The second main area of progress in protein design has to do with self-assembly—the creation of small proteins that join together to make something larger. Here, too, I.P.D. has made a contribution. In a paper published in Science, in 2016, Baker’s lab reported the development of a protein-based icosahedron—a twenty-sided geometric shape, like a die for Dungeons & Dragons. The icosahedron was built from twenty “trimers” and twelve “pentamers”—proteins made of three and five smaller proteins, respectively. The component proteins had been built by bacteria, according to DNA instructions; they were then dissolved in a solution and, while floating around, joined together of their own accord, to create the symmetrical forms that Rosetta had predicted. A protein with such a shape—which is easy to build and roomy inside, with many useful vertices—could carry medicinal cargo through the body; it could also be studded with bits of virus, and, therefore, become a vaccine. (Immunologists have found that, when antigens form a repeating pattern—as they would on the surface of an icosahedron—they tend to stimulate a stronger immune response.)
Last year, Neil King’s lab at the I.P.D. produced such a vaccine: an icosahedron, or “nanoparticle,” arrayed with proteins from respiratory syncytial virus (R.S.V.), the leading cause of infant mortality after malaria. In animals, the new vaccine was ten times as effective as one in which viral proteins floated freely, on their own. A spinoff company, Icosavax, is now developing the R.S.V. vaccine further, with fifty-one million dollars in Series A financing; King, who was a postdoc in Baker’s lab and now leads the I.P.D.’s vaccine efforts, advises Icosavax. (Both he and Baker retain ownership stakes.) He is also working with the National Institutes of Health to use the same technology for a universal flu vaccine and a vaccine for sars-CoV-2. Last month, on the Web site bioRxiv, he posted a “preprint”—a paper that has not yet been peer-reviewed—on the first sars-CoV-2 results. The lab had vaccinated mice with a self-assembling protein nanoparticle on which sixty copies of the key part of the coronavirus’s spike protein had been embedded; in response, the mice produced ten times as many antibodies as they’d made when given a vaccine containing spike proteins alone. The antibodies made in response to the nanoparticle were also more powerful: they targeted multiple spots on the spike.