(392c) Harnessing Biomaterials to Study and Engineer Lymph Node Function

Vaccines and immunotherapies have generated some of the largest impacts on human health in history, but a fundamental challenge now facing the field is how to direct the specific properties of immune responses that are elicited. This idea of tuning response is termed â??immunomodulationâ?, and is critical in designing more efficacious and specific vaccines and immunotherapies. In this seminar I will discuss two strategies we are developing to study and exploit the interactions between biomaterials and immune cells and tissues. One approach involves direct delivery of synthetic vaccine carriers to lymph nodes, key tissues that coordinate immune response. We have combined direct lymph node injection with biomaterials to establish a platform to study the link between local lymph node function and systemic immunity by probing the roles of signal density and material properties. In addition to these ideas, we are exploiting directed delivery for therapeutic vaccination in the areas autoimmunity and cancer. The second focus area is the design of new modular materials we have created using polyionic immune signals to form stable vaccine capsules. These immune polyelectrolyte multilayers (iPEMs) are self-assembled entirely from antigens and adjuvants to allow selective activation of pro-inflammatory signaling pathways without other carrier components such as polymers or lipids. In mice, iPEMs injected along traditional vaccination routes enhance the function of dendritic cells in draining lymph nodes, potently expand antigen-specific T cells against antigens used to build iPEMs, and provide protection during tumor challenge. Ultimately, these strategies could contribute to better understanding of the interactions between biomaterials and the immune system, and improve the rational design of materials that serve not only as carriers, but also as agents that actively direct immune response.