Calcium phosphate nanoparticles show an effective activation of the innate immune response in vitro and in vivo after functionalization with flagellin
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For subunit vaccines, adjuvants play a key role in shaping the magnitude, persistence and form of targeted antigen-specific immune response. Flagellin is a potent immune activator by bridging innate inflammatory responses and adaptive immunity and an adjuvant candidate for clinical application. Calcium phosphate nanoparticles are efficient carriers for different biomolecules like DNA, RNA, peptides and proteins. Flagellin-functionalized calcium phosphate nanoparticles were prepared and their immunostimulatory effect on the innate immune system, i.e. the cytokine production, was studied. They induced the production of the proinflammatory cytokines IL-8 (Caco-2 cells) and IL-1β (bone marrow-derived macrophages; BMDM) in vitro and IL-6 in vivo after intraperitoneal injection in mice. The immunostimulation was more pronounced than with free flagellin.
Keywordscalcium phosphate nanoparticle immunostimulation innate immune system flagellin adjuvants
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- Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P, Suzuki S, Shaw M H, Kim Y G, and Núñez G. 2012. NLRC4-driven interleukin-1β production discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat. Immunol., 13: 449–456.PubMedCentralPubMedCrossRefGoogle Scholar
- Knuschke T, Sokolova V, Rotan O, Wadwa M, Tenbusch M, Hansen W, Staeheli P, Epple M, Buer J, and Westendorf A M. 2013. Immunization with biodegradable nanoparticles efficiently induces cellular immunity and protects against influenza virus infection. J. Immunol., 190: 6221–6229.PubMedCrossRefGoogle Scholar
- Sokolova V, Knuschke T, Kovtun A, Buer J, Epple M, and Westendorf A M. 2010. The use of calcium phosphate nanoparticles encapsulating toll-like receptor ligands and the antigen hemagglutinin to induce dendritic cell maturation and T cell activation. Biomaterials, 31: 5627–5633.PubMedCrossRefGoogle Scholar
- Yang J, Zhong M, Zhang Y, Zhang E, Sun Y, Cao Y, Li Y, Zhou D, He B, Chen Y, Yang Y, Yu J, and Yan H. 2013. Antigen replacement of domains D2 and D3 in flagellin promotes mucosal IgA production and attenuates flagellin-induced inflammatory response after intranasal immunization. Hum. Vaccin. Immunother., 9: 1084–1092.PubMedCrossRefGoogle Scholar
- Yang J, Zhang E, Liu F, Zhang Y, Zhong M, Li Y, Zhou D, Chen Y, Cao Y, Xiao Y, He B, Yang Y, Sun Y, Lu M, and Yan H. 2013. Flagellins of Salmonella Typhi and non-pathogenic Escherichia coli are differentially recognized through NLRC4 pathway in macrophages. J. Innate Immunity: (in press).Google Scholar