The Corey Lab investigates the underlying mechanisms between herpes simplex virus pathogenesis and the host immune response; specifically, the associations between HSV-2 disease severity and the quantity, quality and diversity of tissue resident memory CD4+ and CD8+ T cells that persist after HSV-2 reactivation in humans. The ultimate goal is to develop an immunotherapeutic vaccine to control subclinical HSV-2 reactivation and reduce the transmission to sexual partners.
We utilize laboratory-based, clinical and mathematical modeling techniques to better define the cellular immunology of HSV. Our lab has developed an innovative method for measuring in vivo how host pathogen interactions change over the course of infection using sequential skin biopsies from HSV-2 infected cohorts.
The use of cell type-specific immunofluorescent staining and laser capture microdissection (LCM) methodologies allows one to capture and enrich for a specific cell type from a diverse and complex tissue milieu and then proceed to immediately analyze these cell populations without in vitro manipulation. These studies have shown that immune control of HSV lies in the peripheral skin and mucosa and that a unique type of CD8+ T cell is involved in containing virus at the portal of neuronal release of reactivating virus. The lab has also developed and refined an elegant mathematical model for the spatial and temporal dynamics of the interaction between virus and host and has redefined our understanding of the spatial dynamics between resident host memory T cells and viral replication that controls whether viral shedding will lead to a symptomatic episode or silent reactivation.