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Gold Nanoparticles Coimmobilized with Small Molecule Toll-Like Receptor 7 Ligand and α‑Mannose as Adjuvants
journal contribution
posted on 2019-10-09, 19:44 authored by Hiroyuki Shinchi, Toru Yamaguchi, Toshiro Moroishi, Masaharu Yuki, Masahiro Wakao, Howard B. Cottam, Tomoko Hayashi, Dennis A. Carson, Yasuo SudaAdjuvants enhance
the immune response during vaccination. Among
FDA-approved adjuvants, aluminum salts are most commonly used in vaccines.
Although aluminum salts enhance humoral immunity, they show a limited
effect for cell-mediated immune responses. Thus, further development
of adjuvants that induce T-cell-mediated immune response is needed.
Toll-like receptors (TLRs) recognizing specific pathogen-associated
molecular patterns activate innate immunity, which is crucial to shape
adaptive immunity. Using TLR ligands as novel adjuvants in vaccines
has therefore attracted substantial attention. Among them a small
molecule TLR7 ligand, imiquimod, has been approved for clinical use,
but its use is restricted to local administration due to unwanted
adverse side effects when used systematically. Since TLR7 is mainly
located in the endosomal compartment of immune cells, efficient transport
of the ligand into the cells is important for improving the potency
of the TLR7 ligand. In this study we examined gold nanoparticles (GNPs)
immobilized with α-mannose as carriers for a TLR7 ligand to
target immune cells. The small molecule synthetic TLR7 ligand, 2-methoxyethoxy-8-oxo-9-(4-carboxy
benzyl)adenine (1V209), and α-mannose were coimmobilized via
linker molecules consisting of thioctic acid on the GNP surface (1V209-αMan-GNPs).
The in vitro cytokine production activity of 1V209-αMan-GNPs
was higher than that of the unconjugated 1V209 derivative in mouse
bone marrow-derived dendritic cells and in human peripheral blood
mononuclear cells. In the in vivo immunization study, 1V209-αMan-GNPs
induced significantly higher titers of IgG2c antibody specific to
ovalbumin as an antigen than did unconjugated 1V209, and splenomegaly
and weight loss were not observed. These results indicate that 1V209-αMan-GNPs
could be useful as safe and effective adjuvants for development of
vaccines against infectious diseases and cancer.
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cytokine production activityα- mannoseunconjugated 1 V 209vivo immunization study1 V 209-αManshape adaptive immunitymouse bone marrow-derived dendritic cellsvaccinegold Nanoparticles Coimmobilizedaluminum saltsTLR 7 ligandGNPIgG 2c antibodymolecule TLR 7 ligandadjuvantresponseSmall Molecule Toll-Like Receptor 7 Ligand
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