title: Clearance of depot vaccine SPIO-labeled antigen and substrate visualized using MRI.
abstract: Immunotherapies, including peptide-based vaccines, are a growing area of cancer research, and understanding their mechanism of action is crucial for their continued development and clinical application. Exploring the biodistribution of vaccine components may be key to understanding this action. This work used magnetic resonance imaging (MRI) to characterize the in vivo biodistribution of the antigen and oil substrate of the vaccine delivery system known as DepoVax(TM). DepoVax uses a novel adjuvanted lipid-in-oil based formulation to solubilise antigens and promote a depot effect. In this study, antigen or oil were tagged with superparamagnetic iron oxide (SPIO), making them visible on MR images. This enables tracking of individual vaccine components to determine changes in biodistribution. Mice were injected with SPIO-labeled antigen or SPIO-labeled oil, and imaged to examine clearance of labeled components from the vaccine site. The SPIO-antigen was steadily cleared, with nearly half cleared within two months post-vaccination. In contrast, the SPIO-oil remained relatively unchanged. The biodistribution of the SPIO-antigen component within the vaccine site was heterogeneous, indicating the presence of active clearance mechanisms, rather than passive diffusion or drainage. Mice injected with SPIO-antigen also showed MRI contrast for several weeks post-vaccination in the draining inguinal lymph node. These results indicate that MRI can visualize the in vivo longitudinal biodistribution of vaccine components. The sustained clearance is consistent with antigen up-take and trafficking by immune cells, leading to accumulation in the draining lymph node, which corresponds to the sustained immune responses and reduced tumor burden observed in vaccinated mice.
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada; School of Biomedical Engineering, Dalhousie University, Halifax, NS, Canada.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Brewer
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
authors.forename: Kerry
authors.initials: K
authors.lastname: Lake
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pelot
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada; Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Marianne M
authors.initials: MM
authors.lastname: Stanford
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
authors.forename: Drew R
authors.initials: DR
authors.lastname: DeBay
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Penwell
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada; Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Weir
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada; Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Mohan
authors.initials: M
authors.lastname: Karkada
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Mansour
authors.affiliation: School of Biomedical Engineering, Dalhousie University, Halifax, NS, Canada; Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada; Departments of Radiology and Physics, Dalhousie University, Halifax, NS, Canada. Electronic address: Chris.Bowen@dal.ca.
authors.forename: Chris V
authors.initials: CV
authors.lastname: Bowen
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005290:Ferric Compounds / Q000032:analysis; D006801:Humans; D008279:Magnetic Resonance Imaging; D008810:Mice, Inbred C57BL; D014612:Vaccines / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D003692:Delayed-Action Preparations; D005290:Ferric Compounds; D014612:Vaccines; C000499:ferric oxide
keywords: Cancer; HPV-16; MRI; Superparamagnetic iron oxide (SPIO); Vaccines