Mapping and Enhancing mRNA Vaccine Delivery & Immune Activation for SARS-CoV-2

The COVID-19 pandemic caused by the virus SARS-CoV-2 is the deadliest pandemic of the 21st century. Despite well-documented evidence that COVID-19 vaccines are safe and effective, the exact ways through which the contents of the vaccine are carried from the muscle where they are injected to the lymph nodes where a protective immune response is generated, is not fully understood. COVID-19 vaccines contain a genetic sequence from the virus called mRNA, contained in small lipid particles. We will use cutting-edge techniques to visualize the specific cells in muscle tissue that take up these mRNA-containing particles and their migratory pathway to lymph nodes, which is still unclear. Additionally, we will determine the genes they express at each stage, and identify the immune cells they interact with. Finally, we will assess new mRNA vaccine formulations to determine the most effective formulation that provides protection against SARS-CoV-2. We will start in animal models of disease and establish the necessary groundwork prior to clinical trials with human patients. This research will help us improve the effectiveness of current COVID-19 vaccines and inform development of all mRNA-based vaccines for the future.