We are pleased to welcome Professor Kim Woodrow of the University of Washington as our 2016-2017 Rising Star speaker.
Please join us!
Wednesday, September 21
12:00 – 1:00 PM
106 Stanley Hall
“Engineering the mucosal microenvironment promotes targeting of particulate and cellular immunotherapies to lymphoid organs”
Compartmentalization within the mucosal immune system leads to mucosal immune responses that are strongest at and proximal to the site of mucosal immunization. Within the female reproductive tract (FRT) immunogens must be transported distally to draining lymph nodes (dLNs) since there are no local organized lymphoid structures equivalent to those found at other mucosal sites. However, a surfeit of mucosal barriers must be safely and effectively navigated to cross the epithelium and gain access to migratory cells and lymphatic drainage that provide entry into dLNs. Here, we describe inherent barriers in the FRT for transporting particulate vaccines and activating mucosal DCs. We quantify that only a low fraction of about 1 in 4 nodes (25%) accumulates 20 nm- or 200 nm-sized NP that are dosed vaginally. In this case, we also observe limited NP-cell interactions locally in the vaginal tissue or distally in dLNs. Furthermore, we find under homeostatic conditions that tissue-derived mucosal DCs from the FRT and dLNs exhibit a low capacity for antigen presentation and fail to prime T cell proliferation. To overcome these innate barriers, we employ a naturally occurring polysaccharide to safely enhance permeability of the epithelium and promote trafficking of NPs and immunogenic DCs to dLNs after vaginal dosing. This adjuvanting polysaccharide enhances NP-cell interactions resulting in a doubling of the number of positive dLNs and specifically improves transport of larger 200 nm NP to the IGLN from a frequency of ~10% to ~75%. Immunogenic DCs that are programmed exogenously and adoptively transferred topically to the vaginal mucosa are also transported to the dLNs and prime both CD4+ and CD8+ T cell proliferation. By employing strategies that safely overcome barriers presented by the mucosal microenvironment, we can target particulate and cellular immunotherapies to lymphoid organs. Our approach may be useful for modulating mucosal immunity and understanding the quality, quantity and plasticity of mucosal DCs for vaccine design.
Kim A. Woodrow is an Associate Professor in the Department of Bioengineering at the University of Washington. She earned her MS and PhD degrees from Stanford in Chemical Engineering. From 2006-2009, Dr. Woodrow was a postdoctoral fellow in Biomedical Engineering at Yale University. Since joining UW Bioengineering in 2010, Dr. Woodrow’s research interests have focused on applications at the intersection of engineering and mucosal biology, where her lab works on the design and synthesis of biomaterials for applications in mucosal infections and mucosal immunity. Dr. Woodrow is an NIH-funded investigator, the recipient of the Creative and Novel Ideas in HIV Research (CNIHR) award from the Office of AIDS Research, a recipient of grants from The Bill and Melinda Gates Foundation, and was awarded a 2012 NIH Director’s New Innovator Award. She has served on the technical program committee for BMES and the international HIV R4P conference. In 2015, she was recognized with the University of Washington Undergraduate Research Mentor Award and as the Science in Medicine New Investigator for the School of Medicine.