Targeting and activation of antigen-specific B-cells by calcium phosphate nanoparticles loaded with protein antigen.
Cross-linking of the B-cell receptors of an antigen-specific B-cell is the initial signal for B-cell activation, proliferation, and differentiation into antibody secreting plasma cells. Since multivalent particulate structures are efficient activators of antigen-specific B-cells, we developed biodegradable calcium phosphate nanoparticles displaying protein antigens on their surface and explored the efficacy of the B-cell activation after exposure to these nanoparticles. The calcium phosphate nanoparticles were functionalized with the model antigen Hen Egg Lysozyme (HEL) to take advantage of a HEL-specific B-cell receptor transgenic mouse model. The nanoparticles were characterized by scanning electron microscopy and dynamic light scattering. The functionalized calcium phosphate nanoparticles were preferentially bound and internalized by HEL-specific B-cells. Co-cultivation of HEL-specific B-cells with the functionalized nanoparticles also increased surface expression of B-cell activation markers. Functionalized nanoparticles were able to effectively cross-link B-cell receptors at the surface of antigen-matched B-cells and were 100-fold more efficient in the activation of B-cells than soluble HEL. Thus, calcium phosphate nanoparticles coated with protein antigens are promising vaccine candidates for induction humoral immunity.
Department of Molecular and Medical Virology, Ruhr-University Bochum, Universitaetsstr. 150, D-44780 Bochum, Germany. Electronic address: temchura@yandex.com.
Vladimir V
VV
Temchura
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, D-45117 Essen, Germany.
Diana
D
Kozlova
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, D-45117 Essen, Germany.
Viktoriya
V
Sokolova
Department of Molecular and Medical Virology, Ruhr-University Bochum, Universitaetsstr. 150, D-44780 Bochum, Germany.
Klaus
K
Uberla
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Universitaetsstr. 5-7, D-45117 Essen, Germany.
Matthias
M
Epple
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002130:Calcium Phosphates / Q000737:chemistry*; D002478:Cells, Cultured; D056724:Immunity, Humoral / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
D002130:Calcium Phosphates; D053769:Nanocapsules; D011947:Receptors, Antigen, B-Cell; C020243:calcium phosphate; C421864:hen egg lysozyme; D009113:Muramidase
B-cell activation; Calcium phosphate; Cell targeting; Nanoparticles