The Plague Year | The New Yorker

February 14, 2021

Nice discussion on the mistakes on aerosols + a vaccine development chronology

During the study’s initial stages, in February and March, the researchers were discomfited by the implications of their data. “The rapidity and degree of spread suggested it wasn’t a series of one-to-one-to-one transmissions,” Dr. Jacob Lemieux, a lead author, told me. Rather, it was “one-to-many transmission events.” That raised the question of airborne transmission. “At the time, the idea was heretical,” Lemieux said. “We were afraid to consider it, because it implied a whole different approach to infection control”—one in which masks played a central role, especially indoors. But the W.H.O. had repeatedly proclaimed that large respiratory droplets—as from a sneeze or a cough—drove the spread. This wasn’t based on data about the new virus, Lemieux said: “It was received wisdom based on how previous respiratory viruses had behaved. The global public-health
infrastructure has egg on its face. There’s a component of human nature that, until you get burned, you don’t know how hot the fire is.”

Until recently, one of the main imaging tools used by vaccinologists, the cryogenic electron microscope, wasn’t powerful enough to visualize viral proteins, which are incredibly tiny. “The whole field was referred to as blobology,” McLellan said. As a work-around, he developed expertise in X-ray crystallography. …McLellan showed me an “atomistic interpretation” of the F protein on the RSV virus—the visualization looked like a pile of Cheetos. It required a leap of imagination, but inside that murky world Graham and McLellan and their team manipulated the F protein, essentially by cloning it and inserting mutations that kept it strapped down. McLellan said, “There’s a lot of art to it.”

In 2013, Graham and McLellan published “Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus,” in Science, demonstrating how they had stabilized the F protein in order to use it as an antigen—the part of a vaccine that sparks an immune response. Antibodies could now attack the F protein, vanquishing the virus. Graham and McLellan calculated that their vaccine could be given to a pregnant woman and provide enough antibodies to her baby to last for its first six months—the critical period. The paper opened a new front in the war against infectious disease. In a subsequent paper in Science, the team declared that it had established “clinical proof of concept for structure-based vaccine design,” portending “an era of precision vaccinology.”

Within a day after Graham and McLellan downloaded the sequence for sars-CoV-2, they had designed the modified proteins. The key accelerating factor was that they already knew how to alter the spike proteins of other coronaviruses. On January 13th, they turned their scheme over to Moderna, for manufacturing. Six weeks later, Moderna began shipping vials of vaccine for clinical trials. The development process was “an all-time record,” Graham told me. Typically, it takes years, if not decades, to go from formulating a vaccine to making a product ready to be tested: the process privileges safety and cost over speed.

After the vaccine was tested in animals, it became clear that Graham’s design choices had been sound. The first human trial began on March 16th. A week later, Moderna began scaling up production to a million doses per month.