title: Engineered hepatitis B virus surface antigen L protein particles for in vivo active targeting of splenic dendritic cells.
abstract: Dendritic cells (DCs) are key regulators of adaptive T-cell responses. By capturing exogenous antigens and presenting antigen-derived peptides via major histocompatibility complex molecules to naïve T cells, DCs induce antigen-specific immune responses in vivo. In order to induce effective host immune responses, active delivery of exogenous antigens to DCs is considered important for future vaccine development. We recently generated bionanocapsules (BNCs) consisting of hepatitis B virus surface antigens that mediate stringent in vivo cell targeting and efficient endosomal escape, and after the fusion with liposomes (LP) containing therapeutic materials, the BNC-LP complexes deliver them to human liver-derived tissues in vivo. BNCs were further modified to present the immunoglobulin G (IgG) Fc-interacting domain (Z domain) derived from Staphylococcus aureus protein A in tandem. When mixed with IgGs, modified BNCs (ZZ-BNCs) displayed the IgG Fv regions outwardly for efficient binding to antigens in an oriented-immobilization manner. Due to the affinity of the displayed IgGs, the IgG-ZZ-BNC complexes accumulated in specific cells and tissues in vitro and in vivo. After mixing ZZ-BNCs with antibodies against DCs, we used immunocytochemistry to examine which antibodies delivered ZZ-BNCs to mouse splenic DCs following intravenous injection of the ZZ-BNCs. ZZ-BNCs displaying anti-CD11c monoclonal antibodies (α-CD11c-ZZ-BNCs) were found to accumulate with approximately 62% of splenic DCs, and reside within some of them. After the fusion with liposomes containing antigens, the α-CD11c-ZZ-BNCs could elicit the respective antibodies more efficiently than other nontargeting control vaccines, suggesting that this DC-specific nanocarrier is promising for future vaccines.
authors: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors: Hidenori
authors: H
authors: Matsuo
authors: Nobuo
authors: N
authors: Yoshimoto
authors: Masumi
authors: M
authors: Iijima
authors: Tomoaki
authors: T
authors: Niimi
authors: Joohee
authors: J
authors: Jung
authors: Seong-Yun
authors: SY
authors: Jeong
authors: Eun Kyung
authors: EK
authors: Choi
authors: Tomomitsu
authors: T
authors: Sewaki
authors: Takeshi
authors: T
authors: Arakawa
authors: Shun'ichi
authors: S
authors: Kuroda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics; D003713:Dendritic Cells / Q000378:metabolism*; D004664:Encephalitis Virus, Japanese / Q000276:immunology; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D013154:Spleen / Q000166:cytology; D013205:Staphylococcal Protein A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D001428:Bacterial Vaccines; D006514:Hepatitis B Surface Antigens; C096362:L protein, hepatitis B virus; D008081:Liposomes; D053769:Nanocapsules; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; D014759:Viral Envelope Proteins; D014764:Viral Proteins