Vaccines and immunotherapies have generated some of the largest impacts on human health in history, but a challenge facing the field is how to direct the specific properties of immune responses that are elicited. This talk will highlight two strategies we are developing to study and exploit the interactions between biomaterials and immune tissues to enable more specific control of immune function. One approach involves direct delivery of synthetic vaccine carriers to lymph nodes (LNs), key tissues that coordinate immune response. We have combined direct LN injection with biomaterials to establish a platform to study the link between local LN function and systemic immunity by probing the roles of signal density and material properties. We are also exploiting this direct delivery for therapeutic vaccination to combat autoimmunity. In mouse models of multiple sclerosis, a single injection at the peak of disease shifts the LN microenvironment towards tolerance, permanently reversing paralysis without compromising normal immune function. The second focus area is the design of new modular materials we have created using polyionic immune signals to form stable capsules self-assembled entirely from immune signals. These immune polyelectrolyte multilayers (iPEMs) co-localize signals to draining LNs after injection, and allow selective activation or deactivation of inflammatory pathways (e.g., toll-like receptors) without carrier components such as polymers. iPEMs built from antigen and toll-like receptor (TLR) agonists enhance dendritic cell function, expand antigen-specific T cells, and provide protection during mouse tumor challenge. In contrast, iPEMs assembled from antigen and suppressive TLR ligands promote tolerance in mouse cells, mouse models of MS, and samples from human MS patients. 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.

Harnessing biomaterials to study and engineer lymph node function

253rd National Meeting (2017)

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