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Gold Nanoparticles as a Vaccine Platform: Influence of Size and Shape on Immunological Responses in Vitro and in Vivo

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Research Institute for Electronic Science (RIES), Hokkaido University, N21W10, Sapporo 001-0021, Japan
Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-8628, Japan
§ Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan
Global COE Program, Hokkaido University, Sapporo 060-0818, Japan
Division of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan
# Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
*Address correspondence to [email protected]
Cite this: ACS Nano 2013, 7, 5, 3926–3938
Publication Date (Web):April 30, 2013
Copyright © 2013 American Chemical Society

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    This paper demonstrates how the shape and size of gold nanoparticles (AuNPs) affect immunological responses in vivo and in vitro for the production of antibodies for West Nile virus (WNV). We prepared spherical (20 and 40 nm in diameter), rod (40 × 10 nm), and cubic (40 × 40 × 40 nm) AuNPs as adjuvants and coated them with WNV envelope (E) protein. We measured anti-WNVE antibodies after inoculation of these WNVE-coated AuNPs (AuNP-Es) into mice. The 40 nm spherical AuNP-Es (Sphere40-Es) induced the highest level of WNVE-specific antibodies, while rod AuNP-Es (Rod-Es) induced only 50% of that of Sphere40-E. To examine the mechanisms of the shape-dependent WNVE antibody production, we next measured the efficiency of cellular uptake of AuNP-Es into RAW264.7 macrophage cells and bone-marrow-derived dendritic cells (BMDCs) and the subsequent cytokine secretion from BMDCs. The uptake of Rod-Es into the cells proceeded more efficiently than those of Sphere-Es or cubic WNVE-coated AuNPs (Cube-Es), suggesting that antibody production was not dependent on the uptake efficiency of the different AuNP-Es. Cytokine production from BMDCs treated with the AuNP-Es revealed that only Rod-E-treated cells produced significant levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18), indicating that Rod-Es activated inflammasome-dependent cytokine secretion. Meanwhile, Sphere40-Es and Cube-Es both significantly induced inflammatory cytokine production, including tumor necrosis factor-α (TNF-α), IL-6, IL-12, and granulocyte macrophage colony-stimulating factor (GM-CSF). These results suggested that AuNPs are effective vaccine adjuvants and enhance the immune response via different cytokine pathways depending on their sizes and shapes.

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