About Jason’s work
Jason McLellan is a structural biologist who studies viral fusion proteins and develops new treatments to prevent infectious diseases. McLellan’s engineered viral proteins are particularly important in catalyzing the design of vaccines against infectious respiratory diseases.
Viruses infect the host by using proteins on their surface to fuse with and invade the host’s cells. These fusion proteins are desirable targets for vaccines because inactivating them can prevent infection. However, the structure of fusion proteins varies greatly over time, making them difficult to isolate and target. In his initial work, McLellan used X-ray crystallography to describe the atomic-level structure (or conformation) of the respiratory syncytial virus (RSV) fusion protein for the first time. RSV can cause serious infections in infants and the elderly, but a vaccine has not been developed for over 50 years. McLellan found that one of the specific pre-fusion forms he had mapped was strongly antigenic, meaning it elicited a strong antibody response in the human immune system. He also discovered that incorporating amino acid changes into specific sites in the protein structure locks the protein into its antigenic configuration and prevents structural fluctuations. McLellan’s engineered protein became the basis for the first successful RSV vaccine. He continued to develop this structure-based approach to vaccine design in his work on coronaviruses that cause the common cold and Middle East Respiratory Syndrome (MERS). McLellan demonstrated that two proline residues, a type of amino acid, can stabilize the structure of the coronavirus spike protein before fusion. This work allowed McLellan to act quickly when the SARS-CoV-2 virus, which causes COVID-19, emerged in early 2020. His lab designed a stabilized, antigenic version of the SARS-CoV-2 spike protein just weeks after the virus’ genetic sequence was released. Their stabilized protein sequences are used in all COVID-19 vaccines approved for use in the United States. The vaccine triggers our immune system to produce antibodies against the stabilized spike protein, training it to recognize and deactivate future viruses.
McLellan’s team is currently focused on developing a universal vaccine that is effective against all coronaviruses. They identified the stem of the viral spike protein as a possible antigen and characterized several antibodies that react across the coronavirus family. He is also investigating the potential application of structure-based vaccine design to surface proteins of emerging viruses and bacterial pathogens. McLellan’s insights into protein structure, function and engineering are critical to protecting human health from the continued emergence of new infectious diseases.
