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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Enhanced immunogenicity of a tricomponent mannan tetanus toxoid conjugate vaccine targeted to dendritic cells via Dectin-1 by incorporating β-glucan
Journal of Immunology, Volume 190, No. 8, Year 2013
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Description
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. The Journal of Immunology, 2013, 190: 4116-4128. Copyright © 2013 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Lipiński, Tomasz
Canada, Edmonton
Alberta Glycomics Centre
Poland, Wroclaw
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences
Fitieh, Amira Mohammed
Canada, Edmonton
University of Alberta
Egypt, Giza
Faculty of Science
St-Pierre, Joëlle
Canada, Edmonton
University of Alberta
Ostergaard, Hanne L.
Canada, Edmonton
University of Alberta
Bundle, David R.
Canada, Edmonton
Alberta Glycomics Centre
Touret, Nicolas
Canada, Edmonton
University of Alberta
Statistics
Citations: 65
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.4049/jimmunol.1202937
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Maternal And Child Health