Biodegradable Particles as Vaccine Delivery Systems: Size Matters
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Poly(lactide-co-glycolide) (PLGA) particles have strong potential as antigen delivery systems. The size of PLGA particles used to vaccinate mice can affect the magnitude of the antigen-specific immune response stimulated. In this study, we fabricated and characterized 17 μm, 7 μm, 1 μm, and 300 nm PLGA particles coloaded with a model antigen ovalbumin (OVA) and CpG oligodeoxynucleotides (CpG ODN). PLGA particles demonstrated a size-dependent burst release followed by a more sustained release of encapsulated molecules. PLGA particles that were 300 nm in size showed the highest internalization by, and maximum activation of, dendritic cells. The systemic antigen-specific immune response to vaccination was measured after administration of two intraperitoneal injections, 7 days apart, of 100 μg OVA and 50 μg CpG ODN in C57BL/6 mice. In vivo studies showed that 300 nm sized PLGA particles generated the highest antigen-specific cytotoxic T cell responses by days 14 and 21. These mice also showed the highest IgG2a:IgG1 ratio of OVA-specific antibodies on day 28. This study suggests that the smaller the PLGA particle used to deliver antigen and adjuvants the stronger the antigen-specific cytotoxic T cell response generated.
KEY WORDSCpG ODN cytotoxic T lymphocytes dendritic cells nanoparticles poly (lactide-co-glycolide) vaccine
We gratefully acknowledge support from the American Cancer Society (RSG-09-015-01-CDD) and the National Cancer Institute at the National Institutes of Health (1R21CA128414-01A2/UI Mayo Clinic Lymphoma SPORE). We acknowledge Y. Krishnamachari, Senior Scientist, Merck, Inc. for contributing her expertise to the manuscript. We thank the staff of the Central Microscopy Research Facility, University of Iowa for their assistance with microscopy.
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