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.

Synthetic Lipoteichoic Acid Glycans Are Potential Vaccine Candidates to Protect from Clostridium difficile Infections

“…Therefore, we quantitatively determined adsorption of 4 to alum with two in vitro methods. In a modified assay described by Skrastina et al (2014), alum was mixed with 4 in PBS and incubated at 4 C for up to 24 hr. The concentration of non-adsorbed protein was used to calculate adsorption efficiencies in percent ( Figure 5A).…”

Thickness and Sphericity Control of Hollow Hard Silica Shells through Iron (III) Doping: Low Threshold Ultrasound Contrast Agents

“…The aforementioned advantages for these new ultrathin asymmetric Fe(III)‐SiO 2 shells, such as prolonged persistency and easy visualization, are important in promoting a mature immune response and designing immunotherapy strategies, respectively . Since silica nanoparticles have been previously reported to be a strong immune adjuvant that amplify antibody production and elicit immunological protection response, it is hypothesized that these new Fe(III)‐SiO 2 2 µm shells can also effectively activate immune response while being able to generate stable ultrasound signals for tracking the adjuvant location. To test their adjuvanticity, innate immune cells, macrophages RAW264.7, primed with LPS were incubated with shells and IL‐1β in the supernatant was measured by enzyme‐linked immunosorbent assay (ELISA) to assess the activation level of macrophages.…”

Hollow mesoporous silica nanoparticles as delivery vehicle of foot‐and‐mouth disease virus‐like particles induce persistent immune responses in guinea pigs

“…Through the BJH method, the pore and aperture sizes of the HMSNs were found to be 0.57 cm 3 /g and 22.07 Å (approximately 2.2 nm), respectively. These unique structural characteristics determined the HMSNs' strong adsorption capacity 31,32. Adsorption kinetic experiments indicated that the adsorption capacity of the HMSNs reached up to 300 μg/mg (VLPs/HMSNs).This result may be dependent on the large surface area of HMSNs and the high-density charge distribution on the VLPs surface.…”