Abstract
Mesoporous silica nanoparticles have drawn increasing attention as promising candidates in vaccine delivery. Previous studies evaluating silica-based vaccine delivery systems concentrated largely on macromolecular antigens, such as inactivated whole viruses. In this study, we synthesized dendritic mesoporous silica nanoparticles (DMSNs), and we evaluated their effectiveness as delivery platforms for peptide-based subunit vaccines. We encapsulated and tested in vivo an earlier reported foot-and-mouth disease virus (FMDV) peptide vaccine (B2T). The B2T@DMSNs formulation contained the peptide vaccine and the DMSNs without further need of other compounds neither adjuvants nor emulsions. We measured in vitro a sustained release up to 930 h. B2T@DMSNs-57 and B2T@DMSNs-156 released 23.7% (135 µg) and 22.8% (132 µg) of the total B2T. The formation of a corona of serum proteins around the DMSNs increased the B2T release up to 61% (348 µg/mg) and 80% (464 µg/mg) for B2T@DMSNs-57 and B2T@DMSNs-156. In vitro results point out to a longer sustained release, assisted by the formation of a protein corona around DMSNs, compared to the reference formulation (i.e., B2T emulsified in Montanide). We further confirmed in vivo immunogenicity of B2T@DMSNs in a particle size-dependent manner. Since B2T@DMSNs elicited specific immune responses in mice with high IgG production like the reference B2T@Montanide™, self-adjuvant properties of the DMSNs could be ascribed. Our results display DMSNs as efficacious nanocarriers for peptide-based vaccine administration.
Highlights
Peptide-based vaccines are considered an attractive alternative strategy to overcome many of the limitations of conventional whole virus-based vaccines [1,2,3]
DLS measurements indicated that the averaged hydrodynamic diameter of dendritic mesoporous silica nanoparticles (DMSNs)-57 was 75 nm with a polydispersity index (PDI) of 0.060 and the averaged hydrodynamic diameter of DMSNs-156 was 227 nm with a PDI of 0.061 (Figure 1C; §SI1.1, Figure SI-1.E)
Our results demonstrate that DMSNs are colloidally stable and monodisperse, with high loading capacities for a bioactive peptide such as B2T, besides being reported as non-toxic [53,54,55,56]
Summary
Peptide-based vaccines are considered an attractive alternative strategy to overcome many of the limitations of conventional (inactivated, attenuated) whole virus-based vaccines [1,2,3] They present advantages such as reduced toxicity, good definition of T- and B-cell epitopes for targeted immune responses, cost-effective scale up manufacturing processes, easy handling, storage, and transport [1, 4, 5]. Adjuvants of different kinds, such as aluminum hydroxide, mineral salts, water-oil emulsions, or liposome-based formulations have been developed to enhance efficacy [7] These strategies can boost to a certain extent the low immunogenicity of peptidebased vaccines, only a limited number are approved for human and animal applications due to their not well-established mode of action, as well as to other related toxicity and safety issues [8, 9]
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