Search results for "CpG Oligodeoxynucleotide"
showing 6 items of 6 documents
Protein corona–mediated targeting of nanocarriers to B cells allows redirection of allergic immune responses
2018
Background Nanoparticle (NP)–based vaccines are attractive immunotherapy tools because of their capability to codeliver antigen and adjuvant to antigen-presenting cells. Their cellular distribution and serum protein interaction ("protein corona") after systemic administration and their effect on the functional properties of NPs is poorly understood. Objectives We analyzed the relevance of the protein corona on cell type–selective uptake of dextran-coated NPs and determined the outcome of vaccination with NPs that codeliver antigen and adjuvant in disease models of allergy. Methods The role of protein corona constituents for cellular binding/uptake of dextran-coated ferrous nanoparticles (DE…
Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases
2013
Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious tha…
Heat shock protein-antigen fusions lose their enhanced immunostimulatory capacity after endotoxin depletion.
2008
Heat shock proteins (HSPs) induce cross-presentation of antigens by dendritic cells (DC) as well as DC maturation. These properties make HSP antigen complexes good candidates to prime CD8 T cell responses against tumor-associated antigens. In this study, we analyzed four different members of the HSP70 family fused to a fragment of ovalbumin (OVA) as a model tumor antigen. E. coli-derived recombinant HSP70-OVA fusion proteins efficiently primed antigen-specific cytotoxic T cells in short-term in vivo immunization assays. Because of concerns that the adjuvant effect of HSPs may be due to endotoxin contamination, we studied this issue in detail. Induction of OVA-specific cytotoxicity was signi…
Precision wormlike nanoadjuvant governs potency of vaccination
2021
It remains unclear how the precise length of one-dimensional nanovehicles influences the characters of vaccination. Here, a unimolecular nanovehicle with tailored size and aspect ratio (AR) is applied to deliver CpG oligodeoxynucleotide, a Toll-like receptor (TLR) 9 agonist, as an adjuvant of recombinant hepatitis B virus surface antigen (rHBsAg), for treating chronic hepatitis B (CHB). Cationic nanovehicles with fixed width (ca. 45 nm) but varied length (46 nm-180 nm), AR from 1 to 4, are prepared through controlled polymerization and are loaded with CpG by electrostatic interaction. We reveal that the nanoadjuvant with AR = 2 shows the highest retention in proximal lymph nodes. Importantl…
Excessive CpG 1668 stimulation triggers IL-10 production by cDC that inhibits IFN-alpha responses by pDC.
2008
Upon stimulation with a wide range of concentrations of CpG oligodeoxynucleotide 2216 (CpG 2216), plasmacytoid DC are induced to produce type I IFN (IFN-alpha/beta). In contrast, CpG 1668 shows a bell-shaped dose-response correlation, i.e. only intermediate but not high doses of CpG 1668 induce IFN-alpha/beta. Interestingly, high-dose CpG 1668 completely inhibited IFN-alpha responses induced by CpG 2216. Experiments using supernatant of high-dose CpG-1668-treated cells indicated that secreted inhibitor(s) mediated the IFN-alpha shut-off. Among modulating cytokines, IL-10 turned out to be one important negative regulator. In line with this, supernatants of IL-10-deficient DC cultures stimula…
Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment.
2015
The immunostimulatory ability of synthetic oligonucleotides containing CpG motifs (CpG-ODN), agonists of Toll-like receptor 9 (TLR9), can be harnessed to promote antitumor immunity by their application at the tumor site to stimulate local activation of innate immunity; however, particularly in the lung, tumor-associated immunosuppression can subvert such antitumor innate immune responses. To locally maintain continuous activation of innate subpopulations while inhibiting immunosuppressive cells, we evaluated aerosol delivery CpG-ODN combined with Poly(I:C), a TLR3 agonist able to convert tumor-supporting macrophages to tumoricidal effectors, in the treatment of B16 melanoma lung metastases …