My research group intends to design a vaccine that is effective against the coronaviruses that cause Middle East Respiratory Syndrome (MERS) and severe acute respiratory syndrome (SARS). Coronaviruses, which cause a variety of respiratory infections, use a trimeric spike protein to gain entry into human cells and initiate infection. The spike protein is also the virus’s Achilles’ heel, serving as a target for neutralizing antibodies produced by the host immune system. Recently, I leveraged methodological developments in cryo-electron microscopy to determine for the first time the precise, three-dimensional architecture of a coronavirus spike protein. Combining this approach with other cutting-edge methods in immunology, molecular biology, and protein design, I will characterize the structures of the spike proteins from the MERS-CoV, SARS-CoV, and other coronaviruses to understand host adaptation and identify epitopes that could be targeted by neutralizing antibodies. Based on this information, I will engineer and test vaccine candidates designed to elicit a vigorous immune response—work that could represent a major advance in treating these human infections for which there are currently no approved antivirals or vaccines.