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Silica Nanoparticles as the Adjuvant for the Immunisation of Mice Using Hepatitis B Core Virus-Like Particles

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      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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      Most cited references 54

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            Author and article information

            [1 ]Latvian Biomedical Research and Study Centre, Riga, Latvia
            [2 ]Institute of Biomedical Engineering and Nanotechnologies, Riga Technical University, Riga, Latvia
            Academia Sinica, Taiwan
            Author notes

            Competing Interests: The authors have declared that no competing interests exist.

            Conceived and designed the experiments: PP DS. Performed the experiments: DS IL IP JB VO RR. Analyzed the data: DS PP IP VO YD. Contributed reagents/materials/analysis tools: IL DS JB VO. Wrote the paper: DS PP AD.

            Role: Editor
            PLoS One
            PLoS ONE
            PLoS ONE
            Public Library of Science (San Francisco, USA )
            1 December 2014
            : 9
            : 12
            25436773 4250084 PONE-D-14-41450 10.1371/journal.pone.0114006

            This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

            Pages: 17
            This work was supported by ERDF 2013/0053/2DP/ ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Research Article
            Biology and Life Sciences
            Immune Response
            Antibody Response
            Vaccination and Immunization
            Immunologic Adjuvants
            Molecular Biology
            Engineering and Technology
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            The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.



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