Studying Viral Spike Proteins to Inform a Universal Coronavirus Vaccine

Coronaviruses (CoVs) are critical to research since they can be detrimental to global health and have caused three major epidemics in humans in the last 20 years. While the current vaccines against SARS-CoV-2, the virus which causes COVID-19, are highly effective, they are not well-suited for the wide range of variation that different CoVs can have. To better address this ongoing threat to global health, our group aims to design a universal CoV vaccine which could protect against multiple CoV strains. While most of the original SARS-CoV-2 vaccines targeted one part of the viral spike protein, we hypothesize a universal vaccine will be more effective by targeting multiple, well-conserved sites on the viral spike that are present on a range of virus strains. Dr. Corbett's team is well poised to study CoV vaccines due to their role in the development of the Moderna mRNA COVID-19 vaccine. For my project, I will study the structure of the SARS-CoV-2 viral spike protein and the human immune response to the protein, with the goal of informing a universal CoV vaccine. Specifically, I will determine the best domains on the spike protein to target for vaccination by studying how different antibodies (from previously infected people) can inhibit virus infection. The antibodies will be tested in combination and individually to determine what yields the highest level of protection against different CoVs. The specific binding sites of the antibodies will then be visualized through high resolution imaging to map the important sites for vaccine targets on the spike protein. Using this knowledge, our group will design optimized vaccine platforms in the lab to elicit enhanced immune responses against these sites and improved vaccine efficacy. This work will be initially done in mice models, with the long-term goal of reaching clinical trials in humans. If successful, this cross-reactive vaccine strategy could also be applied to other viral pathogens with pandemic potential.