Dissertation Defense Announcement
To:  The George Mason University Community

Candidate: Allison Teunis

Program: PhD in Biosciences



Date:   Friday April 14, 2017

Time:   2:00 PM
Place:  George Mason University
             Science & Tech campus

             IABR, Room 1004



Title: "Development of Chemokine-Releasing Microparticles for the Manipulation of Immune Cell Responses"
Committee Chair: Dr. Serguei Popov
Committee Members:  Dr. Lance Liotta, Dr. Monique van Hoek,  Dr. Virginia Espina

A copy of the dissertation will be available in the Johnson Center Gateway Library. All are invited to attend the defense.
ABSTRACT:
A confounding obstacle faced by the medical field is the ability of many disease agents to suppress the body's immune system, allowing them to avoid elimination by the host. In this study, we have proposed a novel nanotechnology-based platform for achieving sustained delivery of immune-modulating chemokines (CKs) as a means for overcoming immunosuppression. Functionalized hydrogel microparticles (MPs) were coupled with a variety of affinity baits and measured for their abilities to bind and release CKs. Favorable chemokine-loaded MP (CK-MP) pairs demonstrated affinities in the range of low micromolar to high nanomolar and maintained sustained CK release for more than 20 h in vivo. Upon injection in an established mouse model of subcutaneous hind footpad (FP) injection, a significant portion of the MPs accumulated in the regional draining lymph nodes (LNs). MP diffusion through the lymphatics and delivery by phagocytic cells to the LNs was advantageous as Bacillus anthracis spores, our model inducer of immunosuppression, injected in this manner demonstrate the same distribution and localization in the host. Pre-treatment of spore-challenged animals with MPs loaded with neutrophil-attracting CKs (CK-MPs) provided significant protection against the infectious bacterium, even in the absence of any additional antibiotic intervention, although therapeutic (post-treatment) injection of the CK-MPs was not protective by itself. It was found that both the bait-coupled MPs and their released CKs played important roles contributing to improved survival. The MPs possessed intrinsic adjuvant behavior, inducing endogenous expression of several pro-inflammatory cytokines and CKs to promote further stimulation of immune activity favorable for the host. Further mechanistic evidence for the protection conferred in vivo was that epidermal resident antigen-presenting cells (Langerhans cells) were found activated and migrated to the local LN in response to CK-MP treatment. We propose further investigation into the potential clinical use of CK-MPs for achieving predictable, sustained modulation of immune activity.
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