Nanoparticle-based B-cell targeting vaccines: Tailoring of humoral immune responses by functionalization with different TLR-ligands.
Induction of an appropriate type of humoral immune response during vaccination is essential for protection against viral and bacterial infections. We recently observed that biodegradable calcium phosphate (CaP) nanoparticles coated with proteins efficiently targeted and activated naïve antigen-specific B-cells in vitro. We now compared different administration routes for CaP-nanoparticles and demonstrated that intramuscular immunization with such CaP-nanoparticles induced stronger immune responses than immunization with monovalent antigen. Additional functionalization of the CaP-nanoparticles with TRL-ligands allowed modulating the IgG subtype response and the level of mucosal IgA antibodies. CpG-containing CaP-nanoparticles were as immunogenic as a virus-like particle vaccine. Functionalization of CaP-nanoparticles with T-helper cell epitopes or CpG also allowed overcoming lack of T-cell help. Thus, our results indicate that CaP-nanoparticle-based B-cell targeting vaccines functionalized with TLR-ligands can serve as a versatile platform for efficient induction and modulation of humoral immune responses in vivo.
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany.
Claudia
C
Zilker
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Essen, Germany.
Diana
D
Kozlova
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Essen, Germany.
Viktoriya
V
Sokolova
Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Huimin
H
Yan
Inorganic Chemistry and Center for Nanointegration Duisburg-Essen (CeNIDE), University of Duisburg-Essen, Essen, Germany.
Matthias
M
Epple
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany; University Hospital Erlangen, Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Klaus
K
Überla
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany; University Hospital Erlangen, Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany. Electronic address: temchura@yandex.com.
Vladimir
V
Temchura
D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002130:Calcium Phosphates / Q000737:chemistry; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007273:Injections, Intramuscular; D008024:Ligands; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*
D000941:Antigens; D002130:Calcium Phosphates; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D051193:Toll-Like Receptors; D058425:Vaccines, Virus-Like Particle; C020243:calcium phosphate; C421864:hen egg lysozyme; D009113:Muramidase
B-cell activation; Calcium phosphate; Nanoparticles; TLR ligands