2010 - Transplantomics and Biomarkers in Transplantation



Presenter: Kathleen, Kelly, Los Angeles, USA
Authors: Kathleen Kelly

Kathleen Kelly, Associate Professor and Technical Director, Department of Pathology & Laboratory Medicine, David Geffen School of Medicine at UCLA, UCLA, Los Angeles, CA, USA
Learning Objectives:
1. Discuss the application of Nanotechnology in clinical practice and research.
2. Recognize the contribution of dendritic cells for inducing immunity.
3. Understand the role of an inflammasome in immunity.
Mucosal immune responses provide superior protection against disease but the ability of the immune system to protect mucosal surfaces against invasion by pathogens is a poorly understood process. Currently there are no FDA-approved adjuvants capable of stimulating robust mucosal immunity.  Protective immunity requires activation of the innate immune system and adjuvants provide this critical stimulation. However, the mechanism whereby adjuvants activate innate immunity was not known until recently. Adjuvants initiate adaptive immune responses by activating a class of innate pathogen receptors called pattern recognition receptors (PRRs), specifically Toll-like receptors and Inflammasomes. Nanoparticles have the unique ability to deliver immunogenic peptides and activate PRRs. This has accelerated vaccine design by engineering nanoparticle to selectively activate protective immunity. To test the utility of vaults as mucosal vaccine delivery platforms, we chose an infection that relies on cell-mediated mucosal immune responses for elimination and is a significant burden on health care; Chlamydia trachomatis infection. C. trachomatis is a prominent cause of STI, with approximately 92 million cases occurring annually and is an instigator of female reproductive dysfunction. T helper immune cells (Th1) must be present within vaginal tissues in order to eradicate infection.  We encapsulated an immunogenic protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for enhanced immunity. Our data indicate that vaults engineered to deliver antigens may in fact act as “smart adjuvants” directing Th1 mediated immunity in mucosal tissues without inducing excessive inflammation.  Thus, natural nanoparticles called vaults can be engineered to act as “smart” adjuvants and serve as platforms to induce mucosal immunity against mucosal infections.

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