Nanoparticle-based B-cell targeting vaccines: Tailoring of humoral immune responses by functionalization with different TLR-ligands

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• 作者：Claudia Zilker^a ; Diana Kozlova ; Dr^b ; Viktoriya Sokolova ; Dr^b ; Huimin Yan ; Dr^c ; Matthias Epple ; Dr^b ; Klaus Ü ; berla ; MD^a ; ^d ; Vladimir Temchura ; Dr^a ; ^d ; ^{temchura@yandex.com}
• 关键词：Calcium phosphate ; Nanoparticles ; B-cell activation ; TLR ligands
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：13
• 期：1
• 页码：173-182
• 全文大小：1275 K
• 卷排序：13

文摘

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.