Autoimmune diabetes (type 1 diabetes; T1D) is a disease of failed immune regulation. A vaccine for T1D aims to use antigenic material to stimulate regulatory immune responses and restore immune homeostasis. Challenges for successful implementation include finding the best mode of delivery and the best adjuvant for the vaccine to be effective. We have assembled a team of experts in biomaterials and T1D to address these challenges. The goal of this work is to investigate the delivery of relevant vaccine components incorporated into a controlled release biomaterial delivery system for a T1D vaccine. The ability to target and deliver immunomodulating factors in a controlled way to critical immune cell types is key. Our strategy involves the injectable administration of factors (e.g., antigen and adjuvant) formulated in an injectable, in-situ forming hydrogel co-mixed with adjuvant and biodegradable microparticles encapsulating insulin antigen. The adjuvant strategy taken here is along the lines of recent clinical trials for T1D (showing safety but not efficacy), administering pro-inflammatory adjuvants plus antigen with the expectation that inflammation can be resolved with subsequent tolerance to pancreatic antigen. This biomaterial delivery system serves as a temporary microenvironment to attract and educate immune cells. We hypothesize this biomaterial-based vaccine system will recruit and educate immune cells to become tolerant of insulin, ameliorating T1D. The proposed research is innovative, representing targeted, controlled delivery of vaccine components aiming to restore tolerance to T1D self-antigens. Our in vivo preliminary data demonstrate that our approach is promising for the amelioration of T1D.

Public Health Relevance

Type-1 diabetes is an autoimmune disease with enormous personal and economic impact in the US. Therapeutic vaccination approaches for type-1 diabetes hold promise to correct these autoimmune responses. The objective of this application is to engineer a biomaterials-based system with controlled release and targeting properties, as an injectable vaccine to retrain the immune system to toward diabetes relevant self-antigen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK098589-02
Application #
8877504
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Pawlyk, Aaron C
Project Start
2014-07-01
Project End
2018-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Florida
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Farhadi, Shaheen A; Bracho-Sanchez, Evelyn; Fettis, Margaret M et al. (2018) Locally anchoring enzymes to tissues via extracellular glycan recognition. Nat Commun 9:4943
Farhadi, Shaheen A; Bracho-Sanchez, Evelyn; Freeman, Sabrina L et al. (2018) Enzymes as Immunotherapeutics. Bioconjug Chem 29:649-656
Fernando, Lawrence P; Lewis, Jamal S; Evans, Brian C et al. (2018) Formulation and characterization of poly(propylacrylic acid)/poly(lactic-co-glycolic acid) blend microparticles for pH-dependent membrane disruption and cytosolic delivery. J Biomed Mater Res A 106:1022-1033
Zaveri, Toral D; Dolgova, Natalia V; Lewis, Jamal S et al. (2017) Macrophage integrins modulate response to ultra-high molecular weight polyethylene particles and direct particle-induced osteolysis. Biomaterials 115:128-140
Stewart, Joshua M; Keselowsky, Benjamin G (2017) Combinatorial drug delivery approaches for immunomodulation. Adv Drug Deliv Rev 114:161-174
Keselowsky, Benjamin G; Lewis, Jamal S (2017) Dendritic cells in the host response to implanted materials. Semin Immunol 29:33-40
Cho, Jonathan J; Stewart, Joshua M; Drashansky, Theodore T et al. (2017) An antigen-specific semi-therapeutic treatment with local delivery of tolerogenic factors through a dual-sized microparticle system blocks experimental autoimmune encephalomyelitis. Biomaterials 143:79-92
Yang, Lirong; Bracho-Sanchez, Evelyn; Fernando, Lawrence P et al. (2017) Poly(2-propylacrylic acid)/poly(lactic-co-glycolic acid) blend microparticles as a targeted antigen delivery system to direct either CD4+ or CD8+ T cell activation. Bioeng Transl Med 2:202-211
Bracho-Sanchez, E; Xia, C Q; Clare-Salzler, M J et al. (2016) Micro and Nano Material Carriers for Immunomodulation. Am J Transplant 16:3362-3370
Acharya, Abhinav P; Carstens, Matthew R; Lewis, Jamal S et al. (2016) A cell-based microarray to investigate combinatorial effects of microparticle-encapsulated adjuvants on dendritic cell activation. J Mater Chem B 4:1672-1685

Showing the most recent 10 out of 13 publications