advanced to the next stage. Moreover, basic tools that researchers use today to speed up vaccine development did not yet exist.
More than a dozen attempted vaccines based on the circumsporozoite protein failed. The exception was RTS,S. In the late 1980s and early 1990s, the team figured out various technical details, and a 1998 trial in Gambia, involving 250 men, found that the vaccine prevented 34 percent of infections.
“That was really the start of RTS,S,” said Brian Greenwood, an infectious disease expert at the London School of Hygiene and Tropical Medicine who was involved in the Gambia trial.
Still, attention to the vaccine, Greenwood recalled, was driven more by intellectual interest than a sense of medical urgency — at least for the broader public, beyond American troops. “I don’t think there was any sort of push. It was done by people who were more academics and interested in the immunology,” he said. “It wasn’t seen as a public health issue.”
And, people involved in the vaccine’s development told Undark, the promising shot was about to run into a whole new set of problems: the myriad tribulations that come with testing a vaccine that doesn’t have
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