Mesoporous ZnO nanocapsules for the induction of enhanced antigen-specific immunological responses

Abstract

The application of nanotechnology in vaccinology has fuelled rapid advancement towards the design and development of nanovaccines. Nanoparticles have been found to enhance vaccine efficacy through the spatiotemporal orchestration of antigen delivery to secondary lymphoid organs and antigen-presentation by Antigen Presenting Cells (APCs) synchronized with stimulation of innate and adaptive immune responses. Metal based nanoparticles (MNPs) have been extensively engineered for the generation of nanovaccines owing to their intrinsic adjuvant-like properties and immunomodulatory functions. Furthermore, mesoporous nanocapsules of late have attracted researchers due to their precise size and exclusive capacity to encapsulate a wide range of biomolecules and their sustained release at the targeted sites. Herein, we have designed a novel mesoporous ZnO nanocapsule (mZnO) having a size of ∼12 nm with an average pore diameter of 2.5 nm, using a surfactant-free sonochemical method and investigated its immunomodulatory properties by using Ova loaded mZnO nanocapsules [mZnO(Ova)] in a mice model. Our findings show that mZnO(Ova) administration steered the enhanced expansion of antigen-specific T-cells and induction of IFN-γ producing effector CD4⁺ and CD8⁺ T-cells. Also, antigen-specific IgG levels were enriched in both the serum and lymph nodes of mZnO(Ova) immunized mice. Further, we noticed a substantial increase in serum IgG2a or IgG2b levels and IFN-γ secretion in Ova restimulated splenocytes from mZnO(Ova) immunized mice, indicating that mZnO(Ova) skew Th1 type immune response. Overall, the uniqueness of mZnO nanocapsules in terms of the defined particle to pore numbers ratio (maximum of three cavities per particle) allows loading antigens efficiently. Given these features in combination with its immunomodulatory characteristics reinforces the idea that mZnO could be used as an effective antigen-adjuvant platform for the development of novel nano-based vaccines against multiple diseases.