Serving the Society Since 1986
Advanced Search
Volume 29 Issue 1
February 2014
    Citation: Diana Kozlova, Viktoriya Sokolova, Maohua Zhong, Ejuan Zhang, Jingyi Yang, Wei Li, Yi Yang, Jan Buer, Astrid Maria Westendorf, Matthias Epple, Huimin Yan. Calcium phosphate nanoparticles show an effective activation of the innate immune response in vitro and in vivo after functionalization with flagellin .VIROLOGICA SINICA, 2014, 29(1) : 33-39.  http://dx.doi.org/10.1007/s12250-014-3379-0
    shu

    Calcium phosphate nanoparticles show an effective activation of the innate immune response in vitro and in vivo after functionalization with flagellin

    • 1.

      Institute of Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Du isburg-Essen, Essen 45117, Germany

    • 2.

      Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

    • 3.

      Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany

    • Corresponding author: Matthias Epple, matthias.epple@uni-due.de
      Huimin Yan, hmyan@wh.iov.cn
    • Received Date: 17 September 2013
      Accepted Date: 19 November 2013
      Published Date: 26 December 2013
      Available online: 01 February 2014
    • 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.
    • 加载中

      1. Amicizia D, Domnich A, Panatto D, Lai P L, Cristina M L, Avio U, and Gasparini R. 2013. Epidemiology of tick-borne encephalitis (TBE) in Europe and its prevention by available vaccines. Hum Vaccin Immunother, 9: 1163-1171.
          doi: 10.4161/hv.23802

      2. Blutt S E, Miller A D, Salmon S L, Metzger D W, and Conner M E. 2012. IgA is important for clearance and critical for protection from rotavirus infection. Mucosal Immunol, 5: 712-719.
          doi: 10.1038/mi.2012.51

      3. Coffman R L, Sher A, and Seder R A. 2010. Vaccine adjuvants:putting innate immunity to work. Immunity, 4: 492-503.

      4. Demento S L, Siefert A L, Bandyopadhyay A, Sharp F A, and Fahmy T M. 2011. Pathogen-associated molecular patterns on biomaterials:a paradigm for engineering new vaccines. Trends Biotechnol., 29: 294-306.
          doi: 10.1016/j.tibtech.2011.02.004

      5. Dorozhkin S V, and Epple M. 2002. Biological and medical sig-nificance of calcium phosphates. Angew. Chem. Int. Ed., 41: 3130-3146.
          doi: 10.1002/1521-3773(20020902)41:17

      6. Epand R M, and Vogel H J. 1999. Diversity of antimicrobial pep-tides and their mechanisms of action. Biochim. Biophys. Acta, 1462: 11-28.
          doi: 10.1016/S0005-2736(99)00198-4

      7. Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P, Suzuki S, Shaw M H, Kim Y G, and Núñez G. 2012. NLRC4-driven inter-leukin-1β production discriminates between pathogenic and com-mensal bacteria and promotes host intestinal defense. Nat. Immunol., 13: 449-456.
          doi: 10.1038/ni.2263

      8. Frisdal E, Lesnik P, Olivier M, Robillard P, Chapman M J, Huby T, Guerin M, and Le Goff W. 2011. Interleukin-6 protects human macrophages from cellular cholesterol accumulation and attenu-ates the proinflammatory response. J. Biol. Chem., 35: 30926-30936.

      9. Harandi A M, Medaglini D, and Shattock R J. 2010. Vaccine adju-vants:a priority for vaccine research. Vaccine, 28: 2363-2366.
          doi: 10.1016/j.vaccine.2009.12.084

      10. Honko A N, and Mizel S B. 2005. Effects of flagellin on innate and adaptive immunity. Immunol Res, 33: 83-101.
          doi: 10.1385/IR:33:1:083

      11. Klinman D M, Klaschik S, Sato T, and Tross D. 2009. CpG oligo-nucleotides as adjuvants for vaccines targeting infectious diseases. Adv. Drug Deliv. Rev., 61: 248-255.
          doi: 10.1016/j.addr.2008.12.012

      12. Knuschke T, Sokolova V, Rotan O, Wadwa M, Tenbusch M, Han-sen W, Staeheli P, Epple M, Buer J, and Westendorf A M. 2013. Immunization with biodegradable nanoparticles efficiently in-duces cellular immunity and protects against influenza virus in-fection. J. Immunol., 190: 6221-6229.
          doi: 10.4049/jimmunol.1202654

      13. Kozlova D, Chernousova S, Knuschke T, Buer J, Westendorf A M, and Epple M. 2012. Cell targeting by antibody-functionalized calcium phosphate nanoparticles. J. Mater. Chem., 22: 396-404.
          doi: 10.1039/C1JM14683A

      14. Krishnamachari Y, and Salem A K. 2009. Innovative strategies for co-delivering antigens and CpG oligonucleotides. Adv. Drug Deliv. Rev., 61: 205-217.
          doi: 10.1016/j.addr.2008.12.013

      15. Liu F, Yang J, Zhang Y, Zhou D, Chen Y, Gai W, Shi W, Li Q, Tien P, and Yan H. 2010. Recombinant flagellins with partial deletions of the hypervariable domain lose antigenicity but not mucosal adjuvancy. Biochem. Biophys. Res. Commun., 392: 582-587.
          doi: 10.1016/j.bbrc.2010.01.077

