Jason McLellan

McLellan led a team from The University of Texas at Austin and the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center that produced the first molecular structure, or 3D atomic scale map, of the novel coronavirus’ spike protein, the protein that allows the virus to attach to and infect host cells.[4] The results were published online on February 19, 2020 in Science,[13] one of the world's top academic journals, and was highlighted on the cover of the 13 March 2020 print edition.[14]

The molecular structure provides a blueprint for scientists to learn to disrupt these processes through developing new treatments or vaccines.[15] Aubree Gordon, an associate professor of epidemiology at the University of Michigan who was not a part of the study was quoted by LiveScience as saying: "It's a very important step forward and may help in the development of a vaccine against SARS-COV-2."[15]

According to Google Scholar, as of August 13, 2020, the Science paper revealing the spike protein structure had already been cited by 1675 subsequent scientific papers.[2] The achievement was also highlighted as an important step towards a vaccine by the director of the National Institutes of Health, Francis Collins, in the NIH Director's Blog.[16]

McLellan and his team collaborated with researchers at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center to design a stabilized version of the SARS-CoV-2 spike protein,[4][5] called S-2P or 2P, which biotechnology company Moderna used as the basis for the vaccine candidate mRNA-1273,[7][8][9][10] the first COVID-19 vaccine candidate to enter phase I clinical trials in the U.S.[11] The UT Austin and NIH teams filed a joint patent application on the mutated spike protein.[17]

Moderna’s vaccine candidate, mRNA-1273, contains the genetic code for the stabilized version of the spike protein.[8] When a person is vaccinated with mRNA-1273, their own cells should theoretically produce these modified spike proteins, triggering their immune systems to develop antibodies against the actual coronavirus.[18]

The SARS-CoV-2 spike protein takes on one shape before entering a cell and another shape after, known as the prefusion and postfusion conformations.[19] Antibodies that recognize spike proteins in the prefusion shape are much more effective at preventing infection than antibodies that recognize spike proteins in the postfusion shape.[19] McLellan—along with his team members Daniel Wrapp and Nianshuang Wang, plus Barney Graham and Kizzmekia Corbett at NIAID's Vaccine Research Center—engineered the spike protein to stay in its initial shape so it can be recognized.[13] This, combined with Moderna's technology that uses messenger RNA to encode information about the virus, allows mRNA-1273 to trigger an immune response in vaccinated subjects.[8]

The stabilized spike protein developed by McLellan and his colleagues forms the basis of four COVID-19 vaccine candidates in clinical trials in the U.S.[5][12]

McLellan and his team worked with pharmaceutical company Eli Lilly and Company to develop their monoclonal antibody treatment bamlanivimab (LY-CoV555),[20] which received emergency use authorization from the U.S. Food and Drug Administration in November 2020.[21]

In a separate but related project, McLellan and Daniel Wrapp worked with colleagues at the NIAID Vaccine Research Center and Ghent University to develop an antibody therapy for COVID-19 based on antibodies produced by a llama.[22] Initial tests indicate that their antibody blocks viruses that display the SARS-CoV-2 spike protein from infecting cells in culture. They reported their findings in Cell on May 5, 2020.[23] As of May 2020, the team was preparing to conduct preclinical studies in animals such as hamsters or nonhuman primates, with the hopes of next testing in humans.[24]

Jason McLellan was one of seven researchers honored with a 2020 Golden Goose Award from the American Association for the Advancement of Science in recognition of his COVID-19 research.[25][22] He was the 2020 recipient of the William Prusoff Memorial Award from the International Society for Antiviral Research, which honors a young scientist who has shown excellence in antiviral research and promise for future contributions to the field.[26] Previous honors include the Norman P. Salzman Memorial Award in Virology (2012),[27] the Charles H. Hood Foundation Child Health Research Award (2015),[28] the American Crystallographic Association Etter Early Career Award (2018)[29] and the Viruses Young Investigator in Virology Prize (2019).[30]