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. 2015 Mar 10;10(3):e0117203.
doi: 10.1371/journal.pone.0117203. eCollection 2015.

Non-carrier nanoparticles adjuvant modular protein vaccine in a particle-dependent manner

Arjun Seth  1 , Fiona K Ritchie  1 , Nani Wibowo  1 , Linda H L Lua  2 , Anton P J Middelberg  1
Affiliations

Non-carrier nanoparticles adjuvant modular protein vaccine in a particle-dependent manner

Arjun Seth et al. PLoS One. .

Abstract

Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH), poly (D,L-lactic-co-glycolic acid) (PLGA) and poly caprolactone (PCL) nanoparticles (nps) to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e) was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing). In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties.

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Conflict of interest statement

Competing Interests: Authors NW, LL, and APJM are named contributors to a patent related to the use of nanoparticles in vaccines, filed by the University of Queensland. By virtue of their employment they may receive financial benefit if the University’s commercialisation company delivers a commercial return to the University from the patent.

Figures

Fig 1
Fig 1. TEM images of nanoparticles A) silica, B) PLGA, C) PCL, D) amine functionalized silica and E) pegylated silica.
Scale bar is 100 nm.
Fig 2
Fig 2. Percentage of protein mass (CapM2e) in supernatant after mixing with different nanoparticle solutions.
Fig 3
Fig 3. M2e-specific antibody titers in BALB/c mice following three subcutaneous immunizations with different formulations.
A) Total IgG, B) IgG1, and C) IgG2a. *, p<0.05; **, p<0.01; ***, p<0.001; ns = not significant.
Fig 4
Fig 4. Determination of IFNγ response in splenocytes.
M2e-specific T-cell response was evaluated by measuring IFNγ secreting cells by enzyme-linked immunospot (ELISPOT). A) Carrier (wt VP1)-specific, B) M2e-specific, C) positive control (Concanavalin A (Con A)). No significant difference was observed between the mean value of each group (p>0.05).
Fig 5
Fig 5. M2e-specific IgG1 titer in BALB/c mice following three subcutaneous immunizations with different formulations.
*, p<0.05; **, p<0.01; ***, p<0.001; ns = not significant.
See this image and copyright information in PMC

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Grants and funding

Funding for this study was provided by the Queensland State Government in the form of a Premier’s Fellowship to APJM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript