title: A simple approach for enhanced immune response using engineered dendritic cell targeted nanoparticles.
abstract: In this study, we demonstrate a simple strategy for enhanced immune response using a two-component dendritic cell (DC) targeted antigen delivery system. One component consists of a recombinant bifunctional fusion protein (bfFp) used for DC targeting, whereas, the other component is made of biotinylated PLGA nanoparticles that encapsulate the antigen. The fusion protein (bfFp) made of a truncated core-streptavidin fused to anti-DEC-205 single chain antibody (scFv) was mixed with ovalbumin-loaded biotinylated NPs that were formulated using biotin-PEG (2000)-PLGA, and the combination, bfFp functionalized NPs was used for DC targeted antigen delivery. In vitro DC uptake studies revealed a 2-fold higher receptor-mediated uptake of bfFp functionalized NPs when compared to non-targeted NPs. Immunization of the mice with the bfFp functionalized NPs in conjunction with DC maturation stimulus (anti-CD40 mAb) enhanced OVA-specific IgG and IgG subclass responses. Splenocytes of these mice secreted significantly higher levels of Th1 (IFN-γ and IL-2) cytokines upon ex vivo restimulation with OVA. The promising outcomes of the bfFp functionalized DC targeted system support its use as a versatile vaccine delivery system for the design of monovalent or polyvalent vaccines.
authors.affiliation: University of Alberta, Edmonton, Alberta, Canada, T6G 2N8.
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Raghuwanshi
authors.forename: Vivek
authors.initials: V
authors.lastname: Mishra
authors.forename: Mavanur R
authors.initials: MR
authors.lastname: Suresh
authors.forename: Kamaljit
authors.initials: K
authors.lastname: Kaur
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004337:Drug Carriers / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D053758:Nanoparticles; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000276:immunology
chemical_list: D000941:Antigens; D016207:Cytokines; D004337:Drug Carriers; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D010047:Ovalbumin