Project Summary Live attenuated vaccinations generate both humoral and cellular immune memory, accounting for much of the increased duration of protective immune memory. As increased protective immune memory to live attenuated vaccines is of critical importance, understanding the mechanisms of this increased protective immune memory is essential to improve current vaccines. To this end, we and others have demonstrated that antigens derived from infectious viral infections persist in the host for extended periods of time, well beyond the time in which the infection is cleared from the host. Our lab has specifically identified that antigens derived from both vaccination and viral infections persist or are archived by the host lymphatic endothelial cells LECs, identifying the source of archived antigens. We have published that this archived antigen maintains a more effector like pool of antigen specific memory cells which enhances the clearance of a secondary infectious challenge. Thus, identification of key mechanisms involved in antigen archiving during vaccination is critical for our understanding of enhanced protective immunity to vaccination. To better understand the mechanisms of antigen archiving we have developed a “molecular tracking device” that leverages single-cell mRNA sequencing to track the distribution, acquisition, and retention of antigen in the lymph node and other organs. This project will elucidate the unique mechanisms behind antigen archiving, how multiple un-related infections contribute to the kinetics of archived antigens and memory boosting, and the potential cell types in other tissues that may also contribute to antigen archiving.

Project Narrative In this proposal we aim to use a vaccine regimen with a unique tracking device to understand the kinetics of antigen archiving and the cell types required. These studies will identify mechanisms involving the uptake, retention and release of antigens and the functional outcomes associated with these processes.