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The impact of nanoparticle ligand density on dendritic-cell targeted vaccines
Open accessAbstract
Dendritic-cell (DC) targeted antigen delivery systems hold promise for enhancing vaccine efficacy and delivery of therapeutics. However, it is not known how the number and density of targeting ligands on such systems may affect DC function and subsequent T cell response. We modified the surface of biodegradable nanoparticles loaded with antigen with different densities of the mAb to the DC lectin DEC-205 receptor and assessed changes in the cytokine response of DCs and T cells. DEC-205 targeted nanoparticles unexpectedly induced a differential cytokine response that depended on the density of ligands on the surface. Strikingly, nanoparticle surface density of DEC-205 mAb increased the amount of anti-inflammatory, IL-10, produced by DCs and T cells. Boosting mice with DEC-205 targeted OVA-nanoparticles after immunization with an antigen in CFA induced a similar pattern of IL-10 response. The correlation between DC production of IL-10 as a function of the density of anti-DEC-205 is shown to be due to cross-linking of the DEC-205 receptor. Cross-linking also increased DC expression of the scavenger receptor CD36, and blockade of CD36 largely abrogated the IL-10 response. Our studies highlight the importance of target ligand density in the design of vaccine delivery systems.
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NPs surface modification with an antibody against the DC lectin DEC-205 receptor induced IL-10 production by DCs and T cells in vitro; intraperitoneal injection into OVA-primed mice produced a similar IL-10 pattern dependent on the density of surface modification.
“Recently, NPs’ surface modification with an antibody against the DC lectin DEC-205 receptor induced the production of IL-10 by DCs and T cells in vitro. When these modified particles were intraperitoneally injected into ovalbumin (OVA) primed mice, a similar IL-10 pattern was observed, which was dependent on the density of surface modification [69].”
From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [69]
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Metadata
- Authors
- Bandyopadhyay, A., Fine, R. L., Demento, S., Bockenstedt, L. K., & Fahmy, T. M.
- Affiliations
- Yale University (US)
- Williams College (US)
- Corresponding author
- Fahmy, Tarek M.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 32
- Issue
- 11
- Pages
- 3094-3105
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC4570971
- OpenAlex
- W2086073469
- Cited by
- 141
- References
- 56
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 9 · 2021: 14 · 2020: 11 · 2019: 11 · 2018: 9 · 2017: 10 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 12 · 2012: 20
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NSF NIRT (CTS-0609326)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- antibody cross-linking, IL-10, CD36 scavenger receptor, antigen delivery, biodegradable nanoparticles, T cell response, cytokine response, ovalbumin
- MeSH terms
- Animals, Dendritic Cells, Flow Cytometry, Mice, Inbred C57BL, Receptors, Cell Surface, T-Lymphocytes, Vaccines, Antigens, CD, Minor Histocompatibility Antigens, Cytokines, Interleukin-10, Microscopy, Confocal, Lectins, C-Type, Mice, Nanoparticles
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