Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic. Abstract: Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime and are the cellular basis of vaccine durability and require the bone marrow (BM) microniche to sustain survival. In our lab, we have definitively linked the long-lived viral serum antibodies to the BM cellular compartment within the healthy human BM (CD19-CD38hiCD138+) PC subset thereby establishing the LLPC compartment. We have also developed in vitro BM microniche cultures that mimic the BM microenvironment to sustain PC survival. In this application, we plan (1) to develop a novel in vitro biomarker of vaccine durability using this novel in vitro BM mimic and to dissect the mechanisms of early blood ASC of long-lived vaccines, acute viral infections, compared to short-lived vaccines, (2) to identify the unique identity of LLPC precursors in the blood early after vaccination, and (3) to study mechanisms of LLPC generation in disease models of Systemic Lupus Erythematosis which is characterized by high levels of long-lived antibodies and an abundance of LLPC. In summary, these studies will distinguish the cellular and molecular programs of LLPC generation and maintenance after immunization.
Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic. Narrative: Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime and are the cellular basis of vaccine durability. LLPC require the bone marrow microniche to sustain survival, and systemic lupus erythematosus (SLE), an autoimmune disease, is characterized by high levels of long-lived antibodies. In this application, we plan (1) to develop a novel in vitro biomarker of human vaccine durability and to dissect the mechanisms of how early blood ASC of long-lived vaccines compare to short-lived vaccines, (2) to identify the unique identity of LLPC precursors in the blood, and (3) to study mechanisms of LLPC generation in disease models of SLE where there is an abundance of LLPC.
