Enhanced immunogenicity of a tricomponent mannan tetanus toxoid conjugate vaccine targeted to dendritic cells via Dectin-1 by incorporating β-glucan.
نویسندگان
چکیده
In a previous attempt to generate a protective vaccine against Candida albicans, a β-mannan tetanus toxoid conjugate showed poor immunogenicity in mice. To improve the specific activation toward the fungal pathogen, we aimed to target Dectin-1, a pattern-recognition receptor expressed on monocytes, macrophages, and dendritic cells. Laminarin, a β-glucan ligand of Dectin-1, was incorporated into the original β-mannan tetanus toxoid conjugate providing a tricomponent conjugate vaccine. A macrophage cell line expressing Dectin-1 was employed to show binding and activation of Dectin-1 signal transduction pathway by the β-glucan-containing vaccine. Ligand binding to Dectin-1 resulted in the following: 1) activation of Src family kinases and Syk revealed by their recruitment and phosphorylation in the vicinity of bound conjugate and 2) translocation of NF-κB to the nucleus. Treatment of immature bone marrow-derived dendritic cells (BMDCs) with tricomponent or control vaccine confirmed that the β-glucan-containing vaccine exerted its enhanced activity by virtue of dendritic cell targeting and uptake. Immature primary cells stimulated by the tricomponent vaccine, but not the β-mannan tetanus toxoid vaccine, showed activation of BMDCs. Moreover, treated BMDCs secreted increased levels of several cytokines, including TGF-β and IL-6, which are known activators of Th17 cells. Immunization of mice with the novel type of vaccine resulted in improved immune response manifested by high titers of Ab recognizing C. albicans β-mannan Ag. Vaccine containing laminarin also affected distribution of IgG subclasses, showing that vaccine targeting to Dectin-1 receptor can benefit from augmentation and immunomodulation of the immune response.
منابع مشابه
Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating b-Glucan
متن کامل
Production and Investigation of the Effects of Polysaccharide-Protein Conjugate Vaccine in Prevention of Salmonella Typhimurium Infections in Mouse Model
S.typhimurium is a gram negative bacterium causing serious enteric or extraintestinal infections in human, cattle and birds. These kinds of infections may lead to some permanent or nonpermanent complications like endophthalmitis, Guillain-Barre syndrome and osteomyelitis . Multi-resistant strains of S.typhimurium have been reported from several countries, and these infections are a major public...
متن کاملParticulate β-glucans synergistically activate TLR4 and Dectin-1 in human dendritic cells.
SCOPE The major receptor for β(1-3)-glucans on immune cells is considered to be Dectin-1 receptor. Particulate β-glucans induce stronger immune responses than soluble β-glucans by clustering of Dectin-1 receptors. Here, it was hypothesized that activation of other pattern recognition receptors such as Toll-like receptor 4 (TLR4) can also contribute to enhanced activity of immune cells after exp...
متن کاملImproved Immunogenicity of Tetanus Toxoid by Brucella abortus S19 LPS Adjuvant
Background: Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram nega...
متن کاملSelf-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis
Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2-mannotriose [β-(Man)(3)] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic gly...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 190 8 شماره
صفحات -
تاریخ انتشار 2013