Mesoporous Silica Nanoparticles Act as a Self‐Adjuvant for Ovalbumin Model Antigen in Mice

Abstract

Immunization to the model protein antigen ovalbumin (OVA) is investigated using MCM-41 mesoporous silica nanoparticles as a novel vaccine delivery vehicle and adjuvant system in mice. The effects of amino surface functionalization and adsorption time on OVA adsorption to nanoparticles are assessed. Amino-functionalized MCM-41 (AM-41) shows an effect on the amount of OVA binding, with 2.5-fold increase in binding capacity (72 mg OVA/g AM-41) compared to nonfunctionalized MCM-41 (29 mg OVA/g MCM-41). Immunization studies in mice with a 10 μg dose of OVA adsorbed to AM-41 elicits both antibody and cell-mediated immune responses following three subcutaneous injections. Immunizations at a lower 2 μg dose of OVA adsorbed to AM-41 particles results in an antibody response but not cell-mediated immunity. The level of antibody responses following immunization with nanoformulations containing either 2 μg or 10 μg of OVA are only slightly lower than that in mice which receive 50 μg OVA adjuvanted with QuilA, a crude mixture of saponins extracted from the bark of the Quillaja saponaria Molina tree. This is a significant result, since it demonstrates that AM-41 nanoparticles are self-adjuvanting and elicit immune responses at reduced antigen doses in vivo compared to a conventional delivery system. Importantly, there are no local or systemic negative effects in animals injected with AM-41. Histopathological studies of a range of tissue organs show no changes in histopathology of the animals receiving nanoparticles over a six week period. These results establish the biocompatible MCM-41 silica nanoparticles as a new method for vaccine delivery which incorporates a self-adjuvant effect.

Effects of 3D nanocomposite bioceramic scaffolds on the immune response

“…However, there were no local or systemic negative effects in animals injected with AM-41. 48 In the present study, MGHA scaffolds do not stimulate a significant inflammatory response in vitro.…”

Mesoporous Silica Nanoparticles with Large Pores for the Encapsulation and Release of Proteins

“…MSNs have exhibited potential as a non-invasive and biocompatible platform for protein delivery, [26][27][28] especially in the fields of enzyme therapies, 9-10 vaccination, [7][8]29 and imaging. 30 Since MSNs are much smaller than eukaryotic cells, they can facilitate the transport of proteins into the cytosol via an endocytosis pathway and subsequent endosomal escape.…”

“…[37][38] Typically, proteins are only adsorbed onto the external surface of MSNs due to the small pore diameter (< 3 nm) preventing the proteins from entering the MSNs' interior pores. 7,39 Proteins adsorbed at the MSNs' outer surface do not make use of the protective environment inside the MSNs, nor do they utilize the large internal surface area presented by the pores. 16,40 Thus, limitations in generating small (< 200 nm in diameter) MSNs with sufficient pore sizes (> 5 nm) to encapsulate proteins or other biomacromolecules is one of the major hurdles for "comfortably" hosting large molecules.…”

Fabrication of nanoadjuvant with poly-e-caprolactone (PCL) for developing a single-shot vaccine providing prolonged immunity

“…19 The past decade has seen important developments in the use of nanotechnology in the field of vaccine adjuvants and carrier vehicles, especially polymeric materials in the nano-and microranges. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] These studies hold great promise to elicit complex immune responses from all branches of immunity for effective and safe vaccination against major infections that have escaped effective vaccination.…”