      16. Mbow M L, De Gregorio E, Valiante N M, and Rappuoli R. 2010. New adjuvants for human vaccines. Curr. Opin. Immunol., 22: 411-416.
          doi: 10.1016/j.coi.2010.04.004

      17. Miao E A, Andersen-Nissen E, Warren S E, and Aderem A. 2007. TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system. Semin. Immunopathol., 29: 275-288.
          doi: 10.1007/s00281-007-0078-z

      18. Mizel S B, and Bates J T. 2010. Flagellin as an adjuvant: cellular mechanisms and potential. J. Immunol., 185: 5677-5682.
          doi: 10.4049/jimmunol.1002156

      19. Neumann S, Kovtun A, Dietzel I D, Epple M, and Heumann R. 2009. The use of size-defined DNA-functionalized calcium phosphate nanoparticles to minimise intracellular calcium dis-turbance during transfection. Biomaterials, 30: 6794-6802.
          doi: 10.1016/j.biomaterials.2009.08.043

      20. Shi W, Li Y H, Liu F, Yang J Y, Zhou D H, Chen Y Q, Zhang Y, Yang Y, He B X, Han C, Fan M W, and Yan H M. 2012. Flagel-lin enhances saliva IgA response and protection of anti-caries DNA vaccine. J. Dent. Res., 91: 249-254.
          doi: 10.1177/0022034511424283

      21. Sokolova V, Knuschke T, Buer J, Westendorf A M, and Epple M. 2011. Quantitative determination of the composition of multi-shell calcium phosphate-oligonucleotide nanoparticles and their application for the activation of dendritic cells. Acta Biomater., 7: 4029-4036.
          doi: 10.1016/j.actbio.2011.07.010

      22. Sokolova V, Knuschke T, Kovtun A, Buer J, Epple M, and Westendorf A M. 2010. The use of calcium phosphate nanoparti-cles encapsulating toll-like receptor ligands and the antigen he-magglutinin to induce dendritic cell maturation and T cell acti-vation. Biomaterials, 31: 5627-5633.
          doi: 10.1016/j.biomaterials.2010.03.067

      23. Sokolova V, Kozlova D, Knuschke T, Buer J, Westendorf A M, and Epple M. 2013. Mechanism of the uptake of cationic and anionic calcium phosphate nanoparticles by cells. Acta Biomater., 9: 7527-7535.
          doi: 10.1016/j.actbio.2013.02.034

      24. Sokolova V, Rotan O, Klesing J, Nalbant P, Buer J, Knuschke T, Westendorf A M, and Epple M. 2012. Calcium phosphate nano-particles as versatile carrier for small and large molecules across cell membranes. J. Nanopart. Res., 14: 910.
          doi: 10.1007/s11051-012-0910-9

      25. Sun Y, Shi W, Yang J Y, Zhou D H, Chen Y Q, Zhang Y, Yang Y, He B X, Zhong M H, Li Y M, Cao Y, Xiao Y, Li W, Yu J, Li Y H, Fan M W, and Yan H M. 2012. Flagellin-PAc fusion protein is a high-efficacy anti-caries mucosal vaccine. J. Dent. Res., 91: 941-947.
          doi: 10.1177/0022034512457684

      26. Vijay-Kumar M, Carvalho F A, Aitken J D, Fifadara N H, and Gewirtz A T. 2010. TLR5 or NLRC4 is necessary and sufficient for promotion of humoral immunity by flagellin. Eur. J. Immunol., 12: 3528-3534.

      27. Wischke C, Zimmermann J, Wessinger B, Schendler A, Borchert H H, Peters J H, Nesselhut T, and Lorenzen D R. 2009. Poly(I:C) coated PLGA microparticles induce dendritic cell maturation. Int. J. Pharm., 1-2: 61-68.

      28. Yan H, Lamm M E, Björling E, and Huang Y T. 2002. Multiple functions of immunoglobulin A in mucosal defense against vi-ruses: an in vitro measles virus model. J. Virol., 76: 10972-10979.
          doi: 10.1128/JVI.76.21.10972-10979.2002

      29. 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 replace-ment of domains D2 and D3 in flagellin promotes mucosal IgA production and attenuates flagellin-induced inflammatory re-sponse after intranasal immunization. Hum. Vaccin. Immunother., 9: 1084-1092.
          doi: 10.4161/hv.23809

      30. 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).

    • 加载中

    Figures(5) / Tables(1)

    PDF

    Article Metrics

    Article views(6649) PDF downloads(24) Cited by()

    Related
    Proportional views

      Calcium phosphate nanoparticles show an effective activation of the innate immune response in vitro and in vivo after functionalization with flagellin

        Corresponding author: Matthias Epple, matthias.epple@uni-due.de
        Corresponding author: Huimin Yan, hmyan@wh.iov.cn
      • 1. Institute of Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Du isburg-Essen, Essen 45117, Germany
      • 2. Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
      • 3. Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen 45147, Germany
      • Received Date: 17 September 2013
      • Accepted Date: 19 November 2013
      • Published Date: 26 December 2013

      Abstract: 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.

        HTML

      INTRODUCTION