title: Lipid nanocapsule as vaccine carriers for his-tagged proteins: evaluation of antigen-specific immune responses to HIV I His-Gag p41 and systemic inflammatory responses.
abstract: The purpose of this study was to design novel nanocapsules (NCs) with surface-chelated nickel (Ni-NCs) as a vaccine delivery system for histidine (His)-tagged protein antigens. Ni-NCs were characterized for binding His-tagged model proteins through high-affinity non-covalent interactions. The mean diameter and zeta potential of the optimized Ni-NCs were 214.9 nm and -14.8 mV, respectively. The optimal binding ratio of His-tagged Green Fluorescent Protein (His-GFP) and His-tagged HIV-1 Gag p41 (His-Gag p41) to the Ni-NCs was 1:221 and 1:480 w/w, respectively. Treatment of DC2.4 cells with Ni-NCs did not result in significant loss in the cell viability up to 24h (<5%). We further evaluated the antibody response of the Ni-NCs using His-Gag p41 as a model antigen. Formulations were administered subcutaneously to BALB/c mice at day 0 (prime) and 14 (boost) followed by serum collection on day 28. Serum His-Gag p41-specific antibody levels were found to be significantly higher at 1 and 0.5 μg doses of Gag p41-His-Ni-NCs (His-Gag p41 equivalent) compared with His-Gag p41 (1 μg) adjuvanted with aluminum hydroxide (AH). The serum IgG2a levels induced by Gag p41-His-Ni-NCs (1 μg) were significantly higher than AH adjuvanted His-Gag p41. The Ni-NCs alone did not result in the elevation of systemic IL-12/p40 and CCL5/RANTES inflammatory cytokine levels upon subcutaneous administration in BALB/c mice. In conclusion, the proposed Ni-NCs can bind His-tagged proteins and have the potential to be used as antigen delivery system capable of generating strong antigen-specific antibodies at doses much lower than with aluminum-based adjuvant and causing no significant elevation of systemic pro-inflammatory IL-12/p40 and CCL5/RANTES cytokines.
authors: Division of Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7355, United States.
authors: Saurabh
authors: S
authors: Wadhwa
authors: Anekant
authors: A
authors: Jain
authors: Jerold G
authors: JG
authors: Woodward
authors: Russell J
authors: RJ
authors: Mumper
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000276:immunology; D006639:Histidine / Q000737:chemistry*; D007249:Inflammation / Q000276:immunology; D007279:Injections, Subcutaneous; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules; D009532:Nickel / Q000737:chemistry; D010316:Particle Size; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000941:Antigens; D016207:Cytokines; D008055:Lipids; D053769:Nanocapsules; D014612:Vaccines; D054301:gag Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; D006639:Histidine; D009532:Nickel