Event
BIOE Seminar: Lipid Nanoparticle Templated Anti-opioid Vaccine
Friday, August 19, 2022
9:00 a.m.-10:00 a.m.
A. James Clark Hall, Room #2132
Dr. Chris Jewell
cmjewell@umd.edu
Bruno de Geest
Professor
Ghent University (Belgium)
Please note, there is no virtual component to this event. Attendance will be in person only.
A lipid nanoparticle templated anti-opioid vaccine
The abusive use of opioid prescription drugs, often referred to as "the opioid crisis," has become a major global problem facing an exuberant number of deaths. To tackle this tremendous challenges, anti-opioid immunotherapy is considered as a promising therapy. The current generation of anti-opioid vaccines are based on random covalent conjugation of opioid haptens to a carrier protein in combination with an admixed adjuvant, and most likely do not fully embrace the potential of anti-opioid immunotherapy due to immunodominance of the carrier protein, sub-optimal priming of the immune system and translational challenges due to difficulties to reproduce and characterize hapten-protein conjugates. Focusing on fentanyl as a prominent opioid of concern, we present a more rational anti-opioid vaccine design based on a non-covalent assembly of opioid haptens, T-helper epitope and an immune-stimulant into a single lipid nanoparticle (LNP). The latter is engineered for optimal delivery to secondary lymphoid organs and to mediate multivalent hapten ligand exposure on a spherical nanoparticle template for optimal induction of hapten-specific antibody responses. We use peptide as a format for the T helper epitope antigen, and for this purpose we developed a generic strategy to load peptide antigens into LNP through electrostatic interaction with an ionizable lipid. As a molecular adjuvant we evaluated several TLR agonists and loaded these into LNP through either hydrophobic or electrostatic interaction. Furthermore we demonstrate how LNP design affects the amplitude and quality of the anti-opioid immune response and whether this confers protection in pre-clinical models of opioid overdosing.
About the Speaker:
Prof. de Geest graduated as a chemical engineer in 2003 from Ghent University where he obtained his Ph.D. in pharmaceutical sciences in 2006 on self-assembly of polyelectrolyte multilayer capsules. For this work he was awarded the graduate student award for pharmaceutical technology from the AAPS and the Andreas Deleenheer award from Ghent University. After 2 years of postdoctoral research at Utrecht University (The Netherlands) Bruno returned to the Ghent University. In October 2012 he was appointed as Assistant Professor, in 2017 as Associate Professor, and in February 2019 as Full Professor at the Department of Pharmaceutics at Ghent University. He is currently a recipient of an ERC Consolidator Grant. His lab leverages the power of chemistry, biotechnology and nanotechnology to engineer the immune system at better responding to internal threats such as cancer and external threats such as viral pathogens and lethal drug substances. In this context the group aims to intervene at different levels in the process of innate immune activation, antigen presentation and the generation of adaptive immunity to clear or protect the host from a specific threat.
