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  • Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

PloS one (2014-12-02)
Dace Skrastina, Ivars Petrovskis, Ilva Lieknina, Janis Bogans, Regina Renhofa, Velta Ose, Andris Dishlers, Yuri Dekhtyar, Paul Pumpens
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.

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Sodium carbonate, anhydrous, powder, 99.999% trace metals basis
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Urea-12C, 99.9 atom % 12C
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Sodium carbonate, BioXtra, ≥99.0%
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Phenylmethanesulfonyl fluoride, ≥98.5% (GC)
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Mouse Monoclonal Antibody Isotyping Reagents, sufficient for 1000 tests (clones) (by ELISA), sufficient for 40 tests (clones) (by immunodiffusion, ODD)
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4100025-250MG250 mg
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Urea solution, 40 % (w/v) in H2O
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Sodium carbonate, reference material for titrimetry, certified by BAM, >99.5%
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4100025-250MG250 mg
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Phenylmethanesulfonyl fluoride, ≥99.0% (T)
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4100025-250MG250 mg
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Sodium carbonate, BioUltra, anhydrous, ≥99.5% (calc. on dry substance, T)
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4100025-250MG250 mg
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Urea solution, BioUltra, ~8 M in H2O
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Sodium carbonate, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.5%
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Sodium carbonate, ACS reagent, anhydrous, ≥99.5%, powder or granules
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Sodium carbonate, ACS reagent (primary standard), anhydrous, 99.95-100.05% dry basis
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4100025-250MG250 mg
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Sodium carbonate, powder, ≥99.5%, ACS reagent
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Sodium carbonate, ReagentPlus®, ≥99.5%
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Urea solution, suitable for microbiology, 40% in H2O
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Urea, BioXtra, pH 7.5-9.5 (20 °C, 5 M in H2O)
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4100025-250MG250 mg
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Urea, ACS reagent, 99.0-100.5%
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Urea, powder, BioReagent, for molecular biology, suitable for cell culture
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Urea, ReagentPlus®, ≥99.5%, pellets
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Urea, meets USP testing specifications
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Urea, suitable for electrophoresis
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Urea, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99%
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Urea, puriss., meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%, 99.0-101.0% (calc. on dry substance)
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Urea, European Pharmacopoeia (EP) Reference Standard
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Sodium carbonate concentrate, 0.1 M Na2CO3 in water, eluent concentrate for IC
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4100025-250MG250 mg
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Sodium carbonate-12C, 99.9 atom % 12C
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Urea, analytical standard
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