A gamble pays off in ‘spectacular success’: How the leading coronavirus vaccines made it to the finish line

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. Since 1961, scientists had known about messenger RNA, the transient genetic material that makes life possible, taking the instructions inscribed in DNA and delivering those to the protein-making parts of the cell. 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. Ugur Sahin, chief executive of BioNTech, said it was thrilling when he and colleagues in 2016 developed a nanoparticle to deliver messenger RNA to a special cell type that could take the code and turn it into a protein on its surface to provoke the immune system. 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. Scientists have to choose which telltale part of the virus to show the immune system. Long before the pandemic, Graham’s research had revealed that some virus proteins change shape after they break into a person’s cells. A vaccine based on the wrong shape could effectively train the immune system to be an ineffective sheriff, never stopping vandals or burglars before they wreak their havoc. Graham had used this insight to design a better vaccine against respiratory syncytial virus; it made Science magazine’s shortlist of 2013’s most important scientific breakthroughs. Coronaviruses seemed like an important next target. 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 that it might be time to brace for the next one. 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. On Jan. 13, Moderna, 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. 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. 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. Graham is matter-of-fact, rather than exuberant, and quickly changes the subject to the immense amount of work that remains to be done. Historic scientific news must now be transformed into a tool that is mass produced, distributed and used widely around the world to blunt the sickness and suffering of this winter — and to lift the pall this pandemic has cast over virtually every aspect of daily life. He recalled that his 5-year-old granddaughter recently heard the family talking about “getting back to normal” if a vaccine is successful. “She looked up and said, ‘What is normal life, what do you mean by that?’ ” Graham said. “Half of her memorable life has been like this.” https://www.washingtonpost.com/health/2020/12/06/covid-vaccine-messenger-rna/