title: Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.
abstract: Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm) with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs) formed by recombinant full-length Hepatitis B virus core (HBc) protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL) led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Dace
authors.initials: D
authors.lastname: Skrastina
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Ivars
authors.initials: I
authors.lastname: Petrovskis
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Ilva
authors.initials: I
authors.lastname: Lieknina
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Janis
authors.initials: J
authors.lastname: Bogans
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Regina
authors.initials: R
authors.lastname: Renhofa
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Velta
authors.initials: V
authors.lastname: Ose
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Andris
authors.initials: A
authors.lastname: Dishlers
authors.affiliation: Institute of Biomedical Engineering and Nanotechnologies, Riga Technical University, Riga, Latvia.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Dekhtyar
authors.affiliation: Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Paul
authors.initials: P
authors.lastname: Pumpens
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology / Q000494:pharmacology; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006512:Hepatitis B Core Antigens / Q000276:immunology / Q000494:pharmacology*; D017325:Hepatitis B Vaccines / Q000276:immunology / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000276:immunology*; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D008055:Lipids / Q000276:immunology / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D008050:Lipid A; D008055:Lipids; C114843:incomplete Freund's adjuvant; C041524:aluminum sulfate; D012822:Silicon Dioxide; D005620:Freund's Adjuvant; C048436:monophosphoryl lipid A