How the leading coronavirus vaccines made it to the finish line - The Washington Post - 0 views
-
If, as expected in the next few weeks, regulators give those vaccines the green light, the technology and the precision approach to vaccine design could turn out to be the pandemic’s silver linings: scientific breakthroughs that could begin to change the trajectory of the virus this winter and also pave the way for highly effective vaccines and treatments for other diseases.
-
Vaccine development typically takes years, even decades. The progress of the last 11 months shifts the paradigm for what’s possible, creating a new model for vaccine development and a toolset for a world that will have to fight more never-before-seen viruses in years to come.
-
Long before the pandemic, Graham worked with colleagues there and in academia to create a particularly accurate 3-D version of the spiky proteins that protrude from the surface of coronaviruses — an innovation that was rejected for publication by scientific journals five times because reviewers questioned its relevance.
- ...26 more annotations...
-
Messenger RNA is a powerful, if fickle, component of life’s building blocks — a workhorse of the cell that is also truly just a messenger, unstable and prone to degrade.
-
That same year, a team at the University of Wisconsin startled the scientific world with a paper that showed it was possible to inject a snippet of messenger RNA into mice and turn their muscle cells into factories, creating proteins on demand.
-
If custom-designed RNA snippets could be used to turn cells into bespoke protein factories, messenger RNA could become a powerful medical tool. It could encode fragments of virus to teach the immune system to defend against pathogens. It could also create whole proteins that are missing or damaged in people with devastating genetic diseases, such as cystic fibrosis.
-
In 2005, the pair discovered a way to modify RNA, chemically tweaking one of the letters of its code, so it didn’t trigger an inflammatory response. Deborah Fuller, a scientist who works on RNA and DNA vaccines at the University of Washington, said that work deserves a Nobel Prize.
-
messenger RNA posed a bigger challenge than other targets.“It’s tougher — it’s a much bigger molecule, it’s much more unstable,”
-
Unlike fields that were sparked by a single powerful insight, Sahin said that the recent success of messenger RNA vaccines is a story of countless improvements that turned an alluring biological idea into a beneficial technology.
-
“This is a field which benefited from hundreds of inventions,” said Sahin, who noted that when he started BioNTech in 2008, he cautioned investors that the technology would not yield a product for at least a decade. He kept his word: Until the coronavirus sped things along, BioNTech projected the launch of its first commercial project in 2023.
-
“It’s new to you,” Fuller said. “But for basic researchers, it’s been long enough. . . . Even before covid, everyone was talking: RNA, RNA, RNA.”
-
All vaccines are based on the same underlying idea: training the immune system to block a virus. Old-fashioned vaccines do this work by injecting dead or weakened viruses
-
ewer vaccines use distinctive bits of the virus, such as proteins on their surface, to teach the lesson. The latest genetic techniques, like messenger RNA, don’t take as long to develop because those virus bits don’t have to be generated in a lab. Instead, the vaccine delivers a genetic code that instructs cells to build those characteristic proteins themselves.
-
Severe acute respiratory syndrome had emerged in 2003. Middle East respiratory syndrome (MERS) broke out in 2012. It seemed clear to Graham and Jason McLellan, a structural biologist now at the University of Texas at Austin, that new coronaviruses were jumping into people on a 10-year-clock and it might be time to brace for the next one.
-
That infection opened Graham’s eyes to an opportunity. HKU1 was merely a nuisance, as opposed to a deadly pneumonia; that meant it would be easier to work with in the lab, since researchers wouldn’t have to don layers of protective gear and work in a pressurized laboratory.
-
They wanted the immune system to learn to recognize the thumb tack spike, so McLellan tasked a scientist in his laboratory with identifying genetic mutations that could anchor the protein into the right configuration. It was a painstaking process for Nianshuang Wang, who now works at a biotechnology company, Regeneron Pharmaceuticals. After trying hundreds of genetic mutations, he found two that worked. Five journals rejected the finding, questioning its significance, before it was published in 2017.
-
Last winter, when Graham heard rumblings of a new coronavirus in China, he brought the team back together. Once its genome was shared online by Chinese scientists, the laboratories in Texas and Maryland designed a vaccine, utilizing the stabilizing mutations and the knowledge they had gained from years of basic research — a weekend project thanks to the dividends of all that past work.
-
Graham needed a technology that could deliver it into the body — and had already been working with Moderna, using its messenger RNA technology to create a vaccine against a different bat virus, Nipah, as a dress rehearsal for a real pandemic. Moderna and NIH set the Nipah project aside and decided to go forward with a coronavirus vaccine.
-
On Jan. 13, Moderna’s Moore came into work and found her team already busy translating the stabilized spike protein into their platform. The company could start making the vaccine almost right away because of its experience manufacturing experimental cancer vaccines, which involves taking tumor samples and developing personalized vaccines in 45 days.
-
At BioNTech, Sahin said that even in the early design phases of its vaccine candidates, he incorporated the slight genetic changes designed in Graham’s lab that would make the spike look more like the real thing. At least two other companies would incorporate that same spike.
-
If all goes well with regulators, the coronavirus vaccines have the makings of a pharmaceutical industry fairy tale. The world faced an unparalleled threat, and companies leaped into the fight. Pfizer plowed $2 billion into the effort. Massive infusions of government cash helped remove the financial risks for Moderna.
-
But the world will also owe their existence to many scientists outside those companies, in government and academia who pursued ideas they thought were important even when the world doubted them
-
“They’re using the technology that [Kariko] and I developed,” he said. “We feel like it’s our vaccine, and we are incredibly excited — at how well it’s going, and how it’s going to be used to get rid of this pandemic.”
-
As executives become billionaires, many scientists think it is fair to earn money from their inventions that can help them do more important work. But McLellan’s laboratory at the University of Texas is proud to have licensed an even more potent version of their spike protein, royalty-free, to be incorporated into a vaccine for low and middle income countries.
-
Some of those scientists will receive remuneration, since their inventions are licensed and integrated into the products that could save the world.
-
“People hear about [vaccine progress] and think someone just thought about it that night. The amount of work — it’s really a beautiful story of fundamental basic research,” Fauci said. “It was chancy, in the sense that [the vaccine technology] was new. We were aware there would be pushback. The proof in the pudding is a spectacular success.”
-
The Vaccine Research Center, where Graham is deputy director, was the brainchild of Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. It was created in 1997 to bring together scientists and physicians from different disciplines to defeat diseases, with a heavy focus on HIV.
-
the pandemic wasn’t a sudden eureka moment — it was a catalyst that helped ignite lines of research that had been moving forward for years, far outside the spotlight of a global crisis.